Subjects -> MEDICAL SCIENCES (Total: 8690 journals)
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    - MEDICAL SCIENCES (2415 journals)
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MEDICAL SCIENCES (2415 journals)            First | 3 4 5 6 7 8 9 10 | Last

Showing 1201 - 1400 of 3562 Journals sorted alphabetically
Journal of Evaluation In Clinical Practice     Hybrid Journal   (Followers: 6)
Journal of Evidence-Based Healthcare     Open Access   (Followers: 1)
Journal of Evidence-Based Integrative Medicine     Open Access   (Followers: 18)
Journal of Evidence-Based Medicine     Partially Free   (Followers: 4)
Journal of Exercise Science & Fitness     Open Access   (Followers: 29)
Journal of Experimental and Clinical Anatomy     Open Access   (Followers: 2)
Journal of Family and Community Medicine     Open Access   (Followers: 3)
Journal of Family Medicine and Primary Care     Open Access   (Followers: 11)
Journal of Foot and Ankle Research     Open Access   (Followers: 6)
Journal of Forensic Science and Research     Open Access   (Followers: 2)
Journal of Gandaki Medical College-Nepal     Open Access  
Journal of Generic Medicines     Hybrid Journal   (Followers: 2)
Journal of Geographical Sciences     Hybrid Journal   (Followers: 1)
Journal of Global Antimicrobial Resistance     Hybrid Journal   (Followers: 3)
Journal of Hand Therapy     Hybrid Journal   (Followers: 19)
Journal of Head & Neck Physicians and Surgeons     Open Access   (Followers: 2)
Journal of Health & Medical Informatics     Open Access   (Followers: 62)
Journal of Health and Biological Sciences     Open Access   (Followers: 1)
Journal of Health Design     Open Access   (Followers: 1)
Journal of Health Economics and Outcomes Research     Open Access   (Followers: 1)
Journal of Health Promotion and Behavior     Open Access  
Journal of Health Research and Reviews     Open Access  
Journal of Health Science and Medical Research     Open Access  
Journal of Health Science Research     Open Access  
Journal of Health Sciences     Open Access   (Followers: 1)
Journal of health sciences     Open Access  
Journal of Health Sciences / Sağlık Bilimleri Dergisi     Open Access  
Journal of Health Sciences and Medicine     Open Access  
Journal of Health Sciences and Medicine     Open Access   (Followers: 6)
Journal of Health Sciences and Surveillance System     Open Access  
Journal of Health Sciences Scholarship     Open Access  
Journal of Health Specialties     Open Access  
Journal of Health Studies     Open Access  
Journal of Healthcare Informatics Research     Hybrid Journal   (Followers: 1)
Journal of Heavy Metal Toxicity and Diseases     Open Access  
Journal of Helminthology     Hybrid Journal   (Followers: 2)
Journal of Herbs Spices & Medicinal Plants     Hybrid Journal  
Journal of HIV for Clinical and Scientific Research     Open Access   (Followers: 2)
Journal of Hospital Medicine     Hybrid Journal   (Followers: 11)
Journal of Huazhong University of Science and Technology [Medical Sciences]     Hybrid Journal  
Journal of Human Hypertension     Hybrid Journal   (Followers: 3)
Journal of Human Rhythm     Open Access  
Journal of Human Transcriptome     Open Access  
Journal of Ideas in Health     Open Access  
Journal of Inflammation     Open Access   (Followers: 2)
Journal of Inflammation Research     Open Access  
Journal of Injury and Violence Research     Open Access   (Followers: 6)
Journal of Innovation in Health Informatics     Open Access   (Followers: 17)
Journal of Institute of Medicine     Open Access  
Journal of Insulin Resistance     Open Access   (Followers: 1)
Journal of Interactional Research in Communication Disorders     Hybrid Journal   (Followers: 5)
Journal of Interferon & Cytokine Research     Hybrid Journal   (Followers: 3)
Journal of International Medical Research     Open Access   (Followers: 3)
Journal of Interventional Medicine     Open Access   (Followers: 1)
Journal of Investigative Medicine     Hybrid Journal   (Followers: 3)
Journal of Islamabad Medical & Dental College     Open Access   (Followers: 2)
Journal of Istanbul Faculty of Medicine     Open Access  
Journal of Karnali Academy of Health Sciences     Open Access   (Followers: 1)
Journal of Kathmandu Medical College     Open Access   (Followers: 1)
Journal of King Abdulaziz University : Medical Sciences     Open Access   (Followers: 2)
Journal of Laboratory Medicine     Hybrid Journal   (Followers: 27)
Journal of Laryngology and Voice     Open Access   (Followers: 11)
Journal of Lasers in Medical Sciences     Open Access  
Journal of Law, Medicine & Ethics     Hybrid Journal   (Followers: 28)
Journal of Legal Medicine     Hybrid Journal   (Followers: 7)
Journal of Limb Lengthening & Reconstruction     Open Access  
Journal of Lumbini Medical College     Open Access   (Followers: 1)
Journal of Mahatma Gandhi Institute of Medical Sciences     Open Access  
Journal of Manipulative and Physiological Therapeutics     Hybrid Journal   (Followers: 6)
Journal of Manmohan Memorial Institute of Health Sciences     Open Access   (Followers: 1)
Journal of Marine Medical Society     Open Access  
Journal of Materials Science : Materials in Medicine     Hybrid Journal   (Followers: 4)
Journal of Maternal and Child Health     Open Access  
Journal of Mechanics in Medicine and Biology     Hybrid Journal  
Journal of Medical and Biological Engineering     Hybrid Journal   (Followers: 4)
Journal of Medical and Biomedical Sciences     Open Access   (Followers: 2)
Journal of Medical Case Reports     Open Access   (Followers: 1)
Journal of Medical Cases     Open Access   (Followers: 6)
Journal of Medical Colleges of PLA     Full-text available via subscription  
Journal of Medical Disorders     Open Access  
Journal of Medical Economics     Hybrid Journal   (Followers: 8)
Journal of Medical Education and Curricular Development     Open Access   (Followers: 6)
Journal of Medical Ethics     Partially Free   (Followers: 27)
Journal of Medical Ethics and History of Medicine     Open Access   (Followers: 19)
Journal of Medical Humanities     Hybrid Journal   (Followers: 21)
Journal of Medical Hypotheses and Ideas     Open Access  
Journal of Medical Imaging and Health Informatics     Full-text available via subscription   (Followers: 1)
Journal of Medical Investigation and Practice     Open Access  
Journal of Medical Laboratory and Diagnosis     Open Access  
Journal of Medical Law and Ethics     Full-text available via subscription   (Followers: 17)
Journal of Medical Microbiology     Full-text available via subscription   (Followers: 6)
Journal of Medical Sciences     Open Access  
Journal of Medical Sciences     Open Access  
Journal of Medical Screening     Hybrid Journal   (Followers: 6)
Journal of Medical Signals and Sensors     Open Access   (Followers: 3)
Journal of Medical Society     Open Access  
Journal of Medical Systems     Hybrid Journal  
Journal of Medical Toxicology     Hybrid Journal   (Followers: 6)
Journal of Medical Ultrasound     Open Access   (Followers: 2)
Journal of Medicinal Botany     Open Access  
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 208)
Journal of Medicine     Open Access   (Followers: 1)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Medicine and Philosophy     Hybrid Journal   (Followers: 9)
Journal of Medicine and the Person     Hybrid Journal  
Journal of Medicine in Scientific Research     Open Access  
Journal of Medicine in the Tropics     Open Access  
Journal of Medicine Research and Development     Open Access   (Followers: 3)
Journal of Medicine, Physiology and Biophysics     Open Access   (Followers: 5)
Journal of Medicines Development Sciences     Open Access   (Followers: 1)
Journal of Metabolomics & Systems Biology     Open Access   (Followers: 2)
Journal of Mind and Medical Sciences     Open Access   (Followers: 1)
Journal of Molecular Medicine     Hybrid Journal   (Followers: 11)
Journal of Movement Disorders     Open Access   (Followers: 2)
Journal of Multidisciplinary Research in Healthcare     Open Access   (Followers: 3)
Journal of Muscle Research and Cell Motility     Hybrid Journal   (Followers: 1)
Journal of Nanotechnology in Engineering and Medicine     Full-text available via subscription   (Followers: 6)
Journal of Nanotheranostics     Open Access   (Followers: 1)
Journal of Natural Medicines     Hybrid Journal  
Journal of Natural Science, Biology and Medicine     Open Access   (Followers: 3)
Journal of Nature and Science of Medicine     Open Access   (Followers: 4)
Journal of Negative and No Positive Results     Open Access  
Journal of Nepalgunj Medical College     Open Access  
Journal of Neurocritical Care     Open Access  
Journal of Neurodegenerative Diseases     Open Access   (Followers: 2)
Journal of Neurorestoratology     Open Access  
Journal of Neuroscience and Neurological Disorders     Open Access  
Journal of Nobel Medical College     Open Access  
Journal of Obesity and Bariatrics     Open Access   (Followers: 2)
Journal of Occupational Health     Open Access  
Journal of Occupational Therapy Education     Open Access   (Followers: 12)
Journal of Ocular Biology, Diseases, and Informatics     Hybrid Journal  
Journal of Oral Biology and Craniofacial Research     Full-text available via subscription  
Journal of Oral Health and Craniofacial Science     Open Access  
Journal of Orofacial Sciences     Open Access  
Journal of Otorhinolaryngology, Hearing and Balance Medicine     Open Access   (Followers: 1)
Journal of Ovarian Research     Open Access  
Journal of Ozone Therapy     Open Access  
Journal of Palliative Medicine     Hybrid Journal   (Followers: 47)
Journal of Paramedical Sciences & Rehabilitation     Open Access  
Journal of Parkinsonism and Restless Legs Syndrome     Open Access   (Followers: 2)
Journal of Parkinson’s Disease and Alzheimer’s Disease     Open Access   (Followers: 1)
Journal of Participatory Medicine     Open Access  
Journal of Patan Academy of Health Sciences     Open Access  
Journal of Pathogens     Open Access   (Followers: 1)
Journal of Patient Experience     Open Access  
Journal of Patient Safety and Risk Management     Hybrid Journal   (Followers: 2)
Journal of Patient-Centered Research and Reviews     Open Access  
Journal of Patient-Reported Outcomes     Open Access  
Journal of Periodontal Research     Hybrid Journal  
Journal of Personalized Medicine     Open Access   (Followers: 3)
Journal of Pest Science     Hybrid Journal   (Followers: 1)
Journal of Pharmaceutical Policy and Practice     Open Access   (Followers: 4)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 2)
Journal of Physiology-Paris     Hybrid Journal   (Followers: 2)
Journal of Pioneering Medical Sciences     Open Access  
Journal of Postgraduate Medicine     Open Access  
Journal of Pregnancy     Open Access   (Followers: 4)
Journal of Prevention & Intervention Community     Hybrid Journal   (Followers: 7)
Journal of Preventive Medicine and Public Health     Open Access  
Journal of Primary Prevention     Hybrid Journal   (Followers: 7)
Journal of Prosthodontic Research     Full-text available via subscription   (Followers: 1)
Journal of Prosthodontics     Hybrid Journal   (Followers: 2)
Journal of Receptor, Ligand and Channel Research     Open Access   (Followers: 1)
Journal of Regenerative Medicine     Partially Free   (Followers: 4)
Journal of Research in Medical Sciences     Open Access   (Followers: 2)
Journal of Science and Applications : Biomedicine     Open Access   (Followers: 1)
Journal of Science and Technology (Ghana)     Open Access   (Followers: 3)
Journal of Scientific Innovation in Medicine     Open Access  
Journal of Scientific Perspectives     Open Access   (Followers: 1)
Journal of Sensory Studies     Hybrid Journal   (Followers: 4)
Journal of Shaheed Suhrawardy Medical College     Open Access  
Journal of Shoulder and Elbow Arthroplasty     Open Access  
Journal of Sleep Disorders : Treatment & Care     Hybrid Journal   (Followers: 10)
Journal of South American Earth Sciences     Hybrid Journal   (Followers: 5)
Journal of Spinal Cord Medicine     Hybrid Journal   (Followers: 5)
Journal of Spinal Disorders & Techniques     Hybrid Journal   (Followers: 2)
Journal of Sports Medicine and Allied Health Sciences : Official Journal of the Ohio Athletic Trainers Association     Open Access   (Followers: 1)
Journal of Stem Cell Therapy and Transplantation     Open Access   (Followers: 1)
Journal of Stomal Therapy Australia     Full-text available via subscription   (Followers: 1)
Journal of Strength and Conditioning Research     Hybrid Journal   (Followers: 77)
Journal of Substance Use     Hybrid Journal   (Followers: 15)
Journal of Surgical Academia     Open Access   (Followers: 1)
Journal of Surgical and Clinical Research     Open Access  
Journal of Surgical Case Reports     Open Access  
Journal of Surgical Education     Full-text available via subscription   (Followers: 3)
Journal of Surgical Technique and Case Report     Open Access  
Journal of Systemic Therapies     Full-text available via subscription   (Followers: 3)
Journal of Taibah University Medical Sciences     Open Access  
Journal of Telemedicine and Telecare     Hybrid Journal   (Followers: 12)
Journal of The Academy of Clinical Microbiologists     Open Access  
Journal of the American Association for Laboratory Animal Science     Full-text available via subscription   (Followers: 9)
Journal of the American College of Certified Wound Specialists     Hybrid Journal   (Followers: 2)
Journal of the American College of Clinical Wound Specialists     Hybrid Journal   (Followers: 2)
Journal of the American Medical Directors Association     Hybrid Journal   (Followers: 5)
Journal of the American Medical Informatics Association : JAMIA     Hybrid Journal   (Followers: 36)
Journal of the American Podiatric Medical Association     Full-text available via subscription   (Followers: 7)
Journal of the Anatomical Society of India     Full-text available via subscription  
Journal of the Anus, Rectum and Colon     Open Access  
Journal of The Arab Society for Medical Research     Open Access  

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Similar Journals
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Journal of Personalized Medicine
Journal Prestige (SJR): 1.269
Citation Impact (citeScore): 3
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2075-4426
Published by MDPI Homepage  [231 journals]
  • JPM, Vol. 10, Pages 141: Deep Learning for Whole-Slide Tissue
           Histopathology Classification: A Comparative Study in the Identification
           of Dysplastic and Non-Dysplastic Barrett’s Esophagus

    • Authors: Rasoul Sali, Nazanin Moradinasab, Shan Guleria, Lubaina Ehsan, Philip Fernandes, Tilak U. Shah, Sana Syed, Donald E. Brown
      First page: 141
      Abstract: The gold standard of histopathology for the diagnosis of Barrett’s esophagus (BE) is hindered by inter-observer variability among gastrointestinal pathologists. Deep learning-based approaches have shown promising results in the analysis of whole-slide tissue histopathology images (WSIs). We performed a comparative study to elucidate the characteristics and behaviors of different deep learning-based feature representation approaches for the WSI-based diagnosis of diseased esophageal architectures, namely, dysplastic and non-dysplastic BE. The results showed that if appropriate settings are chosen, the unsupervised feature representation approach is capable of extracting more relevant image features from WSIs to classify and locate the precursors of esophageal cancer compared to weakly supervised and fully supervised approaches.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-23
      DOI: 10.3390/jpm10040141
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 142: A Closer Look at the “Right” Format for
           Clinical Decision Support: Methods for Evaluating a Storyboard
           BestPractice Advisory

    • Authors: Brian J. Douthit, R. Clayton Musser, Kay S. Lytle, Rachel L. Richesson
      First page: 142
      Abstract: (1) Background: The five rights of clinical decision support (CDS) are a well-known framework for planning the nuances of CDS, but recent advancements have given us more options to modify the format of the alert. One-size-fits-all assessments fail to capture the nuance of different BestPractice Advisory (BPA) formats. To demonstrate a tailored evaluation methodology, we assessed a BPA after implementation of Storyboard for changes in alert fatigue, behavior influence, and task completion; (2) Methods: Data from 19 weeks before and after implementation were used to evaluate differences in each domain. Individual clinics were evaluated for task completion and compared for changes pre- and post-redesign; (3) Results: The change in format was correlated with an increase in alert fatigue, a decrease in erroneous free text answers, and worsened task completion at a system level. At a local level, however, 14% of clinics had improved task completion; (4) Conclusions: While the change in BPA format was correlated with decreased performance, the changes may have been driven primarily by the COVID-19 pandemic. The framework and metrics proposed can be used in future studies to assess the impact of new CDS formats. Although the changes in this study seemed undesirable in aggregate, some positive changes were observed at the level of individual clinics. Personalized implementations of CDS tools based on local need should be considered.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-23
      DOI: 10.3390/jpm10040142
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 143: “They’re Not Going to Do Nothing for Me”:
           Research Participants’ Attitudes towards Elective Genetic Counseling

    • Authors: Erica J. Sutton, Annika T. Beck, Kylie O. Gamm, Jennifer B. McCormick, Iftikhar J. Kullo, Richard R. Sharp
      First page: 143
      Abstract: As applications of genomic sequencing have expanded, offering genetic counseling support to all patients is arguably no longer practical. Additionally, whether individuals desire and value genetic counseling services for genomic screening is unclear. We offered elective genetic counseling to 5110 individuals prior to undergoing sequencing and 2310 participants who received neutral results to assess demand. A total of 0.2% of the study participants accessed genetic counseling services prior to sequencing, and 0.3% reached out after receiving neutral results. We later conducted 50 interviews with participants to understand why they did not access these services. Many interviewees did not recall the availability of genetic counseling and were unfamiliar with the profession. Interviewees described not needing counseling before sequencing because they understood the study and felt that they could cope with any result. Counseling was considered equally unnecessary after learning neutral results. Although the participants had questions about their results, they did not feel that speaking with a genetic counselor would be helpful. Genomic screening efforts that employ opt-in models of genetic counseling may need to clarify the potential value of genetic counseling support from the outset and feature genetic counseling services more prominently in program materials.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-24
      DOI: 10.3390/jpm10040143
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 144: Reframing Psychiatry for Precision Medicine

    • Authors: Elizabeth B. Torres
      First page: 144
      Abstract: The art of observing and describing behaviors has driven diagnosis and informed basic science in psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In precision medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes gene expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate gene expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing gene expression on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological conditions. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g., autism, schizophrenia, and depression) through DSM-observation criteria have strong convergence with well-known neurological conditions (e.g., ataxias and Parkinson’s disease), but less overlap with non-neurological conditions. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain–body connection and the contributions of the peripheral nervous systems to mental health.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-25
      DOI: 10.3390/jpm10040144
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 145: Pharmaconutrition in the Clinical Management of
           COVID-19: A Lack of Evidence-Based Research But Clues to Personalized

    • Authors: Heitor O. Santos, Grant M. Tinsley, Guilherme A. R. da Silva, Allain A. Bueno
      First page: 145
      Abstract: A scientific interest has emerged to identify pharmaceutical and nutritional strategies in the clinical management of coronavirus disease 2019 (COVID-19). The purpose of this narrative review is to critically assess and discuss pharmaconutrition strategies that, secondary to accepted treatment methods, could be candidates in the current context of COVID-19. Oral medicinal doses of vitamin C (1–3 g/d) and zinc (80 mg/d elemental zinc) could be promising at the first signs and symptoms of COVID-19 as well as for general colds. In critical care situations requiring parenteral nutrition, vitamin C (3–10 g/d) and glutamine (0.3–0.5 g/kg/d) administration could be considered, whereas vitamin D3 administration (100,000 IU administered intramuscularly as a one-time dose) could possess benefits for patients with severe deficiency. Considering the presence of n-3 polyunsaturated fatty acids and arginine in immune-enhancing diets, their co-administration may also occur in clinical conditions where these formulations are recommended. However, despite the use of the aforementioned strategies in prior contexts, there is currently no evidence of the utility of any nutritional strategies in the management of SARS-CoV-2 infection and COVID-19. Nevertheless, ongoing and future clinical research is imperative to determine if any pharmaconutrition strategies can halt the progression of COVID-19.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-25
      DOI: 10.3390/jpm10040145
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 146: Impact of Comorbidities on SARS-CoV-2 Viral
           Entry-Related Genes

    • Authors: Joshua D. Breidenbach, Prabhatchandra Dube, Subhanwita Ghosh, Belal N. Abdullah, Nikolai N. Modyanov, Deepak Malhotra, Lance D. Dworkin, Steven T. Haller, David J. Kennedy
      First page: 146
      Abstract: Viral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. The distribution and expression of many of these genes across cell types representing multiple organ systems in healthy individuals has recently been demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and are associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remains unclear. Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals. Additionally, we found the increased expression of viral entry-related genes in the settings of hypertension, cancer, or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and we suggest new therapeutic targets to improve outcomes in vulnerable patient populations.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-25
      DOI: 10.3390/jpm10040146
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 147: Personalized Medicine for Antibiotics: The Role
           of Nanobiosensors in Therapeutic Drug Monitoring

    • Authors: Vivian Garzón, Rosa-Helena Bustos, Daniel G. Pinacho
      First page: 147
      Abstract: Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-25
      DOI: 10.3390/jpm10040147
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 148: Characterisation of MRI Indeterminate Breast
           Lesions Using Dedicated Breast PET and Prone FDG PET-CT in Patients with
           Breast Cancer—A Proof-of-Concept Study

    • Authors: Anmol Malhotra, Sophia Tincey, Vishnu Naidu, Carla Papagiorcopulo, Debashis Ghosh, Peng H. Tan, Fred Wickham, Thomas Wagner
      First page: 148
      Abstract: Magnetic resonance imaging (MRI) in patients with breast cancer to assess extent of disease or multifocal disease can demonstrate indeterminate lesions requiring second-look ultrasound and ultrasound or MRI-guided biopsies. Prone positron emission tomography-computed tomography (PET-CT) is a dedicated acquisition performed with a breast-supporting device on a standard PET-CT scanner. The MAMmography with Molecular Imaging (MAMMI, Oncovision, Valencia, Spain) PET system (PET-MAMMI) is a true tomographic ring scanner for the breast. We investigated if PET-MAMMI and prone PET-CT were able to characterise these MRI- indeterminate lesions further. A total of 10 patients with breast cancer and indeterminate lesions on breast MRI were included. Patients underwent prone PET-MAMMI and prone PET-CT after injection of FDG subsequently on the same day. Patients then resumed their normal pathway, with the clinicians blinded to the results of the PET-MAMMI and prone PET-CT. Of the MRI-indeterminate lesions, eight were histopathologically proven to be malignant and two were benign. PET-MAMMI and prone PET-CT only were able to demonstrate increased FDG uptake in 1/8 and 0/8 of the MRI-indeterminate malignant lesions, respectively. Of the MRI-indeterminate benign lesions, both PET-MAMMI and prone PET-CT demonstrated avidity in 1/2 of these lesions. Our findings do not support the use of PET-MAMMI to characterise indeterminate breast MRI lesions requiring a second look ultrasound.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-25
      DOI: 10.3390/jpm10040148
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 149: Clinical and Laboratory Associations with
           Methotrexate Metabolism Gene Polymorphisms in Rheumatoid Arthritis

    • Authors: Leon G. D’Cruz, Kevin G. McEleney, Kyle B. C. Tan, Priyank Shukla, Philip V. Gardiner, Patricia Connolly, Caroline Conway, Diego Cobice, David S. Gibson
      First page: 149
      Abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD-metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease collected at two intervals. Taqman probes were used to discriminate single-nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p < 0.05) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles have significantly higher (p < 0.001) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p < 0.05) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit whilst minimizing toxicity.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-26
      DOI: 10.3390/jpm10040149
      Issue No: Vol. 10, No. 4 (2020)
  • JPM, Vol. 10, Pages 55: A Discussion on Different Approaches for
           Prescribing Physical Interventions – Four Roads Lead to Rome, but Which
           One Should We Choose'

    • Authors: Fabian Herold, Alexander Törpel, Dennis Hamacher, Henning Budde, Thomas Gronwald
      First page: 55
      Abstract: It is well recognized that regular physical exercise has positive effects on physical and mental health. To use the beneficial health effects of physical exercise, there are worldwide movements encouraging health care providers to include physical exercise in their care and treatments strategies. However, a crucial point in administering the “exercise polypill” is the dosing and, in turn, the prescription of the physical intervention (PI). In this perspective article, we discuss the advantages and disadvantages of different approaches to prescribe PI. In this context, we also highlight outstanding questions and potential areas of opportunity for further investigations.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-27
      DOI: 10.3390/jpm10030055
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 56: Nursing Personnel in the Era of Personalized
           Healthcare in Clinical Practice

    • Authors: Marios Spanakis, Athina E. Patelarou, Evridiki Patelarou
      First page: 56
      Abstract: Personalized, stratified, or precision medicine (PM) introduces a new era in healthcare that tries to identify and predict optimum treatment outcomes for a patient or a cohort. It also introduces new scientific terminologies regarding therapeutic approaches and the need of their adoption from healthcare providers. Till today, evidence-based practice (EBP) was focusing on population averages and their variances among cohorts for clinical values that are essential for optimizing healthcare outcome. It can be stated that EBP and PM are complementary approaches for a modern healthcare system. Healthcare providers through EBP often see the forest (population averages) but miss the trees (individual patients), whereas utilization of PM may not see the forest for the trees. Nursing personnel (NP) play an important role in modern healthcare since they are consulting, educating, and providing care to patients whose needs often needs to be individualized (personalized nursing care, PNC). Based on the clinical issues earlier addressed from clinical pharmacology, EBP, and now encompassed in PM, this review tries to describe the challenges that NP have to face in order to meet the requisites of the new era in healthcare. It presents the demands that should be met for upgrading the provided education and expertise of NP toward an updated role in a modern healthcare system.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-29
      DOI: 10.3390/jpm10030056
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 57: Semantic Priming in Mild Cognitive Impairment and
           Healthy Subjects: Effect of Different Time of Presentation of Word-Pairs

    • Authors: Valeria Guglielmi, Davide Quaranta, Ilaria Mega, Emanuele Maria Costantini, Claudia Carrarini, Alice Innocenti, Camillo Marra
      First page: 57
      Abstract: Introduction: Semantic memory is impaired in mild cognitive impairment (MCI). Twomain hypotheses about this finding are debated and refer to the degradation of stored knowledgeversus the impairment of semantic access mechanisms. The aim of our study is to evaluate semanticimpairment in MCI versus healthy subjects (HS) by an experiment evaluating semantic priming.Methods: We enrolled 27 MCI and 20 HS. MCI group were divided, according to follow up, intoconverters-MCI and non converters-MCI. The semantic task consisted of 108 pairs of words, 54 ofwhich were semantically associated. Stimuli were presented 250 or 900 ms later the appearance ofthe target in a randomized manner. Data were analyzed using factorial ANOVA. Results: Both HSand MCI answered more quickly for word than for non-word at both stimulus onset asynchrony(SOA) intervals. At 250 ms, both MCI and HS experienced a shorter time of response for relatedwordthan for unrelated words (priming effect), while only the converters-MCI subgroup lost thepriming effect. Further, we observed a rather larger Cohen’s d effect size in non converters-MCIthan in converters-MCI. Conclusion: Our data, and in particular the absence of a semantic primingeffect in converters-MCI, could reflect the impairment of semantic knowledge rather than theaccessibility of semantic stores in MCI individuals that progress to dementia.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-29
      DOI: 10.3390/jpm10030057
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 58: A Systematic Review of Genotype–Phenotype
           Correlation across Cohorts Having Causal Mutations of Different Genes in

    • Authors: Owen Connolly, Laura Le Le Gall, Gavin McCluskey, Colette G Donaghy, William J Duddy, Stephanie Duguez
      First page: 58
      Abstract: Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-29
      DOI: 10.3390/jpm10030058
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 59: Stereotactic Radiotherapy for Brain Metastases:
           Imaging Tools and Dosimetric Predictive Factors for Radionecrosis

    • Authors: Marco Lupattelli, Emanuele Alì, Gianluca Ingrosso, Simonetta Saldi, Christian Fulcheri, Simona Borghesi, Roberto Tarducci, Cynthia Aristei
      First page: 59
      Abstract: Radionecrosis (RN) is the most important side effect after stereotactic radiotherapy (SRT) for brain metastases, with a reported incidence ranging from 3% to 24%. To date, there are no unanimously accepted criteria for iconographic diagnosis of RN, as well as no definitive dose-constraints correlated with the onset of this late effect. We reviewed the current literature and gave an overview report on imaging options for the diagnosis of RN and on dosimetric parameters correlated with the onset of RN. We performed a PubMed literature search according to the preferred reporting items and meta-analysis (PRISMA) guidelines, and identified articles published within the last ten years, up to 31 December 2019. When analyzing data on diagnostic tools, perfusion magnetic resonance imaging (MRI) seems to be very useful allowing evaluation of the blood flow in the lesion using the relative cerebral blood volume (rCBV) and blood vessel integrity using relative peak weight (rPH). It is necessary to combine morphological with functional imaging in order to match information about lesion morphology, metabolism and blood-flow. Eventually, serial imaging follow-up is needed. Regarding dosimetric parameters, in radiosurgery (SRS) V12 < 8 cm3 and V10 < 10.5 cm3 of normal brain are the most reliable prognostic factors, whereas in hypo-fractionated stereotactic radiotherapy (HSRT) V18 and V21 are considered the main predictive independent risk factors of RN.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-04
      DOI: 10.3390/jpm10030059
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 60: Possible Differential Diagnosis of the Degrees of
           Rheological Disturbances in Patients with Type 2 Diabetes Mellitus by
           Dielectrophoresis of Erythrocytes

    • Authors: Margarita V. Kruchinina, Andrey A. Gromov, Vladimir M. Generalov, Vladimir N. Kruchinin
      First page: 60
      Abstract: Hemorheological disorders in structural and functional parameters of erythrocytes are involved in the pathological process in type 2 diabetes mellitus (DM). Aim: to investigate the feasibility of differential diagnosis of the degrees of rheological disturbances in patients with type 2 DM by dielectrophoresis of erythrocytes. Methods: 62 subjects (58.7 ± 1.6 years) with type 2 DM diagnosed according to the criteria of the ADA were subdivided into two groups: medium (n = 47) and high (n = 15) risk of microcirculatory disturbances (EASD, 2013). Electric and viscoelastic parameters of erythrocytes were determined by dielectrophoresis using an electric optical system of cell detection. Results: the progression of rheological disturbances in the patients with type 2 DM was accompanied by significant decreases in deformation amplitude; dipole moment; polarizability; and membrane capacity; and increases in conductivity, viscosity, rigidity, hemolysis, and formation of aggregates (p < 0.05). Combined use of the parameters increased sensitivity (97.8%) and specificity (86.7%) for diagnosis of rheological disturbances in type 2 DM. Conclusion: the proposed experimental approach possesses low invasiveness, high productivity, shorter duration, vividness of the results. The method allows to evaluate not only local (renal and ocular) but also systemic status of microcirculation using more than 20 parameters of erythrocytes.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-05
      DOI: 10.3390/jpm10030060
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 61: Molecular and Imaging Biomarkers in Alzheimer’s
           Disease: A Focus on Recent Insights

    • Authors: Chiara Villa, Marialuisa Lavitrano, Elena Salvatore, Romina Combi
      First page: 61
      Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly, affecting millions of people worldwide and clinically characterized by a progressive and irreversible cognitive decline. The rapid increase in the incidence of AD highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods rely on measures of amyloid-β (Aβ), phosphorylated (p-tau) and total tau (t-tau) protein levels in the cerebrospinal fluid (CSF) aided by advanced neuroimaging techniques like positron emission tomography (PET) and magnetic resonance imaging (MRI). However, the invasiveness of these procedures and the high cost restrict their utilization. Hence, biomarkers from biological fluids obtained using non-invasive methods and novel neuroimaging approaches provide an attractive alternative for the early diagnosis of AD. Such biomarkers may also be helpful for better understanding of the molecular mechanisms underlying the disease, allowing differential diagnosis or at least prolonging the pre-symptomatic stage in patients suffering from AD. Herein, we discuss the advantages and limits of the conventional biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-10
      DOI: 10.3390/jpm10030061
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 62: Automatic Labeled Dialogue Generation for Nursing
           Record Systems

    • Authors: Tittaya Mairittha, Nattaya Mairittha, Sozo Inoue
      First page: 62
      Abstract: The integration of digital voice assistants in nursing residences is becoming increasingly important to facilitate nursing productivity with documentation. A key idea behind this system is training natural language understanding (NLU) modules that enable the machine to classify the purpose of the user utterance (intent) and extract pieces of valuable information present in the utterance (entity). One of the main obstacles when creating robust NLU is the lack of sufficient labeled data, which generally relies on human labeling. This process is cost-intensive and time-consuming, particularly in the high-level nursing care domain, which requires abstract knowledge. In this paper, we propose an automatic dialogue labeling framework of NLU tasks, specifically for nursing record systems. First, we apply data augmentation techniques to create a collection of variant sample utterances. The individual evaluation result strongly shows a stratification rate, with regard to both fluency and accuracy in utterances. We also investigate the possibility of applying deep generative models for our augmented dataset. The preliminary character-based model based on long short-term memory (LSTM) obtains an accuracy of 90% and generates various reasonable texts with BLEU scores of 0.76. Secondly, we introduce an idea for intent and entity labeling by using feature embeddings and semantic similarity-based clustering. We also empirically evaluate different embedding methods for learning good representations that are most suitable to use with our data and clustering tasks. Experimental results show that fastText embeddings produce strong performances both for intent labeling and on entity labeling, which achieves an accuracy level of 0.79 and 0.78 f1-scores and 0.67 and 0.61 silhouette scores, respectively.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-16
      DOI: 10.3390/jpm10030062
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 63: Advantages and Pitfalls in Fluid Biomarkers for
           Diagnosis of Alzheimer’s Disease

    • Authors: Syed Haris Omar, John Preddy
      First page: 63
      Abstract: Alzheimer’s disease (AD) is a commonly occurring neurodegenerative disease in the advanced-age population, with a doubling of prevalence for each 5 years of age above 60 years. In the past two decades, there has been a sustained effort to find suitable biomarkers that may not only aide with the diagnosis of AD early in the disease process but also predict the onset of the disease in asymptomatic individuals. Current diagnostic evidence is supportive of some biomarker candidates isolated from cerebrospinal fluid (CSF), including amyloid beta peptide (Aβ), total tau (t-tau), and phosphorylated tau (p-tau) as being involved in the pathophysiology of AD. However, there are a few biomarkers that have been shown to be helpful, such as proteomic, inflammatory, oral, ocular and olfactory in the early detection of AD, especially in the individuals with mild cognitive impairment (MCI). To date, biomarkers are collected through invasive techniques, especially CSF from lumbar puncture; however, non-invasive (radio imaging) methods are used in practice to diagnose AD. In order to reduce invasive testing on the patients, present literature has highlighted the potential importance of biomarkers in blood to assist with diagnosing AD.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-17
      DOI: 10.3390/jpm10030063
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 64: Patient-Derived Tumor Xenograft Models: Toward the
           Establishment of Precision Cancer Medicine

    • Authors: Goto
      First page: 64
      Abstract: Patient-derived xenografts (PDXs) describe models involving the implantation of patient-derived tumor tissue into immunodeficient mice. Compared with conventional preclinical models involving the implantation of cancer cell lines into mice, PDXs can be characterized by the preservation of tumor heterogeneity, and the tumor microenvironment (including stroma/vasculature) more closely resembles that in patients. Consequently, the use of PDX models has improved the predictability of clinical therapeutic responses to 80% or greater, compared with approximately 5% for existing models. In the future, molecular biological analyses, omics analyses, and other experiments will be conducted using recently prepared PDX models under the strong expectation that the analysis of cancer pathophysiology, stem cells, and novel treatment targets and biomarkers will be improved, thereby promoting drug development. This review outlines the methods for preparing PDX models, advances in cancer research using PDX mice, and perspectives for the establishment of precision cancer medicine within the framework of personalized cancer medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-18
      DOI: 10.3390/jpm10030064
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 65: A Web-Based Pharmacogenomics Search Tool for
           Precision Medicine in Perioperative Care

    • Authors: Sara Zarei, Yensea Costas, Gloria Orozco, Michelle Zaydlin, Ali Mirtar, Mohammad Abouali, Cristina Diaz-Marty, Golnoush Akhlaghipour, Pablo Fernandez Altamirano, Anel R. Gonzalez Cardona, Luz E. Reiley, Hooman Mirzakhani
      First page: 65
      Abstract: Background: Precision medicine represents an evolving approach to improve treatment efficacy by modifying it to individual patient’s gene variation. Pharmacogenetics, an applicable branch of precision medicine, identifies patient’s predisposing genotypes that alter the clinical outcome of the drug, hence preventing serious adverse drug reactions. Pharmacogenetics has been extensively applied to various fields of medicine, but in the field of anesthesiology and preoperative medicine, it has been unexploited. Although the US Food and Drug Administration (FDA) has a table of pharmacogenomics biomarkers and pharmacogenetics, this table only includes general side effects of the included drugs. Thus, the existing FDA table offers limited information on genetic variations that may increase drug side effects. Aims: The purpose of this paper is to provide a web-based pharmacogenomics search tool composed of a comprehensive list of medications that have pharmacogenetic relevance to perioperative medicine that might also have application in other fields of medicine. Method: For this investigation, the FDA table of pharmacogenomics biomarkers in drug labeling was utilized as an in-depth of drugs to construct our pharmacogenetics drug table. We performed a literature search for drug–gene interactions using the unique list of drugs in the FDA table. Publications containing the drug–gene interactions were identified and reviewed. Additional drugs and extracted gene-interactions in the identified publications were added to the constructed drug table. Result: Our tool provides a comprehensive pharmacogenetic drug table including 258 drugs with a total of 461 drug–gene interactions and their corresponding gene variations that might cause modifications in drug efficacy, pharmacokinetics, pharmacodynamics and adverse reactions. This tool is freely accessible online and can be applied as a web-based search instrument for drug–gene interactions in different fields of medicine, including perioperative medicine. Conclusion: In this research, we collected drug–gene interactions in a web-based searchable tool that could be used by physicians to expand their field knowledge in pharmacogenetics and facilitate their clinical decision making. This precision medicine tool could further serve in establishing a comprehensive perioperative pharmacogenomics database that also includes different fields of medicine that could influence the outcome of perioperative medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-21
      DOI: 10.3390/jpm10030065
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 66: Adipose-Derived Stem Cells Reduce
           Lipopolysaccharide-Induced Myelin Degradation and Neuroinflammatory
           Responses of Glial Cells in Mice

    • Authors: Kateryna Yatsenko, Iryna Lushnikova, Alina Ustymenko, Maryna Patseva, Iryna Govbakh, Vitalii Kyryk, Oleg Tsupykov
      First page: 66
      Abstract: Brain inflammation is a key event triggering the pathological process associated with many neurodegenerative diseases. Current personalized medicine and translational research in neurodegenerative diseases focus on adipose-derived stem cells (ASCs), because they are patient-specific, thereby reducing the risk of immune rejection. ASCs have been shown to exert a therapeutic effect following transplantation in animal models of neuroinflammation. However, the mechanisms by which transplanted ASCs promote cell survival and/or functional recovery are not fully understood. We investigated the effects of ASCs in in vivo and in vitro lipopolysaccharide (LPS)-induced neuroinflammatory models. Brain damage was evaluated immunohistochemically using specific antibody markers of microglia, astroglia and oligodendrocytes. ASCs were used for intracerebral transplantation, as well as for non-contact co-culture with brain slices. In both in vivo and in vitro models, we found that LPS caused micro- and astroglial activation and oligodendrocyte degradation, whereas the presence of ASCs significantly reduced the damaging effects. It should be noted that the observed ASCs protection in a non-contact co-culture suggested that this effect was due to humoral factors via ASC-released biomodulatory molecules. However, further clinical studies are required to establish the therapeutic mechanisms of ASCs, and optimize their use as a part of a personalized medicine strategy.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-22
      DOI: 10.3390/jpm10030066
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 67: An Implementation Science Framework to Develop a
           Clinical Decision Support Tool for Familial Hypercholesterolemia

    • Authors: Hana Bangash, Laurie Pencille, Justin H. Gundelach, Ahmed Makkawy, Joseph Sutton, Lenae Makkawy, Ozan Dikilitas, Stephen Kopecky, Robert Freimuth, Pedro J. Caraballo, Iftikhar J. Kullo
      First page: 67
      Abstract: Electronic health record (EHR)-based clinical decision support (CDS) can address the low awareness and undertreatment of familial hypercholesterolemia (FH), a disorder associated with a markedly increased risk of coronary heart disease. We aimed to incorporate provider perspectives into the development and implementation of a CDS tool for FH. An implementation science framework and a user-centered design process were used to create a CDS tool for FH. Primary care physicians and specialist physicians participated in qualitative interviews, usability testing and an implementation survey. The CDS was configured in two formats—a best practice alert (BPA) and an in-basket message and subsequently deployed in the EHR in silent mode. The key themes that emerged from the analysis of interview transcripts included understanding and awareness of FH, clinical workflow, physician preferences and value of CDS tools, perspectives on patient needs and values and dissemination and implementation. Recommendations related to usability included preferred CDS format and placement, content, timing and frequency, and level of alert urgency/prioritization. In response to the survey, 84.6% of physicians agreed that the CDS would improve early FH diagnosis and 92.3% agreed that it would help them identify and manage FH patients. Physician feedback led to iterative CDS refinement. In summary, we developed a CDS tool for FH using an implementation science framework and physician feedback. Initial deployment revealed a significant burden of FH and the potential for the CDS tool to have a large impact.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-23
      DOI: 10.3390/jpm10030067
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 68: Use of Biomarkers in Ongoing Research Protocols on
           Alzheimer’s Disease

    • Authors: Marco Canevelli, Giulia Remoli, Ilaria Bacigalupo, Martina Valletta, Marco Toccaceli Blasi, Francesco Sciancalepore, Giuseppe Bruno, Matteo Cesari, Nicola Vanacore
      First page: 68
      Abstract: The present study aimed to describe and discuss the state of the art of biomarker use in ongoing Alzheimer’s disease (AD) research. A review of 222 ongoing phase 1, 2, 3, and 4 protocols registered in the database was performed. All the trials (i) enrolling subjects with clinical disturbances and/or preclinical diagnoses falling within the AD continuum; and (ii) testing the efficacy and/or safety/tolerability of a therapeutic intervention, were analyzed. The use of biomarkers of amyloid deposition, tau pathology, and neurodegeneration among the eligibility criteria and/or study outcomes was assessed. Overall, 58.2% of ongoing interventional studies on AD adopt candidate biomarkers. They are mostly adopted by studies at the preliminary stages of the drug development process to explore the safety profile of novel therapies, and to provide evidence of target engagement and disease-modifying properties. The biologically supported selection of participants is mostly based on biomarkers of amyloid deposition, whereas the use of biomarkers as study outcomes mostly relies on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. Nevertheless, their clinical validity, utility, and cost-effectiveness in the “real world” remain to be clarified.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-24
      DOI: 10.3390/jpm10030068
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 69: Relationship between Blood and Standard
           Biochemistry Levels with Periodontitis in Parkinson’s Disease Patients:
           Data from the NHANES 2011–2012

    • Authors: João Botelho, Patrícia Lyra, Luís Proença, Catarina Godinho, José João Mendes, Vanessa Machado
      First page: 69
      Abstract: People with Parkinson’s Disease (PD) are associated with the presence of periodontitis. We aimed to compare blood and standard biochemical surrogates of PD patients diagnosed with periodontitis with PD individuals without periodontitis. This retrospective cohort study used a sample from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 that underwent periodontal diagnosis (n = 3669). PD participants were identified through specific PD reported medications. Periodontitis was defined according to the 2012 case definition, using periodontal examination data provided. Then, we compared blood levels and standard chemical laboratory profiles of PD patients according to the presence of periodontitis. Multivariable regression was used to explore this dataset and identify relevant variables towards the presence of periodontitis. According to the medication report, 37 participants were eligible, 29 were secure and 8 were unsecure PD medications regimens. Overall, PD cases with periodontitis presented increased levels of White Blood Cells (WBC) (p = 0.002), Basophils (p = 0.045) and Segmented neutrophils (p = 0.009), and also, lower levels of Total Bilirubin (p = 0.018). In the PD secure medication group, a significant difference was found for WBC (p = 0.002) and Segmented neutrophils (p = 0.002) for the periodontitis group. Further, WBC might be a discriminating factor towards periodontitis in the global sample. In the secure PD medication, we found gender, segmented neutrophils and Vitamin D2 to be potential discriminative variables towards periodontitis. Thus, periodontitis showed association with leukocyte levels alterations in PD patients, and therefore with potential systemic changes and predictive value. Furthermore, Vitamin D2 and gender showed to be associated with periodontitis in with secure medication for PD. Future studies should assess in more detail the potential systemic repercussion of the presence of periodontitis in PD patients.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-25
      DOI: 10.3390/jpm10030069
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 70: Correlations between Iron Metabolism Parameters,
           Inflammatory Markers and Lipid Profile Indicators in Patients with Type 1
           and Type 2 Diabetes Mellitus

    • Authors: Nadezhda N. Musina, Tatiana V. Saprina, Tatiana S. Prokhorenko, Alexander Kanev, Anastasia P. Zima
      First page: 70
      Abstract: This study aims to establish relationships between inflammatory status, ferrokinetics and lipid metabolism in patients with diabetes mellitus. Subclinical inflammation was assessed by levels of high-sensitive C-reactive protein, tumor necrosis factor-α and erythrocyte sedimentation rate. Iron metabolism parameters included complete blood count, serum iron, transferrin and ferritin. Metabolic status assessment included lipid profile, glycated hemoglobin and microalbuminuria measurement. As a result of the study it was possible to establish both general (universal) and diabetes mellitus (DM) type-dependent relationships between the parameters of lipid profile and metabolic control in DM. High-density lipoprotein cholesterol (HDL-C) levels negatively correlated with microalbuminuria (r = −0.293; p ˂ 0.05 for type 1 diabetes and r = −0.272; p ˂ 0.05 for type 2 diabetes). Ferritin concentration positively correlated with triglyceride level (r = 0.346; p ˂ 0.05 for type 1 diabetes and r = 0.244; p ˂ 0.05 for type 2 diabetes). In type 1 diabetes, a negative correlation was discovered between estimated glomerular filtration rate (eGFR) and LDL-C (r = −0.480; p ˂ 0.05), very low-density-lipoprotein cholesterol (VLDL-C) (r = −0.490; p ˂ 0.05) and triglycerides (r = −0.553; p ˂ 0.05), and a positive one between C-reactive protein concentration and triglyceride level (r = 0.567; p ˂ 0.05). Discovered relationships between lipid profile indices, inflammatory status and microalbuminuria confirmed mutual influence of hyperlipidemia, inflammation and nephropathy in diabetes patients. Obtained results justify the strategy of early hypolipidemic therapy in patients with diabetes mellitus to prevent the development and progression of microvascular complications.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-25
      DOI: 10.3390/jpm10030070
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 71: Relative Biological Effectiveness of Carbon Ions
           for Head-and-Neck Squamous Cell Carcinomas According to Human
           Papillomavirus Status

    • Authors: Naoto Osu, Daijiro Kobayashi, Katsuyuki Shirai, Atsushi Musha, Hiro Sato, Yuka Hirota, Atsushi Shibata, Takahiro Oike, Tatsuya Ohno
      First page: 71
      Abstract: Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-25
      DOI: 10.3390/jpm10030071
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 72: Markers Useful in Monitoring Radiation-Induced
           Lung Injury in Lung Cancer Patients: A Review

    • Authors: Mariola Śliwińska-Mossoń, Katarzyna Wadowska, Łukasz Trembecki, Iwona Bil-Lula
      First page: 72
      Abstract: In 2018, lung cancer was the most common cancer and the most common cause of cancer death, accounting for a 1.76 million deaths. Radiotherapy (RT) is a widely used and effective non-surgical cancer treatment that induces remission in, and even cures, patients with lung cancer. However, RT faces some restrictions linked to the radioresistance and treatment toxicity, manifesting in radiation-induced lung injury (RILI). About 30–40% of lung cancer patients will develop RILI, which next to the local recurrence and distant metastasis is a substantial challenge to the successful management of lung cancer treatment. These data indicate an urgent need of looking for novel, precise biomarkers of individual response and risk of side effects in the course of RT. The aim of this review was to summarize both preclinical and clinical approaches in RILI monitoring that could be brought into clinical practice. Next to transforming growth factor-β1 (TGFβ1) that was reported as one of the most important growth factors expressed in the tissues after ionizing radiation (IR), there is a group of novel, potential biomarkers—microRNAs—that may be used as predictive biomarkers in therapy response and disease prognosis.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-26
      DOI: 10.3390/jpm10030072
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 73: DUX4 Expression in FSHD Muscles: Focus on Its mRNA

    • Authors: Sidlauskaite, Le Gall, Mariot, Dumonceaux
      First page: 73
      Abstract: Facioscapulohumeral dystrophy (FSHD) is the most frequent muscular disease in adults. FSHD is characterized by a weakness and atrophy of a specific set of muscles located in the face, the shoulder, and the upper arms. FSHD patients may present different genetic defects, but they all present epigenetic alterations of the D4Z4 array located on the subtelomeric part of chromosome 4, leading to chromatin relaxation and, ultimately, to the aberrant expression of one gene called DUX4. Once expressed, DUX4 triggers a cascade of deleterious events, eventually leading to muscle dysfunction and cell death. Here, we review studies on DUX4 expression in skeletal muscle to determine the genetic/epigenetic factors and regulatory proteins governing DUX4 expression, with particular attention to the different transcripts and their very low expression in muscle.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-28
      DOI: 10.3390/jpm10030073
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 74: The Viral Hypothesis in Alzheimer’s Disease:
           Novel Insights and Pathogen-Based Biomarkers

    • Authors: Sean X Naughton, Urdhva Raval, Giulio M. Pasinetti
      First page: 74
      Abstract: Early diagnosis of Alzheimer’s disease (AD) and the identification of significant risk factors are necessary to better understand disease progression, and to develop intervention-based therapies prior to significant neurodegeneration. There is thus a critical need to establish biomarkers which can predict the risk of developing AD before the onset of cognitive decline. A number of studies have indicated that exposure to various microbial pathogens can accelerate AD pathology. Additionally, several studies have indicated that amyloid-β possess antimicrobial properties and may act in response to infection as a part of the innate immune system. These findings have led some to speculate that certain types of infections may play a significant role in AD pathogenesis. In this review, we will provide an overview of studies which suggest pathogen involvement in AD. Additionally, we will discuss a number of pathogen-associated biomarkers which may be effective in establishing AD risk. Infections that increase the risk of AD represent a modifiable risk factor which can be treated with therapeutic intervention. Pathogen-based biomarkers may thus be a valuable tool for evaluating and decreasing AD risk across the population.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-29
      DOI: 10.3390/jpm10030074
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 75: The Identification of Novel Biomarkers Is Required
           to Improve Adult SMA Patient Stratification, Diagnosis and Treatment

    • Authors: Piera Smeriglio, Paul Langard, Giorgia Querin, Maria Grazia Biferi
      First page: 75
      Abstract: Spinal muscular atrophy (SMA) is currently classified into five different subtypes, from the most severe (type 0) to the mildest (type 4) depending on age at onset, best motor function achieved, and copy number of the SMN2 gene. The two recent approved treatments for SMA patients revolutionized their life quality and perspectives. However, upon treatment with Nusinersen, the most widely administered therapy up to date, a high degree of variability in therapeutic response was observed in adult SMA patients. These data, together with the lack of natural history information and the wide spectrum of disease phenotypes, suggest that further efforts are needed to develop precision medicine approaches for all SMA patients. Here, we compile the current methods for functional evaluation of adult SMA patients treated with Nusinersen. We also present an overview of the known molecular changes underpinning disease heterogeneity. We finally highlight the need for novel techniques, i.e., -omics approaches, to capture phenotypic differences and to understand the biological signature in order to revise the disease classification and device personalized treatments.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-29
      DOI: 10.3390/jpm10030075
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 76: The Autonomic Nervous System Differentiates
           between Levels of Motor Intent and End Effector

    • Authors: Jihye Ryu, Elizabeth Torres
      First page: 76
      Abstract: While attempting to bridge motor control and cognitive science, the nascent field of embodied cognition has primarily addressed intended, goal-oriented actions. Less explored, however, have been unintended motions. Such movements tend to occur largely beneath awareness, while contributing to the spontaneous control of redundant degrees of freedom across the body in motion. We posit that the consequences of such unintended actions implicitly contribute to our autonomous sense of action ownership and agency. We question whether biorhythmic activities from these motions are separable from those which intentionally occur. Here we find that fluctuations in the biorhythmic activities of the nervous systems can unambiguously differentiate across levels of intent. More important yet, this differentiation is remarkable when we examine the fluctuations in biorhythmic activity from the autonomic nervous systems. We find that when the action is intended, the heart signal leads the body kinematics signals; but when the action segment spontaneously occurs without instructions, the heart signal lags the bodily kinematics signals. We conclude that the autonomic nervous system can differentiate levels of intent. Our results are discussed while considering their potential translational value.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-31
      DOI: 10.3390/jpm10030076
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 77: The Risk of Osteoporotic Forearm Fractures in
           Postmenopausal Women in a Siberian Population Sample

    • Authors: Elena Mazurenko, Oksana Rymar, Liliya Shcherbakova, Ekaterina Mazdorova, Sofia Malyutina
      First page: 77
      Abstract: The reduction in bone and muscle mass increases in menopausal women and poses a threat to the loss of self-dependence in the elderly. The aim of the study was to assess the frequency of osteoporotic forearm fractures (OFF) in postmenopausal women and to study their association with risk factors for chronic non-communicable diseases (NCD). The study was based on the Russian arm of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) project (Novosibirsk). In a subsample of postmenopausal women aged 55–84 years old (n = 2005), we assessed the history of OFF during the last 3 years and risk factors for fracture and common NCD/. Cross-sectional associations between OFF history and potential determinants were analyzed using multivariable-adjusted logistic regression. A history of OFF in the last 3 years was found in 3.9% women. In a multivariable-adjusted model, the risk of OFF was directly associated with smoking in the past (OR = 2.23; 95% Cl 1.10–4.55), total cholesterol level higher than 200 mg/dL (OR = 1.98; 95% Cl 1.19–3.29), and it was inversely associated with body mass index (OR = 0.91; 95% Cl 0.86–0.96). In studied population sample of postmenopausal women the cross-sectional determinants of osteoporotic forearm fractures were smoking in the past and high total cholesterol value; body mass index protectively related to the risk of osteoporotic fractures. These findings might have implications for fracture prevention in postmenopausal women.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-31
      DOI: 10.3390/jpm10030077
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 78: Drug Use among Nursing Home Residents in Denmark
           for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential
           for Preemptive PGx Testing

    • Authors: Vermehren, Søgaard Nielsen, Jørgensen, Drastrup, Westergaard
      First page: 78
      Abstract: Background: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug–drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. Methods: Drug use among nursing home residents during 2017–2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug–drug interactions were scored in severity by using drug interaction checkers. Results: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. Conclusion: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug–gene but also drug–drug–gene interactions as a supplement to medication review.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-07-31
      DOI: 10.3390/jpm10030078
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 79: Pharmacogenomics, Pharmacokinetics and Circulating
           Proteins as Biomarkers for Bevacizumab Treatment Optimization in Patients
           with Cancer: A Review

    • Authors: Papachristos, Sivolapenko
      First page: 79
      Abstract: Bevacizumab is a monoclonal antibody that targets VEGF-A and inhibits tumor angiogenesis. Bevacizumab is approved for the treatment of various cancer, including metastatic colorectal cancer (mCRC), ovarian cancer, lung cancer, and others. Thus, it is widely used in oncology, but contrary to other therapeutic classes, there is still a lack of validating predictive factors for treatment outcomes with these agents. In recent years, the research for factors predictive of anti-VEGF treatments and especially bevacizumab response has been one of the most competitive translational research fields. Herein, we review and present the available literature of the clinical use of biomarkers, pharmacogenomics (PG), and therapeutic drug monitoring (TDM) approaches that can be used for the optimization of bevacizumab use in the era of precision medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-04
      DOI: 10.3390/jpm10030079
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 80: Postulated Adjuvant Therapeutic Strategies for

    • Authors: Anderson O. Ferreira, Hudson C. Polonini, Eli C. F. Dijkers
      First page: 80
      Abstract: The number of COVID-19 patients is still growing exponentially worldwide due to the high transmissibility of the SARS-CoV-2 virus. Therapeutic agents currently under investigation are antiviral drugs, vaccines, and other adjuvants that could relieve symptoms or improve the healing process. In this review, twelve therapeutic agents that could play a role in prophylaxis or improvement of the COVID-19-associated symptoms (as add-on substances) are discussed. Agents were identified based on their known pharmacologic mechanism of action in viral and/or nonviral fields and are postulated to interact with one or more of the seven known mechanisms associated with the SARS-CoV-2 virus: (i) regulation of the immune system; (ii) virus entrance in the cell; (iii) virus replication; (iv) hyperinflammation; (v) oxidative stress; (vi) thrombosis; and (vii) endotheliitis. Selected agents were immune transfer factor (oligo- and polypeptides from porcine spleen, ultrafiltered at <10 kDa; Imuno TF®), anti-inflammatory natural blend (Uncaria tomentosa, Endopleura uchi and Haematoccocus pluvialis; Miodesin®), zinc, selenium, ascorbic acid, cholecalciferol, ferulic acid, spirulina, N-acetylcysteine, glucosamine sulfate potassium hydrochloride, trans-resveratrol, and maltodextrin-stabilized orthosilicic acid (SiliciuMax®). This review gives the scientific background on the hypothesis that these therapeutic agents can act in synergy in the prevention and improvement of COVID-19-associated symptoms.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-05
      DOI: 10.3390/jpm10030080
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 81: Application of Machine Learning Techniques to
           Analyze Patient Returns to the Emergency Department

    • Authors: Sarasa Cabezuelo
      First page: 81
      Abstract: The study of the quality of hospital emergency services is based on analyzing a set of indicators such as the average time of first medical attention, the average time spent in the emergency department, degree of completion of the medical report and others. In this paper, an analysis is presented of one of the quality indicators: the rate of return of patients to the emergency service less than 72 h from their discharge. The objective of the analysis was to know the variables that influence the rate of return and which prediction model is the best. In order to do this, the data of the activity of the emergency service of a hospital of a reference population of 290,000 inhabitants were analyzed, and prediction models were created for the binary objective variable (rate of return to emergencies) using the logistic regression techniques, neural networks, random forest, gradient boosting and assembly models. Each of the models was analyzed and the result shows that the best model is achieved through a neural network with activation function tanh, algorithm levmar and three nodes in the hidden layer. This model obtains the lowest mean squared error (MSE) and the best area under the curve (AUC) with respect to the rest of the models used.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-07
      DOI: 10.3390/jpm10030081
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 82: Using Machine Learning to Predict 30-Day Hospital
           Readmissions in Patients with Atrial Fibrillation Undergoing Catheter

    • Authors: Man Hung, Evelyn Lauren, Eric Hon, Julie Xu, Bianca Ruiz-Negrón, Megan Rosales, Wei Li, Tanner Barton, Jacob O’Brien, Weicong Su
      First page: 82
      Abstract: Atrial fibrillation (AF) cases are expected to increase over the next several decades, due to the rise in the elderly population. One promising treatment option for AF is catheter ablation, which is increasing in use. We investigated the hospital readmissions data for AF patients undergoing catheter ablation, and used machine learning models to explore the risk factors behind these readmissions. We analyzed data from the 2013 Nationwide Readmissions Database on cases with AF, and determined the relative importance of factors in predicting 30-day readmissions for AF with catheter ablation. Various machine learning methods, such as k-nearest neighbors, decision tree, and support vector machine were utilized to develop predictive models with their accuracy, precision, sensitivity, specificity, and area under the curve computed and compared. We found that the most important variables in predicting 30-day hospital readmissions in patients with AF undergoing catheter ablation were the age of the patient, the total number of discharges from a hospital, and the number of diagnoses on the patient’s record, among others. Out of the methods used, k-nearest neighbor had the highest prediction accuracy of 85%, closely followed by decision tree, while support vector machine was less desirable for these data. Hospital readmissions for AF with catheter ablation can be predicted with relatively high accuracy, utilizing machine learning methods. As patient age, the total number of hospital discharges, and the total number of patient diagnoses increase, the risk of hospital readmissions increases.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-09
      DOI: 10.3390/jpm10030082
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 83: Protein Expression Analysis of an In Vitro Murine
           Model of Prostate Cancer Progression: Towards Identification of
           High-Potential Therapeutic Targets

    • Authors: Hisham F. Bahmad, Wenjing Peng, Rui Zhu, Farah Ballout, Alissar Monzer, Mohamad K. Elajami, Firas Kobeissy, Wassim Abou-Kheir, Yehia Mechref
      First page: 83
      Abstract: Background: Prostate cancer (PC) is the most frequently diagnosed cancer among men worldwide. The poor prognosis of PC is largely due to late diagnosis of the disease when it has progressed to advanced stages marked by androgen-independence. We interrogated proteomic signatures that embody the transition of PC from an androgen-dependent (AD) to an androgen-independent (AI) state. Methods: We have previously established AD and AI murine PC cell lines, PLum-AD and PLum-AI, respectively, which recapitulate primary and progressive PC at phenotypic and subcellular levels. We statistically surveyed global protein expression profiles in these cell lines. Differential profiles were functionally interrogated by pathways and protein–protein interaction network analyses. Results: Protein expression pattern analysis revealed a total of 683 proteins, among which 99 were significantly differentially altered in PLum-AI cells as compared to PLum-AD cells (45 increased and 54 decreased). Principal component analysis (PCA) revealed that the two different cell lines clearly separated apart, indicating a significant proteome expression difference between them. Four of the proteins (vimentin, catalase, EpCAM, and caspase 3) that were differentially expressed in PLum-AI cells compared to PLum-AD cells were subjected to biochemical validation by Western blotting. Biological process gene ontology (GO) analysis of the differentially expressed proteins demonstrated enrichment of biological functions and pathways in PLum-AI cells that are central to PI3 kinase and androgen receptor pathways. Besides, other relevant biological processes that are enriched in PLum-AI cells included cell adhesion and cell migration processes, cell and DNA damage, apoptosis, and cell cycle regulation. Conclusions: Our protein expression analysis of a murine in vitro model of PC progression identified differential protein spots that denote this progression and that comprise high-potential targets for early treatment of PC with a personalized patient-specific approach. Efforts are underway to functionally assess the potential roles of these proteins as therapeutic targets for PC progression.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-10
      DOI: 10.3390/jpm10030083
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 84: Optimising Seniors’ Metabolism of Medications
           and Avoiding Adverse Drug Events Using Data on How Metabolism by Their
           P450 Enzymes Varies with Ancestry and Drug–Drug and Drug–Drug–Gene

    • Authors: Roger E. Thomas
      First page: 84
      Abstract: Many individuals ≥65 have multiple illnesses and polypharmacy. Primary care physicians prescribe >70% of their medications and renew specialists’ prescriptions. Seventy-five percent of all medications are metabolised by P450 cytochrome enzymes. This article provides unique detailed tables how to avoid adverse drug events and optimise prescribing based on two key databases. DrugBank is a detailed database of 13,000 medications and both the P450 and other complex pathways that metabolise them. The Flockhart Tables are detailed lists of the P450 enzymes and also include all the medications which inhibit or induce metabolism by P450 cytochrome enzymes, which can result in undertreatment, overtreatment, or potentially toxic levels. Humans have used medications for a few decades and these enzymes have not been subject to evolutionary pressure. Thus, there is enormous variation in enzymatic functioning and by ancestry. Differences for ancestry groups in genetic metabolism based on a worldwide meta-analysis are discussed and this article provides advice how to prescribe for individuals of different ancestry. Prescribing advice from two key organisations, the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium is summarised. Currently, detailed pharmacogenomic advice is only available in some specialist clinics in major hospitals. However, this article provides detailed pharmacogenomic advice for primary care and other physicians and also physicians working in rural and remote areas worldwide. Physicians could quickly search the tables for the medications they intend to prescribe.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-11
      DOI: 10.3390/jpm10030084
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 85: Current Biomarkers for Alzheimer’s Disease:
           From CSF to Blood

    • Authors: Kun Zou, Mohammad Abdullah, Makoto Michikawa
      First page: 85
      Abstract: Alzheimer’s disease (AD) is the most common cause of dementia and affects a large portion of the elderly population worldwide. Currently, a diagnosis of AD depends on the clinical symptoms of dementia, magnetic resonance imaging to determine brain volume, and positron emission tomography imaging to detect brain amyloid or tau deposition. The best characterized biological fluid markers for AD are decreased levels of amyloid β-protein (Aβ) 42 and increased levels of phosphorylated tau and total tau in cerebrospinal fluid (CSF). However, less invasive and easily detectable biomarkers for the diagnosis of AD, especially at the early stage, are still under development. Here, we provide an overview of various biomarkers identified in CSF and blood for the diagnostics of AD over the last 25 years. CSF biomarkers that reflect the three hallmarks of AD, amyloid deposition, neurofibrillary tangles, and neurodegeneration, are well established. Based on the need to start treatment in asymptomatic people with AD and to screen for AD risk in large numbers of young, healthy individuals, the development of biomarkers for AD is shifting from CSF to blood. Elements of the core pathogenesis of AD in blood, including Aβ42, tau proteins, plasma proteins, or lipids have shown their usefulness and capabilities in AD diagnosis. We also highlight some novel identified blood biomarkers (including Aβ42/Aβ43, p-tau 181, Aβ42/APP669-711, structure of Aβ in blood, and flotillin) for AD.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-12
      DOI: 10.3390/jpm10030085
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 86: Precision Telemedicine through Crowdsourced
           Machine Learning: Testing Variability of Crowd Workers for Video-Based
           Autism Feature Recognition

    • Authors: Peter Washington, Emilie Leblanc, Kaitlyn Dunlap, Yordan Penev, Aaron Kline, Kelley Paskov, Min Woo Sun, Brianna Chrisman, Nathaniel Stockham, Maya Varma, Catalin Voss, Nick Haber, Dennis P. Wall
      First page: 86
      Abstract: Mobilized telemedicine is becoming a key, and even necessary, facet of both precision health and precision medicine. In this study, we evaluate the capability and potential of a crowd of virtual workers—defined as vetted members of popular crowdsourcing platforms—to aid in the task of diagnosing autism. We evaluate workers when crowdsourcing the task of providing categorical ordinal behavioral ratings to unstructured public YouTube videos of children with autism and neurotypical controls. To evaluate emerging patterns that are consistent across independent crowds, we target workers from distinct geographic loci on two crowdsourcing platforms: an international group of workers on Amazon Mechanical Turk (MTurk) (N = 15) and Microworkers from Bangladesh (N = 56), Kenya (N = 23), and the Philippines (N = 25). We feed worker responses as input to a validated diagnostic machine learning classifier trained on clinician-filled electronic health records. We find that regardless of crowd platform or targeted country, workers vary in the average confidence of the correct diagnosis predicted by the classifier. The best worker responses produce a mean probability of the correct class above 80% and over one standard deviation above 50%, accuracy and variability on par with experts according to prior studies. There is a weak correlation between mean time spent on task and mean performance (p= 0.358, p = 0.005). These results demonstrate that while the crowd can produce accurate diagnoses, there are intrinsic differences in crowdworker ability to rate behavioral features. We propose a novel strategy for recruitment of crowdsourced workers to ensure high quality diagnostic evaluations of autism, and potentially many other pediatric behavioral health conditions. Our approach represents a viable step in the direction of crowd-based approaches for more scalable and affordable precision medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-13
      DOI: 10.3390/jpm10030086
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 87: The Blood Cytokine Profile of Young People with
           Early Ischemic Heart Disease Comorbid with Abdominal Obesity

    • Authors: Yulia I. Ragino, Veronika I. Oblaukhova, Yana V. Polonskaya, Natalya A. Kuzminykh, Liliya V. Shcherbakova, Elena V. Kashtanova
      First page: 87
      Abstract: Objective: The aim was to study the blood cytokine/chemokine profile of 25–44-year-old people with early ischemic heart disease (IHD) comorbid with abdominal obesity (AO). Methods: A cross-sectional medical examination of subjects in Novosibirsk, Russia, was conducted after random sampling of the above age group. A total of 1457 subjects, 804 females and 653 males, were analyzed. The epidemiological diagnosis of IHD was made in accordance with 17 validated and functional criteria, employing exercise ECG for confirmation. Simultaneous quantitative analyses of 41 cytokines/chemokines in blood serum were performed by a multiplex assay using the HCYTMAG-60K-PX41 panel (MILLIPLEX MAP) on a Luminex 20 MAGPIX flow cytometer, with additional ELISA testing. Results: Flt3 ligand, GM-CSF, and MCP-1 were significantly associated with the relative risk of early IHD. In the presence of AO, GM-CSF, MCP-1 and IL-4 also significantly correlated with the relative risk of early IHD. By univariate regression analysis, the relative risk of early IHD was associated with lowered blood concentrations of Flt3 ligand, whereas the relative risk of early IHD in the presence of AO was associated with lowered blood concentrations of GM-CSF. Employing multivariable regression analysis, only lower blood levels of Flt3 ligand were associated with a relative risk of early IHD, whereas the relative risk of early IHD in the presence of AO was limited to lower levels of IL-4. Conclusion: Findings related to Flt3 ligand, GM-CSF, and IL-4 are consistent with the international literature. Results from the present study are partly confirmative and partly hypothesis generating.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-13
      DOI: 10.3390/jpm10030087
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 88: Immunotherapy in Corticotroph and Lactotroph
           Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the

    • Authors: Camille Duhamel, Mirela Diana Ilie, Henri Salle, Adjoa Sika Nassouri, Stephan Gaillard, Elise Deluche, Richard Assaker, Laurent Mortier, Christine Cortet, Gérald Raverot
      First page: 88
      Abstract: Once temozolomide has failed, no other treatment is recommended for pituitary carcinomas and aggressive pituitary tumors. Recently, the use of immune checkpoint inhibitors (ICIs) has raised hope, but so far, only one corticotroph carcinoma and one aggressive corticotroph tumor treated with immunotherapies have been reported in the literature. Here, we present two cases, one corticotroph carcinoma and one aggressive prolactinoma (the first one reported in the literature) treated with ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every three weeks, followed by maintenance treatment with nivolumab (3 mg/kg every 2 weeks) in the case of the corticotroph carcinoma, and we compare them with the two previously reported cases. Patient #1 presented a biochemical partial response (plasma ACTH decreased from 13,813 to 841 pg/mL) and dissociated radiological response to the combined ipilimumab and nivolumab—the pituitary mass decreased from 37 × 32 × 41 to 29 × 23 × 42 mm, and the pre-existing liver metastases decreased in size (the largest one from 45 to 14 mm) or disappeared, while a new 11-mm liver metastasis appeared. The maintenance nivolumab (21 cycles) resulted in a stable disease for the initial liver metastases, and in progressive disease for the newly appeared metastasis (effectively treated with radiofrequency ablation) and the pituitary mass. Patient #2 presented radiological and biochemical progressive disease after two cycles of ICIs—the pituitary mass increased from 38 × 42 × 26 to 53 × 57 × 44 mm, and the prolactin levels increased from 4410 to 9840 ng/mL. In conclusion, ICIs represent a promising therapeutic option for aggressive pituitary tumors and carcinomas. The identification of subgroups of responders will be key.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-13
      DOI: 10.3390/jpm10030088
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 89: Resting-State Isolated Effective Connectivity of
           the Cingulate Cortex as a Neurophysiological Biomarker in Patients with
           Severe Treatment-Resistant Schizophrenia

    • Authors: Masataka Wada, Shinichiro Nakajima, Ryosuke Tarumi, Fumi Masuda, Takahiro Miyazaki, Sakiko Tsugawa, Kamiyu Ogyu, Shiori Honda, Karin Matsushita, Yudai Kikuchi, Shinya Fujii, Daniel M. Blumberger, Zafiris J. Daskalakis, Masaru Mimura, Yoshihiro Noda
      First page: 89
      Abstract: Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t45 = 7.659, p = 0.008) and theta (t45 = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-14
      DOI: 10.3390/jpm10030089
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 90: Behavioral and Psychological Symptoms of Dementia
           (BPSD): Clinical Characterization and Genetic Correlates in an Italian
           Alzheimer’s Disease Cohort

    • Authors: Scassellati, Ciani, Maj, Geroldi, Zanetti, Gennarelli, Bonvicini
      First page: 90
      Abstract: Background: The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer’s Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified. Purpose. To characterize our Italian AD cohort according to specific BPSD symptoms as well as to endophenotypes. To evaluate the associations between the considered BPSD traits and COMT, MTHFR, and APOE genetic variants. Methods. AD patients (n = 362) underwent neuropsychological examination and genotyping. BPSD were assessed with the Neuropsychiatric Inventory scale. Results. APOE and MTHFR variants were significantly associated with specific single BPSD symptoms. Furthermore, “Psychosis” and “Hyperactivity” resulted in the most severe endophenotypes, with APOE and MTHFR implicated as both single risk factors and “genexgene” interactions. Conclusions. We strongly suggest the combined use of both BPSD single symptoms/endophenotypes and the “genexgene” interactions as valid strategies for expanding the knowledge about the BPSD aetiopathogenetic mechanisms.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-14
      DOI: 10.3390/jpm10030090
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 91: Changes in the Diversity of Human Skin Microbiota
           to Cosmetic Serum Containing Prebiotics: Results from a Randomized
           Controlled Trial

    • Authors: Ki-Bae Hong, Yang Hee Hong, Eun Young Jung, Kyungae Jo, Hyung Joo Suh
      First page: 91
      Abstract: Prebiotic treatment may rebalance the skin microbiota by regulating the growth of harmful and beneficial microorganisms. In this randomized, double-blind, placebo-controlled clinical trial (N = 60), we evaluated the effects of a cosmetic serum containing galacto-oligosaccharides (GOS) on the balance of the skin microbiota by measuring various skin parameters. The skin water-holding capacity between the control (ND) and experimental (NF) groups was significantly different after 8 weeks of serum treatment (p < 0.05). Similarly, changes in transepidermal water loss (TEWL) and the erythema index in the ND and NF groups were significantly different (p < 0.05). Furthermore, the wrinkle depth and Staphylococcus aureus population decreased in the NF group compared with those in the ND group (p < 0.05). The mean form factor, Shannon index, and Pediococcus population were significantly increased in the post-NF group compared with those in the post-ND group (p < 0.05). Finally, in the ND group, water-holding capacity was positively correlated with Enhydrobacter, whereas Enterobacteriaceae was negatively correlated with TEWL in the NF group. These results suggest that GOS inhibit the growth of harmful skin microbes and increase the population of beneficial microbes.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-17
      DOI: 10.3390/jpm10030091
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 92: Personalized Dental Medicine: Impact of Intraoral
           and Extraoral Clinical Variables on the Precision and Efficiency of
           Intraoral Scanning

    • Authors: César Martínez-Rodríguez, Junco-Plana Patricia, Ortega-Aranegui Ricardo, Iglesias-Linares Alejandro
      First page: 92
      Abstract: (1) Objectives: The aim is to measure the influence of different intraoral (crowding and molar inclination) and extraoral (surface material and ambient light) conditions on the efficacy and efficiency of intraoral scanning. (2) Methods: In a controlled in vitro experimental study, the samples were divided into six groups showing two types of intraoral conditions—lower incisor crowding (groups 1–3) and lower molar mesial tipping (groups 4–6). Each modified model was replicated using three types of materials with different light-absorption properties (n = 18 models). Each sample was scanned 30 times at light intensities of 0.0, 1800, or 3600 l×, yielding 3240 scans. Scanning efficiency (digital acquisition; scanning chair-time; and scanning failures) and scanning efficacy (undetected volume) were assessed using virtual superimpositions and Mecano Equate software. The intra- and interobserver error and reliability of the method were calculated and data analyses were performed using the t-test, paired t-test, and one-way analysis of variance (p < 0.05). (3) Results: Digital acquisition was influenced by the degree of crowding and molar inclination (p < 0.05). The scanning surface material affected the efficacy and efficiency, which were lower with a calcium sulfate hemihydrate A modified compound scanning surface (p < 0.05). Higher intensities of ambient light in the scanning room were associated with reduced scanning efficacy (p < 0.05). Moreover, the scanner showed greater amounts of undetected volume as the degrees of crowding and mesial tipping of the lower second molar increased over 25°, with mean error values of 0.97 mm3 and 1.12 mm3, respectively. (4) Conclusions: For scanning procedures employing digital acquisition, differences in the degrees of crowding and mesial tipping of the lower second molar, scanning surface material, and external light source intensity influence the efficacy and efficiency of the scanning procedures, scanning chair-time, scanning failures, and undetected volume.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-17
      DOI: 10.3390/jpm10030092
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 93: Amerindian Ancestry Influences Genetic
           Susceptibility to Chronic Obstructive Pulmonary Disease

    • Authors: Díaz-Peña, Boekstegers, Silva, Jaime, Hosgood III, Miravitlles, Agustí, Lorenzo Bermejo, Olloquequi
      First page: 93
      Abstract: The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5×10−4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10−3 to 3.77×10−8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-18
      DOI: 10.3390/jpm10030093
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 94: Clonal Hematopoiesis of Indeterminate Potential: A
           Multidisciplinary Challenge in Personalized Hematology

    • Authors: Gregor Hoermann, Georg Greiner, Andrea Griesmacher, Peter Valent
      First page: 94
      Abstract: Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition that represents a potential pre-phase of hematologic neoplasm. Next-generation sequencing (NGS) is used to detect and monitor clonal hematopoiesis, and the spectrum of mutations substantially overlaps with that of myeloid neoplasms with DNMT3A, TET2, ASXL1, and JAK2 being the most frequently mutated. While, in general, the risk of progression to an overt myeloid neoplasm is only modest, the progression risk increases in patients with unexplained cytopenia or multiple mutations. In addition, CHIP represents a previously unrecognized major risk factor for atherosclerosis and cardiovascular disease (CVD), including coronary heart disease, degenerative aortic valve stenosis, and chronic heart failure; and a causative role of CHIP in the development of CVD has been demonstrated in vitro and in vivo. The management of patients with CHIP is a rapidly emerging topic in personalized medicine, as NGS has become widely available for clinical medicine. It requires a highly multidisciplinary setting, including hematology/oncology, cardiology, (clinical) pathology, and genetics for individualized guidance. Further research is urgently needed to provide robust evidence for future guidelines and recommendations on the management of patients with CHIP in the era of personalized medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-20
      DOI: 10.3390/jpm10030094
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 95: CASTER: Cross-Sectional Asthma STEroid Response

    • Authors: Alvin T. Kho, Joanne Sordillo, Ann Chen Wu, Michael H. Cho, Sunita Sharma, Anshul Tiwari, Jessica Lasky-Su, Scott T. Weiss, Kelan G. Tantisira, Michael J. McGeachie
      First page: 95
      Abstract: Asthma patient response to inhaled corticosteroids (ICS) is variable and difficult to quantify. We aimed to define a measure of steroid response suitable for pharmacogenetic research in longitudinal and cross-sectional cohorts. Using longitudinal data from the Childhood Asthma Management Program (CAMP) asthma cohort, we defined the Cross-sectional Asthma STEroid Response (CASTER) measure in cross-sectional data. We then applied this to cross-sectional slices of four independent asthma cohorts: The Improving Asthma Control Trial (IMPACT), the Salmeterol or Corticosteroids Study (SOCS), the Pediatric Asthma Controller Trial (PACT), and the Genetics of Asthma in Costa Rica Study (GACRS). CASTER achieved high accuracy on the childhood asthma cohorts: GACRS, PACT, and also on cross-sectional data from CAMP (AUCs 82%, 71%, 63%, respectively). This demonstrates that select cross-sectional clinical information is sufficient to identify good and poor responders to ICS treatment in childhood asthma. Thus, CASTER represents a major improvement in the usability and applicability of steroid response measures in asthma research.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-20
      DOI: 10.3390/jpm10030095
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 96: Prediction of Coronary Artery Calcium Score Using
           Machine Learning in a Healthy Population

    • Authors: Jongseok Lee, Jae-Sung Lim, Younggi Chu, Chang Hee Lee, Ohk-Hyun Ryu, Hyun Hee Choi, Yong Soon Park, Chulho Kim
      First page: 96
      Abstract: Background: Coronary artery calcium score (CACS) is a reliable predictor for future cardiovascular disease risk. Although deep learning studies using computed tomography (CT) images to predict CACS have been reported, no study has assessed the feasibility of machine learning (ML) algorithms to predict the CACS using clinical variables in a healthy general population. Therefore, we aimed to assess whether ML algorithms other than binary logistic regression (BLR) could predict high CACS in a healthy population with general health examination data. Methods: This retrospective observational study included participants who had regular health screening including coronary CT angiography. High CACS was defined by the Agatston score ≥ 100. Univariable and multivariable BLR was performed to assess predictors for high CACS in the entire dataset. When performing ML prediction for high CACS, the dataset was randomly divided into a training and test dataset with a 7:3 ratio. BLR, catboost, and xgboost algorithms with 5-fold cross-validation and grid search technique were used to find the best performing classifier. Performance comparison of each ML algorithm was evaluated with the area under the receiver operating characteristic (AUROC) curve. Results: A total of 2133 participants were included in the final analysis. Mean age and proportion of male sex were 55.4 ± 11.3 years and 1483 (69.5%), respectively. In multivariable BLR analysis, age (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.10–1.15, p < 0.001), male sex (OR, 2.91; 95% CI, 1.57–5.38, p < 0.001), systolic blood pressure (OR, 1.02; 95% CI, 1.00–1.03, p = 0.019), and low-density lipoprotein cholesterol (OR, 1.00; 95% CI, 0.99–1.00, p = 0.047) were significant predictors for high CACS. Performance in predicting high CACS of xgboost was AUROC of 0.823, followed by catboost (0.750) and BLR (0.585). The comparison of AUROC between xgboost and BLR was significant (p for AUROC comparison < 0.001). Conclusions: Xgboost ML algorithm was found to be a more reliable predictor of CACS in healthy participants compared to the BLR algorithm. ML algorithms may be useful for predicting CACS with only laboratory data in healthy participants.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-20
      DOI: 10.3390/jpm10030096
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 97: Benefit of Wearing an Activity Tracker in

    • Authors: Marjolein Drent, Marjon Elfferich, Ellen Breedveld, Jolanda De Vries, Bert Strookappe
      First page: 97
      Abstract: Sarcoidosis causes many disabling symptoms, including fatigue and exercise limitations, which have been shown to improve by physical activity programs. The aim of this study was to estimate the effect of continuous activity monitoring using an electronic activity tracker (AT) on exercise performance and fatigue of sarcoidosis patients, compared to controls (cohort study), and the effect of additional personal coaching (randomized trial) over a period of 3 months. Fifty-four sarcoidosis patients received an AT (Group Ia: 27 with coaching and Group Ib: 27 without). A historical group of sarcoidosis patients (Group II; n = 41) who did not follow a physical activity program served as controls. Exercise performance of patients wearing an AT (Group I) improved compared with controls (Group II), including the 6MWD, % predicted (∆4.4 ± 9.1 versus ∆0.7 ± 5.0, respectively), and fatigue levels decreased (∆−3.9 ± 5.7 versus ∆−1.8 ± 5.3). Patients with coaching (Group Ia) showed greater improvement of exercise capacity over time than patients without coaching (Group Ib) as shown by the Steep Ramp Test results (watts: ∆20.2 ± 33.8 versus ∆5.7 ± 26.4; and SRT, VO2max, % predicted: ∆1.6 ± 2.6 versus ∆0.7 ± 2.3). Sarcoidosis patients wearing an AT achieved improvement of exercise performance and reduction of fatigue. We therefore recommend encouraging sarcoidosis patients to wear an AT to stimulate physical activity and reduce fatigue. The additional benefit of coaching needs to be explored in future studies.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-22
      DOI: 10.3390/jpm10030097
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 98: Circulating MicroRNAs as Prognostic and
           Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

    • Authors: Veronica Zelli, Chiara Compagnoni, Roberta Capelli, Katia Cannita, Tina Sidoni, Corrado Ficorella, Carlo Capalbo, Francesca Zazzeroni, Alessandra Tessitore, Edoardo Alesse
      First page: 98
      Abstract: Breast cancer (BC) is a common and heterogeneous disease, of which six molecular subtypes, characterized by different biological features and clinical outcomes, were described. The identification of additional biomarkers able to further connote and distinguish the different BC subtypes is essential to improve the diagnostic, prognostic and therapeutic strategies in BC patients. MicroRNAs (miRNAs) are short non-coding RNA involved in several physiological and pathological processes, including cancer development and progression. In particular, circulating miRNAs, which can be found in an adequately stable structure in serum/plasma of cancer patients, are emerging as very promising non-invasive biomarkers. Several studies have analyzed the potential role of circulating miRNAs as prognostic and therapeutic markers in BC. In the present review we describe circulating miRNAs, identified as putative biomarker in BC, with special reference to different BC molecular subtypes.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-22
      DOI: 10.3390/jpm10030098
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 99: Diagnostic and Prognostic Significance of MiR-150
           in Colorectal Cancer: A Systematic Review and Meta-Analysis

    • Authors: Daniel Sur, Claudia Burz, Shanthi Sabarimurugan, Alexandru Irimie
      First page: 99
      Abstract: Although treatment options have improved, the survival and quality of life of colorectal cancer (CRC) patients remain dismal. Therefore, significant biomarker prediction may help to improve colorectal cancer patient’s prognosis profile. MiRNAs have come as an option because of their essential role in cancer initiation and progression by regulating several molecular processes. MiR-150 has different roles in cancer, but its function in CRC is still ambiguous. We undertook a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) research criteria by interrogating several databases in order to assess the diagnostic accuracy and prognostic value of miR-150. Additionally, was scanned for possible trials. The literature was screened from inception to February 2020. A total of 12 out of 70 full-text articles were included in the meta-analysis. Among these, nine studies were included for diagnostic accuracy, and the remaining three were considered for prognostic significance of miR-150. With our results, miR-150 is an appropriate diagnostic biomarker, especially in serum and plasma, while the prognostic value of miR-150 was not statistically significant. The present study findings suggest that miR-150 has high specificity and sensitivity values as a potential diagnostic biomarker in colorectal cancer patients.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-24
      DOI: 10.3390/jpm10030099
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 100: Analysis of APPL1 Gene Polymorphisms in Patients
           with a Phenotype of Maturity Onset Diabetes of the Young

    • Authors: Dinara E. Ivanoshchuk, Elena V. Shakhtshneider, Oksana D. Rymar, Alla K. Ovsyannikova, Svetlana V. Mikhailova, Pavel S. Orlov, Yuliya I. Ragino, Mikhail I. Voevoda
      First page: 100
      Abstract: The APPL1 gene encodes a protein mediating the cross-talk between adiponectin and insulin signaling. Recently, it was found that APPL1 mutations can cause maturity onset diabetes of the young, type 14. Here, an analysis of APPL1 was performed in patients with a maturity-onset diabetes of the young (MODY) phenotype, and prevalence of these mutations was estimated in a Russian population, among type 2 diabetes mellitus (T2DM) and MODY patients. Whole-exome sequencing or targeted sequencing was performed on 151 probands with a MODY phenotype, with subsequent association analysis of one of identified variants, rs11544593, in a white population of Western Siberia (276 control subjects and 169 T2DM patients). Thirteen variants were found in APPL1, three of which (rs79282761, rs138485817, and rs11544593) are located in exons. There were no statistically significant differences in the frequencies of rs11544593 alleles and genotypes between T2DM patients and the general population. In the MODY group, AG rs11544593 genotype carriers were significantly more frequent (AG vs. AA + GG: odds ratio 1.83, confidence interval 1.15–2.90, p = 0.011) compared with the control group. An association of rs11544593 with blood glucose concentration was revealed in the MODY group. The genotyping data suggest that rs11544593 may contribute to carbohydrate metabolism disturbances.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-25
      DOI: 10.3390/jpm10030100
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 101: Molecular and Cellular Mechanisms Affected in ALS

    • Authors: Laura Le Gall, Ekene Anakor, Owen Connolly, Udaya Geetha Vijayakumar, William J. Duddy, Stephanie Duguez
      First page: 101
      Abstract: Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-25
      DOI: 10.3390/jpm10030101
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 102: Implication of Aging Related Chronic
           Neuroinflammation on COVID-19 Pandemic

    • Authors: Paola Bossù, Elisa Toppi, Valentina Sterbini, Gianfranco Spalletta
      First page: 102
      Abstract: SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-26
      DOI: 10.3390/jpm10030102
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 103: Implementation and Continuous Monitoring of an
           Electronic Health Record Embedded Readmissions Clinical Decision Support

    • Authors: David Gallagher, Congwen Zhao, Amanda Brucker, Jennifer Massengill, Patricia Kramer, Eric G. Poon, Benjamin A. Goldstein
      First page: 103
      Abstract: Unplanned hospital readmissions represent a significant health care value problem with high costs and poor quality of care. A significant percentage of readmissions could be prevented if clinical inpatient teams were better able to predict which patients were at higher risk for readmission. Many of the current clinical decision support models that predict readmissions are not configured to integrate closely with the electronic health record or alert providers in real-time prior to discharge about a patient’s risk for readmission. We report on the implementation and monitoring of the Epic electronic health record—“Unplanned readmission model version 1”—over 2 years from 1/1/2018–12/31/2019. For patients discharged during this time, the predictive capability to discern high risk discharges was reflected in an AUC/C-statistic at our three hospitals of 0.716–0.760 for all patients and 0.676–0.695 for general medicine patients. The model had a positive predictive value ranging from 0.217–0.248 for all patients. We also present our methods in monitoring the model over time for trend changes, as well as common readmissions reduction strategies triggered by the score.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-26
      DOI: 10.3390/jpm10030103
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 104: Evaluation of ML-Based Clinical Decision Support
           Tool to Replace an Existing Tool in an Academic Health System: Lessons

    • Authors: Myung Woo, Brooke Alhanti, Sam Lusk, Felicia Dunston, Stephen Blackwelder, Kay S. Lytle, Benjamin A. Goldstein, Armando Bedoya
      First page: 104
      Abstract: There is increasing application of machine learning tools to problems in healthcare, with an ultimate goal to improve patient safety and health outcomes. When applied appropriately, machine learning tools can augment clinical care provided to patients. However, even if a model has impressive performance characteristics, prospectively evaluating and effectively implementing models into clinical care remains difficult. The primary objective of this paper is to recount our experiences and challenges in comparing a novel machine learning-based clinical decision support tool to legacy, non-machine learning tools addressing potential safety events in the hospitals and to summarize the obstacles which prevented evaluation of clinical efficacy of tools prior to widespread institutional use. We collected and compared safety events data, specifically patient falls and pressure injuries, between the standard of care approach and machine learning (ML)-based clinical decision support (CDS). Our assessment was limited to performance of the model rather than the workflow due to challenges in directly comparing both approaches. We did note a modest improvement in falls with ML-based CDS; however, it was not possible to determine that overall improvement was due to model characteristics.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-27
      DOI: 10.3390/jpm10030104
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 105: Stickler Syndrome: A Review of Clinical
           Manifestations and the Genetics Evaluation

    • Authors: Megan Boothe, Robert Morris, Nathaniel Robin
      First page: 105
      Abstract: Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for these patients. Systemic findings are also common, with craniofacial, skeletal, and auditory systems often involved. SS is genotypically and phenotypically heterogenous, which can make recognizing and correctly diagnosing individuals difficult. Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members. Here we review common clinical manifestation of SS and genetic tests frequently ordered as part of the SS evaluation.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-27
      DOI: 10.3390/jpm10030105
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 106: Patient General Condition at Diagnosis: A
           Systematic Evaluation for Adults Diagnosed with Hematologic Malignancies

    • Authors: Fernando Ramos, Paola González-Carmona, María Isabel Porras-Guerra, Sonia Jiménez-Mola, Ana María Martínez-Peláez, Agustín Blanco-Cabielles, Saray Conde, Abdolah Ahmadi, Marta Castellanos, Seila Cerdá, Natalia de las Heras, Elisa Menéndez, Fernando Escalante, Silvia Fernández-Ferrero, Tamara Lado, Violeta Martínez-Robles, Filomeno Rondón, Irene Padilla, María Jesús Vidal, María Lavinia Villalobos, Saad Yacoubi, Francisco Javier Idoate-Gil, José Antonio Rodríguez-García
      First page: 106
      Abstract: Several societies have published recommendations for evaluating older adults with cancer in standard conditions. It is vital to assure a proper systematic patient condition evaluation, not only in the oldest (geriatric assessment) but in all adult patients. We have investigated the feasibility of a systematic evaluation of the general condition of all patients diagnosed with hematologic malignancies, and the degree of acceptance by the clinical team, in a prospective cohort of 182 consecutive adults, by using the ECOG performance status scale (ECOG, age 18 and over, 18+), Lee Index for Older Adults (LEE, 50+), Geriatric Assessment in Hematology (GAH, 65+), and the Comprehensive Geriatric Assessment (CGA, 75+). Clinical team acceptance was analyzed with a visual analogue scale, and the objective feasibility was calculated as the proportion of patients that could be finally evaluated with each tool. Acceptance was high, but the objective feasibility was progressively lower as the complexity of the different tools increased (ECOG 100%, LEE 99.4%, GAH 93.2%, and CGA 67.9%). LEE and GAH categories showed a weak concordance (Cohen’s Kappa 0.24) that was slight between LEE and CGA (Kappa 0.18). Unexpectedly, we found no significant association between the GAH and CGA categories (p = 0.16). We confirm that a systematic evaluation of all adult patients diagnosed with hematologic malignancies is feasible in daily practice by using an age-adapted approach. Direct comparisons among the different predictive tools in regard to patients’ tolerance to treatments of different intensities must be a priority research subject in the coming years.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-27
      DOI: 10.3390/jpm10030106
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 107: Efficacy of Incremental Next-Generation ALK

    • Authors: László Urbán, Róbert Dóczi, Barbara Vodicska, Dóra Kormos, László Tóth, István Takács, Edit Várkondi, Dóra Tihanyi, Dóra Lakatos, Anna Dirner, István Vályi-Nagy, István Peták
      First page: 107
      Abstract: Background: The anaplastic lymphoma kinase (ALK) gene fusion rearrangement is a potent oncogene, accounting for 2–7% of lung adenocarcinomas, with higher incidence (17–20%) in non-smokers. ALK-positive tumors are sensitive to ALK tyrosine kinase inhibitors (TKIs), thus ALK-positive non-small-cell lung cancer (NSCLC) is currently spearheading precision medicine in thoracic oncology, with three generations of approved ALK inhibitors in clinical practice. However, these treatments are eventually met with resistance. At the molecular level, ALK-positive NSCLC is of the lowest tumor mutational burden, which possibly accounts for the high initial response to TKIs. Nevertheless, TP53 co-mutations are relatively frequent and are associated with adverse outcome of crizotinib treatment, whereas utility of next-generation ALK inhibitors in TP53-mutant tumors is still unknown. Methods: We report the case of an ALK-positive, TP53-mutant NSCLC patient with about five years survival on ALK TKIs with continued next-generation regimens upon progression. Results: The tumor showed progression on crizotinib, but long tumor control was achieved following the incremental administration of next-generation ALK inhibitors, despite lack of evident resistance mechanisms. Conclusion: TP53 status should be taken into consideration when selecting ALK-inhibitor treatment for personalized therapies. In TP53-mutant tumors, switching TKI generations may overcome treatment exhaustion even in the absence of ALK-dependent resistance mechanisms.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-28
      DOI: 10.3390/jpm10030107
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 108: Pharmacogenomics to Predict Tumor Therapy
           Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes

    • Authors: Viktor Hlaváč, Petr Holý, Pavel Souček
      First page: 108
      Abstract: Pharmacogenomics is an evolving tool of precision medicine. Recently, due to the introduction of next-generation sequencing and projects generating “Big Data”, a plethora of new genetic variants in pharmacogenes have been discovered. Cancer resistance is a major complication often preventing successful anticancer treatments. Pharmacogenomics of both somatic mutations in tumor cells and germline variants may help optimize targeted treatments and improve the response to conventional oncological therapy. In addition, integrative approaches combining copy number variations and long noncoding RNA profiling with germline and somatic variations seem to be a promising approach as well. In pharmacology, expression and enzyme activity are traditionally the more studied aspects of ATP-binding cassette transporters and cytochromes P450. In this review, we briefly introduce the field of pharmacogenomics and the advancements driven by next-generation sequencing and outline the possible roles of genetic variation in the two large pharmacogene superfamilies. Although the evidence needs further substantiation, somatic and copy number variants as well as rare variants and common polymorphisms in these genes could all affect response to cancer therapy. Regulation by long noncoding RNAs has also been shown to play a role. However, in all these areas, more comprehensive studies on larger sets of patients are needed.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-08-28
      DOI: 10.3390/jpm10030108
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 109: Sestrin2 Expression Has Regulatory Properties and
           Prognostic Value in Lung Cancer

    • Authors: Hee Sung Chae, Minchan Gil, Subbroto Kumar Saha, Hee Jeung Kwak, Hwan-Woo Park, Balachandar Vellingiri, Ssang-Goo Cho
      First page: 109
      Abstract: Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-01
      DOI: 10.3390/jpm10030109
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 110: Induction of Micronuclei in Cervical Cancer
           Treated with Radiotherapy

    • Authors: Daijiro Kobayashi, Takahiro Oike, Kazutoshi Murata, Daisuke Irie, Yuka Hirota, Hiro Sato, Atsushi Shibata, Tatsuya Ohno
      First page: 110
      Abstract: Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4′,6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16–327) versus 28 (range, 0–61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0–30) versus 12 (range, 2–30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-03
      DOI: 10.3390/jpm10030110
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 111: Advances in Genetic Characterization and
           Genotype–Phenotype Correlation of Duchenne and Becker Muscular Dystrophy
           in the Personalized Medicine Era

    • Authors: Omar Sheikh, Toshifumi Yokota
      First page: 111
      Abstract: Currently, Duchenne muscular dystrophy (DMD) and the related condition Becker muscular dystrophy (BMD) can be usually diagnosed using physical examination and genetic testing. While BMD features partially functional dystrophin protein due to in-frame mutations, DMD largely features no dystrophin production because of out-of-frame mutations. However, BMD can feature a range of phenotypes from mild to borderline DMD, indicating a complex genotype–phenotype relationship. Despite two mutational hot spots in dystrophin, mutations can arise across the gene. The use of multiplex ligation amplification (MLPA) can easily assess the copy number of all exons, while next-generation sequencing (NGS) can uncover novel or confirm hard-to-detect mutations. Exon-skipping therapy, which targets specific regions of the dystrophin gene based on a patient’s mutation, is an especially prominent example of personalized medicine for DMD. To maximize the benefit of exon-skipping therapies, accurate genetic diagnosis and characterization including genotype–phenotype correlation studies are becoming increasingly important. In this article, we present the recent progress in the collection of mutational data and optimization of exon-skipping therapy for DMD/BMD.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-03
      DOI: 10.3390/jpm10030111
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 112: Immunohistochemical Characterization of Immune
           Infiltrate in Tumor Microenvironment of Glioblastoma

    • Authors: Hassan Rahimi Koshkaki, Simone Minasi, Alessio Ugolini, Gianluca Trevisi, Chiara Napoletano, Ilaria G. Zizzari, Marco Gessi, Felice Giangaspero, Annunziato Mangiola, Marianna Nuti, Francesca R. Buttarelli, Aurelia Rughetti
      First page: 112
      Abstract: Background: Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. Methods: The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. Results: CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. Conclusion: Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-03
      DOI: 10.3390/jpm10030112
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 113: A Genotyping/Phenotyping Approach with Careful
           Clinical Monitoring to Manage the Fluoropyrimidines-Based Therapy:
           Clinical Cases and Systematic Review of the Literature

    • Authors: Valeria Conti, Emanuela De Bellis, Valentina Manzo, Francesco Sabbatino, Francesco Iannello, Fabrizio Dal Piaz, Viviana Izzo, Bruno Charlier, Berenice Stefanelli, Martina Torsiello, Teresa Iannaccone, Albino Coglianese, Francesca Colucci, Stefano Pepe, Amelia Filippelli
      First page: 113
      Abstract: Fluoropyrimidines (FP) are mainly metabolised by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. FP pharmacogenetics, including four DPYD polymorphisms (DPYD-PGx), is recommended to tailor the FP-based chemotherapy. These polymorphisms increase the risk of severe toxicity; thus, the DPYD-PGx should be performed prior to starting FP. Other factors influence FP safety, therefore phenotyping methods, such as the measurement of 5-fluorouracil (5-FU) clearance and DPD activity, could complement the DPYD-PGx. We describe a case series of patients in whom we performed DPYD-PGx (by real-time PCR), 5-FU clearance and a dihydrouracil/uracil ratio (as the phenotyping analysis) and a continuous clinical monitoring. Patients who had already experienced severe toxicity were then identified as carriers of DPYD variants. The plasmatic dihydrouracil/uracil ratio (by high-performance liquid chromatography (HPLC)) ranged between 1.77 and 7.38. 5-FU clearance (by ultra-HPLC with tandem mass spectrometry) was measured in 3/11 patients. In one of them, it reduced after the 5-FU dosage was halved; in the other case, it remained high despite a drastic dosage reduction. Moreover, we performed a systematic review on genotyping/phenotyping combinations used as predictive factors of FP safety. Measuring the plasmatic 5-FU clearance and/or dihydrouracil/uracil (UH2/U) ratio could improve the predictive potential of DPYD-PGx. The upfront DPYD-PGx combined with clinical monitoring and feasible phenotyping method is essential to optimising FP-based chemotherapy.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-03
      DOI: 10.3390/jpm10030113
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 114: Biomarkers for Alzheimer’s Disease Early

    • Authors: Eva Ausó, Violeta Gómez-Vicente, Gema Esquiva
      First page: 114
      Abstract: Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-04
      DOI: 10.3390/jpm10030114
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 115: The Other Side of Alzheimer’s Disease:
           Influence of Metabolic Disorder Features for Novel Diagnostic Biomarkers

    • Authors: Chiara Argentati, Ilaria Tortorella, Martina Bazzucchi, Carla Emiliani, Francesco Morena, Sabata Martino
      First page: 115
      Abstract: Nowadays, the amyloid cascade hypothesis is the dominant model to explain Alzheimer’s disease (AD) pathogenesis. By this hypothesis, the inherited genetic form of AD is discriminated from the sporadic form of AD (SAD) that accounts for 85–90% of total patients. The cause of SAD is still unclear, but several studies have shed light on the involvement of environmental factors and multiple susceptibility genes, such as Apolipoprotein E and other genetic risk factors, which are key mediators in different metabolic pathways (e.g., glucose metabolism, lipid metabolism, energetic metabolism, and inflammation). Furthermore, growing clinical evidence in AD patients highlighted the presence of affected systemic organs and blood similarly to the brain. Collectively, these findings revise the canonical understating of AD pathogenesis and suggest that AD has metabolic disorder features. This review will focus on AD as a metabolic disorder and highlight the contribution of this novel understanding on the identification of new biomarkers for improving an early AD diagnosis.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-06
      DOI: 10.3390/jpm10030115
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 116: Significance of Blood and Cerebrospinal Fluid
           Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and
           Potential for Clinical Use

    • Authors: Cristina d’Abramo, Luciano D’Adamio, Luca Giliberto
      First page: 116
      Abstract: Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-08
      DOI: 10.3390/jpm10030116
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 117: Influence of SH2B3, MTHFD1L, GGCX, and ITGB3 Gene
           Polymorphisms on theVariability on Warfarin Dosage Requirements and
           Susceptibility to CVD in the Jordanian Population

    • Authors: Laith N. AL-Eitan, Ayah Y. Almasri, Rame H. Khasawneh, Mansour A. Alghamdi
      First page: 117
      Abstract: The purpose of this study was to investigate the effects of the SH2B3, MTHFD1L, GGCX, and ITGB3 gene variants on the efficacy of warfarin treatment and its effects on the risk of cardiovascular disorders in Jordanian patients. The selected genes and their polymorphisms are involved in many Genome-Wide Association Study (GWAS) associated with cardiovascular disease and the variability of warfarin therapy. The current study conducted a genetic association and pharmacogenetics study in (212) Jordanian cardiovascular patients treated with warfarin and (213) healthy controls. DNA extraction and the Mass ARRAY™ system were used to genotype ten selected polymorphisms within four genes (SH2B3, MTHFD1L, GGCX, and ITGB3). This study confirmed a genetic association of MTHFD1L rs6922269 Single Nucleotide Polymorphism (SNP) with warfarin sensitivity during the initial and stabilization phases of treatment. Moreover, this SNP showed significant differences in the initial and maintenance doses of warfarin. This study also found an association between the genetic haplotypes (AGC and GAT) within the SH2B3 gene and responsiveness to warfarin. However, possession of an MTHFD1L rs491552 variant allele was found to affect the outcome measure of the international normalized ratio (INR) during the stabilization phase of warfarin treatment. In contrast, there was no association between all selected SNPs and susceptibility to cardiovascular disorders. This study extends the current understanding of the high variability of the warfarin response, including variability in dose requirements and susceptibility to cardiovascular disease in the Jordanian-Arab population. Other studies on a larger sample and in different ethnic groups could help to better understand the pharmacogenetics of warfarin and its application in personalized medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-09
      DOI: 10.3390/jpm10030117
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 118: Personalized Tests in Paralympic Athletes:
           Aerobic and Anaerobic Performance Profile of Elite Wheelchair Rugby

    • Authors: Giuseppe Marcolin, Nicola Petrone, Michael Benazzato, Francesco Bettella, Angela Gottardi, Luigi Salmaso, Livio Corain, Alfredo Musumeci, Stefano Masiero, Antonio Paoli
      First page: 118
      Abstract: In Paralympic sports, the goal of functional classifications is to minimize the impact of impairment on the outcome of the competition. The present cross-sectional study aimed to investigate aerobic and anaerobic personalized tests in Paralympic athletes and to correlate them with the classification of the international wheelchair rugby federation (IWRF). Sixteen elite players of the Italian wheelchair rugby team volunteered for the study. Aerobic (incremental test to exhaustion) and anaerobic (Wingate 30s all-out test, 5 and 10-meter sprint test, shuttle test, isometric test) sport-performance measurements were correlated singularly or grouped (Z scores) with the classification point. Moreover, a multivariate permutation-based ranking analysis investigated possible differences in the overall level of performance among the adjacent classified groups of players, considering the scores of each test. A statistically significant correlation between the performance parameters and the IWRF functional classification considering both aerobic and anaerobic personalized tests was detected (0.58 ≤ r ≤ 0.88; 0.0260 ≤ p ≤ 0.0001). The multivariate permutation-based ranking analysis showed differences only for the low-pointers versus mid-pointers (p = 0.0195) and high-pointers (p = 0.0075). Although single performance parameters correlated with athletes’ classification point, results of the multivariate permutation-based ranking analysis seem to suggest considering only the most significant anaerobic and sport-specific performance parameters among athletes. These should be combined with the physical assessment and the qualitative observation, which are already part of the classification process to improve its effectiveness.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-09
      DOI: 10.3390/jpm10030118
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 119: Application of Noninvasive Vagal Nerve
           Stimulation to Stress-Related Psychiatric Disorders

    • Authors: James Douglas Bremner, Nil Z. Gurel, Matthew T. Wittbrodt, Mobashir H. Shandhi, Mark H. Rapaport, Jonathon A. Nye, Bradley D. Pearce, Viola Vaccarino, Amit J. Shah, Jeanie Park, Marom Bikson, Omer T. Inan
      First page: 119
      Abstract: Background: Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation. Methods: New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders. Results: This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders. Conclusions: nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-09
      DOI: 10.3390/jpm10030119
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 120: Minimal Residual Disease in Multiple Myeloma:
           State of the Art and Applications in Clinical Practice

    • Authors: Alessandro Gozzetti, Donatella Raspadori, Francesca Bacchiarri, Anna Sicuranza, Paola Pacelli, Ilaria Ferrigno, Dania Tocci, Monica Bocchia
      First page: 120
      Abstract: Novel drugs have revolutionized multiple myeloma therapy in the last 20 years, with median survival that has doubled to up to 8–10 years. The introduction of therapeutic strategies, such as consolidation and maintenance after autologous stem cell transplants, has also ameliorated clinical results. The goal of modern therapies is becoming not only complete remission, but also the deepest possible remission. In this context, the evaluation of minimal residual disease by techniques such as next-generation sequencing (NGS) and next-generation flow (NGF) is becoming part of all new clinical trials that test drug efficacy. This review focuses on minimal residual disease approaches in clinical trials, with particular attention to real-world practices.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-10
      DOI: 10.3390/jpm10030120
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 121: Evaluating the Impact of Telehealth-Based,
           Diabetes Medication Training for Community Health Workers on Glycemic

    • Authors: Casey N. Keegan, Craig A. Johnston, Victor J. Cardenas, Elizabeth M. Vaughan
      First page: 121
      Abstract: Background: Diabetes is a major contributor to morbidity and mortality. Community Health Workers (CHWs) have been instrumental in improving patient outcomes. However, CHW training largely focuses on general diabetes concepts rather than medications. Providing accessible, diabetes medication training for CHWs has the potential to increase patient understanding, personalized care, and adherence, thereby improving outcomes. Objective: To evaluate the impact of a telehealth-based diabetes medication training for CHWs on patient outcomes as measured by HbA1c changes. Methods: We provided a 12-month weekly, telehealth (videoconference) medication training for CHWs who led 6-month diabetes programs for low-income Latino(a)s in community clinics. We measured participant HbA1c (primary outcome), blood pressure, and body mass index (BMI) changes. We evaluated CHW knowledge via two pre/post-tests: medication adverse events/side effects (TEST-1, months 1–6) and dosing, titration, and emergencies (TEST-2, months 7–12). We assessed CHW training application by their ability to identify patient, provider, and healthcare system medication barriers. Results: Participants’ (n = 55) HbA1c improved (9.0% (75 mmol/mol) to 7.8% (62 mmol/mol) (p = 0.001)). Blood pressure and BMI changes were not significant. CHWs improved their knowledge: TEST-1: 10.5-18.2/20.0 (p = 0.002), TEST-2: 10.3–17.3/19.0 (p = 0.0019). CHWs identified 984 patient (n = 610), provider (n = 151), and healthcare system (n = 223) medication barriers during the 12-month training. Conclusions: Providing a telehealth-based, diabetes medication training program for CHWs allowed a personalized approach to identify barriers to care at several levels, which was associated with significant participant HbA1c reductions and improved CHW knowledge. This is a promising cost-effective, culturally sensitive strategy to improve diabetes care. Larger longitudinal evaluations are needed to fully understand the impact of CHW medication training.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-11
      DOI: 10.3390/jpm10030121
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 122: Measuring IGF-1 and IGFBP-3 Profiles in Women
           Seeking Assisted Reproduction; Relationship to Clinical Parameters (Study

    • Authors: John L. Yovich, Syeda Zaidi, Minh D. K. Nguyen, Peter M. Hinchliffe
      First page: 122
      Abstract: This study examines the IGF serum profile (IGF-1, IGFBP-3 and the IGF Ratio) from 1633 women who undertook an Assessment Cycle prior to any treatment by assisted reproduction. The idea is to progressively study the IGF profile with a view to identify those women who may be classified as having adult growth hormone deficiency (AGHD) and who may benefit from specific dynamic endocrinological testing to identify a potential benefit from growth hormone adjuvant treatment. This first study evaluates the IGF profile on clinical parameters, namely age, body mass index (BMI) and stature. The study shows a significant linear reduction in IGF-1 levels across the four age groups (<35 years, 35–39 years, 40–44 years and ≥45 years; p < 0.001). However, there was no variation in IGFBP-3 levels but the IGF Ratio showed a progressive linear elevation with advancing age (p < 0.001). With respect to both BMI and stature, none of the IGF profile parameters showed any variation. We conclude that further studies are warranted to examine the notion of underlying AGHD in the causation of the well-known feature of age-related poor prognosis in assisted reproduction.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-11
      DOI: 10.3390/jpm10030122
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 123: The Genomics and Metagenomics of Asthma Severity
           (GEMAS) Study: Rationale and Design

    • Authors: Javier Perez-Garcia, José M. Hernández-Pérez, Ruperto González-Pérez, Olaia Sardón, Elena Martin-Gonzalez, Antonio Espuela-Ortiz, Elena Mederos-Luis, Ariel Callero, Esther Herrera-Luis, Paula Corcuera, Inmaculada Sánchez-Machín, Paloma Poza-Guedes, Luis Manuel González García, Purificación Ramírez-Martín, Lorenzo Pérez-Negrín, Hemily Izaguirre-Flores, Javier Barrios-Recio, Eva Pérez-Rodríguez, Julia Alcoba-Florez, José A. Cañas, José M. Rodrigo Muñoz, Victoria del Pozo, Javier Korta-Murua, Lina I. Pérez Méndez, Mariano Hernandez-Ferrer, Jesús Villar, Fabian Lorenzo-Diaz, Maria Pino-Yanes
      First page: 123
      Abstract: Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables (p > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls (p < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-11
      DOI: 10.3390/jpm10030123
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 124: Transcript Levels of Aldo-Keto Reductase Family 1
           Subfamily C (AKR1C) Are Increased in Prostate Tissue of Patients with Type
           2 Diabetes

    • Authors: Andras Franko, Lucia Berti, Jörg Hennenlotter, Steffen Rausch, Marcus O. Scharpf, Martin Hrabĕ de Angelis, Arnulf Stenzl, Andreas L. Birkenfeld, Andreas Peter, Stefan Z. Lutz, Hans-Ulrich Häring, Martin Heni
      First page: 124
      Abstract: Aldo-keto reductase family 1 (AKR1) enzymes play a crucial role in diabetic complications. Since type 2 diabetes (T2D) is associated with cancer progression, we investigated the impact of diabetes on AKR1 gene expression in the context of prostate cancer (PCa) development. In this study, we analyzed benign (BEN) prostate and PCa tissue of patients with and without T2D. Furthermore, to replicate hyperglycemia in vitro, we treated the prostate adenocarcinoma cell line PC3 with increasing glucose concentrations. Gene expression was quantified using real-time qPCR. In the prostate tissue of patients with T2D, AKR1C1 and AKR1C2 transcripts were higher compared to samples of patients without diabetes. In PC3 cells, high glucose treatment induced the gene expression levels of AKR1C1, C2, and C3. Furthermore, both in human tissue and in PC3 cells, the transcript levels of AKR1C1, C2, and C3 showed positive associations with oncogenes, which are involved in proliferation processes and HIF1α and NFκB pathways. These results indicate that in the prostate glands of patients with T2D, hyperglycemia could play a pivotal role by inducing the expression of AKR1C1, C2, and C3. The higher transcript level of AKR1C was furthermore associated with upregulated HIF1α and NFκB pathways, which are major drivers of PCa carcinogenesis.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-12
      DOI: 10.3390/jpm10030124
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 125: The Cytokinesis-Block Micronucleus Assay on Human
           Isolated Fresh and Cryopreserved Peripheral Blood Mononuclear Cells

    • Authors: Simon Sioen, Karlien Cloet, Anne Vral, Ans Baeyens
      First page: 125
      Abstract: The cytokinesis-block micronucleus (CBMN) assay is a standardized method used for genotoxicity studies. Conventional whole blood cultures (WBC) are often used for this assay, although the assay can also be performed on isolated peripheral blood mononuclear cell (PBMC) cultures. However, the standardization of a protocol for the PBMC CBMN assay has not been investigated extensively. The aim of this study was to optimize a reliable CBMN assay protocol for fresh and cryopreserved peripheral blood mononuclear cells (PBMCS), and to compare micronuclei (MNi) results between WBC and PBMC cultures. The G0 CBMN assay was performed on whole blood, freshly isolated, and cryopreserved PBMCS from healthy human blood samples and five radiosensitive patient samples. Cells were exposed to 220 kV X-ray in vitro doses ranging from 0.5 to 2 Gy. The optimized PBMC CBMN assay showed adequate repeatability and small inter-individual variability. MNi values were significantly higher for WBC than for fresh PBMCS. Additionally, cryopreservation of PBMCS resulted in a significant increase of MNi values, while different cryopreservation times had no significant impact. In conclusion, our standardized CBMN assay on fresh and cryopreserved PBMCS can be used for genotoxicity studies, biological dosimetry, and radiosensitivity assessment.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-14
      DOI: 10.3390/jpm10030125
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 126: Psychological and Medical Characteristics
           Associated with Non-Adherence to Prescribed Daily Inhaled Corticosteroid

    • Authors: Brett G. Toelle, Guy B. Marks, Stewart M. Dunn
      First page: 126
      Abstract: Medication non-adherence is associated with sub-optimal asthma control. Identification of medical and psychological characteristics associated with non-adherence is important to enable a targeted and personalized approach when working with patients and for the development of interventions to improve patient outcomes by improving medication adherence. We enrolled adults who had diagnosed asthma and who were prescribed daily inhaled corticosteroid medication. We used published and validated instruments to measure medical characteristics including asthma features, practical asthma knowledge and perceived involvement in care and psychological characteristics including anxiety, depression, optimism, and personality traits, to assess the relationship with medication non-adherence. A total of 126 participants provided data, with 64 (50.8%) of the participants identified as non-adherent. Multivariate analyses showed that younger age, high neuroticism scores and a previous asthma hospital admission were associated with non-adherence. Interestingly, depression was associated with a lower risk of non-adherence. This study showed that a personalized medicine approach would include interventions targeting those who are younger, who have been in hospital for asthma and who rate high on the neuroticism personality trait. Given the availability of effective medications for asthma, better understanding of the characteristics associated with non-adherence is important to enhance optimal self-management.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-14
      DOI: 10.3390/jpm10030126
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 127: Radiomic Analysis of MRI Images is Instrumental
           to the Stratification of Ovarian Cysts

    • Authors: Roxana-Adelina Lupean, Paul-Andrei Ștefan, Diana Sorina Feier, Csaba Csutak, Balaji Ganeshan, Andrei Lebovici, Bianca Petresc, Carmen Mihaela Mihu
      First page: 127
      Abstract: The imaging diagnosis of malignant ovarian cysts relies on their morphological features, which are not always specific to malignancy. The histological analysis of these cysts shows specific fluid characteristics, which cannot be assessed by conventional imaging techniques. This study investigates whether the texture-based radiomics analysis (TA) of magnetic resonance (MRI) images of the fluid content within ovarian cysts can function as a noninvasive tool in differentiating between benign and malignant lesions. Twenty-eight patients with benign (n = 15) and malignant (n = 13) ovarian cysts who underwent MRI examinations were retrospectively included. TA of the fluid component was undertaken on an axial T2-weighted sequence. A comparison of resulted parameters between benign and malignant groups was undertaken using univariate, multivariate, multiple regression, and receiver operating characteristics analyses, with the calculation of the area under the curve (AUC). The standard deviation of pixel intensity was identified as an independent predictor of malignant cysts (AUC = 0.738; sensitivity, 61.54%; specificity, 86.67%). The prediction model was able to identify malignant lesions with 84.62% sensitivity and 80% specificity (AUC = 0.841). TA of the fluid contained within the ovarian cysts can differentiate between malignant and benign lesions and potentially act as a noninvasive tool augmenting the imaging diagnosis of ovarian cystic lesions.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-14
      DOI: 10.3390/jpm10030127
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 128: XGBoost Improves Classification of MGMT Promoter
           Methylation Status in IDH1 Wildtype Glioblastoma

    • Authors: Nguyen Quoc Khanh Le, Duyen Thi Do, Fang-Ying Chiu, Edward Kien Yee Yapp, Hui-Yuan Yeh, Cheng-Yu Chen
      First page: 128
      Abstract: Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-15
      DOI: 10.3390/jpm10030128
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 129: Molecular Diagnosis and Novel Therapies for
           Neuromuscular Diseases

    • Authors: Rika Maruyama, Toshifumi Yokota
      First page: 129
      Abstract: With the development of novel targeted therapies, including exon skipping/inclusion and gene replacement therapy, the field of neuromuscular diseases has drastically changed in the last several years. Until 2016, there had been no FDA-approved drugs to treat Duchenne muscular dystrophy (DMD), the most common muscular dystrophy. However, several new personalized therapies, including antisense oligonucleotides eteplirsen for DMD exon 51 skipping and golodirsen and viltolarsen for DMD exon 53 skipping, have been approved in the last 4 years. We are witnessing the start of a therapeutic revolution in neuromuscular diseases. However, the studies also made clear that these therapies are still far from a cure. Personalized genetic medicine for neuromuscular diseases faces several key challenges, including the difficulty of obtaining appropriate cell and animal models and limited its applicability. This Special Issue “Molecular Diagnosis and Novel Therapies for Neuromuscular/Musculoskeletal Diseases” highlights key areas of research progress that improve our understanding and the therapeutic outcomes of neuromuscular diseases in the personalized medicine era.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-16
      DOI: 10.3390/jpm10030129
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 130: Bioinformatics Data Mining Repurposes the JAK2
           (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal
           Adenocarcinoma by Reversing the KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene
           Homolog)-Driven Gene Signature

    • Authors: Li-Wei Liu, Yao-Yu Hsieh, Pei-Ming Yang
      First page: 130
      Abstract: Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive and lethal cancer types due to the late diagnosis, high metastatic potential, and drug resistance. The development of novel therapeutic strategies is urgently needed. KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) is the major driver mutation gene for PDAC tumorigenesis. In this study, we mined cancer genomics data and identified a common KRAS-driven gene signature in PDAC, which is related to cell–cell and cell–extracellular matrix (ECM) interactions. Higher expression of this gene signature was associated with poorer overall survival of PDAC patients. Connectivity Map (CMap) analysis and drug sensitivity profiling predicted that a clinically approved JAK2 (Janus kinase 2)-selective inhibitor, fedratinib (also known as TG-101348), could reverse the KRAS-driven gene signature and exhibit KRAS-dependent anticancer activity in PDAC cells. As an approved treatment for myelofibrosis, the pharmacological and toxicological profiles of fedratinib have been well characterized. It may be repurposed for treating KRAS-driven PDAC in the future.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-16
      DOI: 10.3390/jpm10030130
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 131: Liquid lncRNA Biopsy for the Evaluation of
           Locally Advanced and Metastatic Squamous Cell Carcinomas of the Head and

    • Authors: Izabela Łasińska, Tomasz Kolenda, Kacper Guglas, Magda Kopczyńska, Joanna Sobocińska, Anna Teresiak, Norbert Oksza Strzelecki, Katarzyna Lamperska, Andrzej Mackiewicz, Jacek Mackiewicz
      First page: 131
      Abstract: Background: Long non-coding RNA (lncRNA) are RNA molecules that are more than 200 nucleotides long and have the ability to modify the activity of genes. They can be found in both healthy and cancer tissues, as well as in plasma, saliva and other bodily fluids. They can also be used as biomarkers of early detection, prognosis and chemotherapy resistance in several cancer types. Treatment of head and neck squamous cell carcinoma (HNSCC) patients with locally advanced disease is still difficult, and choice of treatment should be based on more precise and available biomarkers, such as those obtained from a liquid biopsy. For improvement of treatment efficacy, identification and clinical implementation of new biomarkers are of the utmost importance. Methods: Plasma samples drawn before (p1) and three cycles post (p2) (TPF: docetaxel, cisplatin, 5-fluorouracil/PF: cisplatin, 5-fluorouracil) chemotherapy from 53 HNSCC patients (17 with locally advanced and 36 with metastatic disease) and 14 healthy volunteers were studied. Expression levels of 90 lncRNA expression were analyzed using the qRT-PCR method, and the obtained results were compared between proper groups. Statistical analyses were carried out using Jupyter Notebooks (5.7.2), Python (ver. 3.6) and GraphPad Prism 8. Results: The study demonstrated the differences between the expressions of several lncRNA in cancer patients’ and healthy volunteers’ plasma, as well as between locally advanced and metastatic patients’ groups. A correlation between the response to systemic therapy and lncRNA expression levels was observed. Patients with a (high/low) expression of Alpha 250 and Emx2os showed statistically significant differences in progression free survival (PFS), as well as for overall survival (OS) depending on the level of Alpha 250, snaR, SNHG1. The univariate and multivariate Cox regression model showed Alpha 250 as the best prognostic factor for HNSCC patients. Conclusions: Liquid biopsies based on lncRNAs are promising diagnostic tools that can be used to differentiate between those with cancer and healthy individuals. Additionally, they can also serve as biomarkers for chemotherapy resistance. An identified, circulating lncRNA Alpha 250 seems to prove the best prognostic biomarker, associated with extended PFS and OS, and should be validated in a larger cohort in the future.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-16
      DOI: 10.3390/jpm10030131
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 132: Early Prediction of Tumor Response to Neoadjuvant
           Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET
           Parameter for Cancer Stem Cell Metabolism

    • Authors: Chanwoo Kim, Sang-Ah Han, Kyu Yeoun Won, Il Ki Hong, Deog Yoon Kim
      First page: 132
      Abstract: Cancer stem cells (CSCs) contribute to chemoresistance and tumor relapse. By using the distinct metabolic phenotype of CSC, we designed novel PET parameters for CSC metabolism and investigated their clinical values. Patients with breast cancer who underwent 18F-FDG PET/CT before neoadjuvant chemotherapy (NAC) were retrospectively included. We developed a method to measure CSC metabolism using standardized uptake value histogram data. The predictive value of novel CSC metabolic parameters for pathologic complete response (pCR) was assessed with multivariable logistic regression. The association between the CSC parameter and disease-free survival (DFS) was also determined. We identified 82 patients with HER2-positive/triple-negative subtypes and 38 patients with luminal tumors. After multivariable analysis, only metabolic tumor volume for CSC (MTVcsc) among metabolic parameters remained the independent predictor of pCR (OR, 0.12; p = 0.022). MTVcsc successfully predicted pathologic tumor response to NAC in HER2-positive/triple-negative subtypes (accuracy, 74%) but not in the luminal subtype (accuracy, 29%). MTVcsc was also predictive of DFS, with a 3-year DFS of 90% in the lower MTVcsc group (<1.75 cm3) versus 72% in the higher group (>1.75 cm3). A novel data-driven PET parameter for CSC metabolism provides early prediction of pCR after NAC and DFS in HER2-positive and triple-negative subtypes.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-17
      DOI: 10.3390/jpm10030132
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 133: An Exploratory Association Analysis of ABCB1
           rs1045642 and ABCB1 rs4148738 with Non-Major Bleeding Risk in Atrial
           Fibrillation Patients Treated with Dabigatran or Apixaban

    • Authors: Adela-Nicoleta Roşian, Mihaela Iancu, Adrian Pavel Trifa, Ştefan Horia Roşian, Cristina Mada, Cornelia Paula Gocan, Teodora Niţă, Sabina Istratoaie, Paul-Mihai Boarescu, Anca Dana Buzoianu
      First page: 133
      Abstract: (1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-18
      DOI: 10.3390/jpm10030133
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 134: Genomics and Pharmacogenomics Knowledge, Attitude
           and Practice of Pharmacists Working in United Arab Emirates: Findings from
           Focus Group Discussions—A Qualitative Study

    • Authors: Azhar T. Rahma, Iffat Elbarazi, Bassam R. Ali, George P. Patrinos, Luai A. Ahmed, Fatma Al Maskari
      First page: 134
      Abstract: (1) Background: Genomics and pharmacogenomics are relatively new fields in medicine in the United Arab Emirates (UAE). Understanding the knowledge, attitudes and current practices among pharmacists is an important pillar to establish the roadmap for implementing genomic medicine and pharmacogenomics; (2) Methods: A qualitative method was used, with focus group discussions (FGDs) being conducted among pharmacists working in public and private hospitals in Abu Dhabi Emirate. Snowball sampling was used. Thematic inductive analysis was performed by two researchers independently. NVIVO software was used to establish the themes; (3) Results: Lack of knowledge of genomics and pharmacogenomics among pharmacists was one of the most prominent findings. Therefore, the role of pharmacist in making the right decisions was highlighted to be a barrier for pharmacogenomics implementation in the UAE. Pharmacists have a positive attitude toward pharmacogenomics, but they are preoccupied with concern of confidentiality. In addition, religion and culture shadowed their attitudes toward genetic testing; (4) Conclusions: It is highly recommended to introduce new courses and training workshops for healthcare providers to improve the opportunities for genomics and pharmacogenomics application in the UAE. Pharmacists agreed that the health authorities should take the lead for improving trust and confidence in the system for a better future in the era of genomics and pharmacogenomics.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-18
      DOI: 10.3390/jpm10030134
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 135: Is Structured Exercise Performed with
           Supplemental Oxygen a Promising Method of Personalized Medicine in the
           Therapy of Chronic Diseases'

    • Authors: Freitag, Doma, Neunhaeuserer, Cheng, Bloch, Schumann
      First page: 135
      Abstract: Aim: This systematic review aimed to explore the literature to identify in which types of chronic diseases exercise with supplemental oxygen has previously been utilized and whether this type of personalized therapy leads to superior effects in physical fitness and well-being. Methods: Databases (PubMed/MEDLINE, CINHAL, EMBASE, Web of knowledge and Cochrane Library) were searched in accordance with PRISMA. Eligibility criteria included adult patients diagnosed with any type of chronic diseases engaging in supervised exercise training with supplemental oxygen compared to normoxia. A random-effects model was used to pool effect sizes by standardized mean differences (SMD). Results: Out of the identified 4038 studies, 12 articles were eligible. Eleven studies were conducted in chronic obstructive pulmonary disease (COPD), while one study included coronary artery disease (CAD) patients. No statistical differences were observed for markers of physical fitness and patient-reported outcomes on well-being between the two training conditions (SMD −0.10; 95% CI −0.27, 0.08; p = 0.26). Conclusions: We found that chronic exercise with supplemental oxygen has mainly been utilized for COPD patients. Moreover, no superior long-term adaptations on physical fitness, functional capacity or patient-reported well-being were found, questioning the role of this method as a personalized medicine approach. Prospero registration: CRD42018104649
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-19
      DOI: 10.3390/jpm10030135
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 136: Retrospective CT/MRI Texture Analysis of Rapidly
           Progressive Hepatocellular Carcinoma

    • Authors: Charissa Kim, Natasha Cigarroa, Venkateswar Surabhi, Balaji Ganeshan, Anil K. Pillai
      First page: 136
      Abstract: Rapidly progressive hepatocellular carcinoma (RPHCC) is a subset of hepatocellular carcinoma that demonstrates accelerated growth, and the radiographic features of RPHCC versus non-RPHCC have not been determined. The purpose of this retrospective study was to use baseline radiologic features and texture analysis for the accurate detection of RPHCC and subsequent improvement of clinical outcomes. We conducted a qualitative visual analysis and texture analysis, which selectively extracted and enhanced imaging features of different sizes and intensity variation including mean gray-level intensity (mean), standard deviation (SD), entropy, mean of the positive pixels (MPP), skewness, and kurtosis at each spatial scaling factor (SSF) value of RPHCC and non-RPHCC tumors in a computed tomography (CT) cohort of n = 11 RPHCC and n = 11 non-RPHCC and a magnetic resonance imaging (MRI) cohort of n = 13 RPHCC and n = 10 non-RPHCC. There was a statistically significant difference across visual CT irregular margins p = 0.030 and CT texture features in SSF between RPHCC and non-RPHCC for SSF-6, coarse-texture scale, mean p = 0.023, SD p = 0.053, MPP p = 0.023. A composite score of mean SSF-6 binarized + SD SSF-6 binarized + MPP SSF-6 binarized + irregular margins was significantly different between RPHCC and non-RPHCC (p = 0.001). A composite score ≥3 identified RPHCC with a sensitivity of 81.8% and specificity of 81.8% (AUC = 0.884, p = 0.002). CT coarse-texture-scale features in combination with visually detected irregular margins were able to statistically differentiate between RPHCC and non-RPHCC. By developing an image-based, non-invasive diagnostic criterion, we created a composite score that can identify RPHCC patients at their early stages when they are still eligible for transplantation, improving the clinical course of patient care.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-21
      DOI: 10.3390/jpm10030136
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 137: Comprehensive Custom NGS Panel Validation for the
           Improvement of the Stratification of B-Acute Lymphoblastic Leukemia

    • Authors: Adrián Montaño, Jesús Hernández-Sánchez, Maribel Forero-Castro, María Matorra-Miguel, Eva Lumbreras, Cristina Miguel, Sandra Santos, Valentina Ramírez-Maldonado, José Luís Fuster, Natalia de Las Heras, Alfonso García-de Coca, Magdalena Sierra, Julio Dávila, Ignacio de la Fuente, Carmen Olivier, Juan Olazabal, Joaquín Martínez, Nerea Vega-García, Teresa González, Jesús María Hernández-Rivas, Rocío Benito
      First page: 137
      Abstract: Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-21
      DOI: 10.3390/jpm10030137
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 138: Biomarkers for Alzheimer’s Disease (AD) and the
           Application of Precision Medicine

    • Authors: Walter J. Lukiw, Andrea Vergallo, Simone Lista, Harald Hampel, Yuhai Zhao
      First page: 138
      Abstract: An accurate diagnosis of Alzheimer’s disease (AD) currently stands as one of the most difficult and challenging in all of clinical neurology. AD is typically diagnosed using an integrated knowledge and assessment of multiple biomarkers and interrelated factors. These include the patient’s age, gender and lifestyle, medical and genetic history (both clinical- and family-derived), cognitive, physical, behavioral and geriatric assessment, laboratory examination of multiple AD patient biofluids, especially within the systemic circulation (blood serum) and cerebrospinal fluid (CSF), multiple neuroimaging-modalities of the brain’s limbic system and/or retina, followed up in many cases by post-mortem neuropathological examination to finally corroborate the diagnosis. More often than not, prospective AD cases are accompanied by other progressive, age-related dementing neuropathologies including, predominantly, a neurovascular and/or cardiovascular component, multiple-infarct dementia (MID), frontotemporal dementia (FTD) and/or strokes or ‘mini-strokes’ often integrated with other age-related neurological and non-neurological disorders including cardiovascular disease and cancer. Especially over the last 40 years, enormous research efforts have been undertaken to discover, characterize, and quantify more effectual and reliable biological markers for AD, especially during the pre-clinical or prodromal stages of AD so that pre-emptive therapeutic treatment strategies may be initiated. While a wealth of genetic, neurobiological, neurochemical, neuropathological, neuroimaging and other diagnostic information obtainable for a single AD patient can be immense: (i) it is currently challenging to integrate and formulate a definitive diagnosis for AD from this multifaceted and multidimensional information; and (ii) these data are unfortunately not directly comparable with the etiopathological patterns of other AD patients even when carefully matched for age, gender, familial genetics, and drug history. Four decades of AD research have repeatedly indicated that diagnostic profiles for AD are reflective of an extremely heterogeneous neurological disorder. This commentary will illuminate the heterogeneity of biomarkers for AD, comment on emerging investigative approaches and discuss why ‘precision medicine’ is emerging as our best paradigm yet for the most accurate and definitive prediction, diagnosis, and prognosis of this insidious and lethal brain disorder.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-21
      DOI: 10.3390/jpm10030138
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 139: Needs of Families with Children with Cerebral
           Palsy in Latvia and Factors Affecting These Needs

    • Authors: Dace Bertule, Anita Vetra
      First page: 139
      Abstract: In order to provide targeted support to families who are raising children with developmental disorders, it is important to study the family needs and to understand circumstances that may affect them. The aim of this study was to identify the needs of the families with preschool children with cerebral palsy, and study how these needs relate to factors associated with families, children and rehabilitation services. Descriptive analysis showed that families living in Latvia most often need information, social and financial support and coordination of services, and they also need financial support to cover the costs of child care and treatment. The results of the data analysis support the hypothesis that factors characterising families, children with cerebral palsy and rehabilitation services affect the needs of the families with preschool children with cerebral palsy living in Latvia, and the unique impact of these factors depends on the type of needs. Regression analysis revealed that the most important factors affecting the needs of families were related with the socio-economic situation, as well as the support of peers and professionals. The availability and regularity of rehabilitation services, limitations to the child’s functions and health impairments were factors that affected family needs to a lesser extent.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-22
      DOI: 10.3390/jpm10030139
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 140: A Data-Driven Approach to Carrier Screening for
           Common Recessive Diseases

    • Authors: Anna V. Kiseleva, Marina V. Klimushina, Evgeniia A. Sotnikova, Mikhail G. Divashuk, Alexandra I. Ershova, Olga P. Skirko, Olga V. Kurilova, Anastasia A. Zharikova, Eleonora Yu. Khlebus, Irina A. Efimova, Maria S. Pokrovskaya, Petr A. Slominsky, Svetlana A. Shalnova, Alexey N. Meshkov, Oxana M. Drapkina
      First page: 140
      Abstract: Genetic screening is an advanced tool for reducing recessive disease burden. Nowadays, it is still unclear as to the number of genes or their variants that are necessary for effective screening. This paper describes the development of a carrier screening custom panel for cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss consisting of 116 variants in the CFTR, PAH, SERPINA1, and GJB2 genes. The approach is based on the cheapest and fastest method, on using a small number of genes, and on the estimation of the effectiveness of carriers’ detection. The custom panel was tested on a population-based cohort that included 1244 participants. Genotypes were determined by the TaqMan OpenArray Genotyping platform on the QuantStudio 12K Flex Real-Time PCR System. The frequency of heterozygotes in the Russian population was 16.87% or 1:6 (CI95%: 14.76–19.00% by Clopper-Pearson exact method): in CFTR—2.81% (1:36), PAH—2.33% (1:43), SERPINA1—4.90% (1:20), and GJB2—6.83% (1:15). The data on allele frequencies were obtained for the first time on a Russian population. The panel allows us to identify the vast majority of carriers of recessive diseases in the population. It is an effective approach to carrier screening for common recessive diseases.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-09-22
      DOI: 10.3390/jpm10030140
      Issue No: Vol. 10, No. 3 (2020)
  • JPM, Vol. 10, Pages 50: An Omics View of Emery–Dreifuss Muscular

    • Authors: Nicolas Vignier, Antoine Muchir
      First page: 50
      Abstract: Recent progress in Omics technologies has started to empower personalized healthcare development at a thorough biomolecular level. Omics have subsidized medical breakthroughs that have started to enter clinical proceedings. The use of this scientific know-how has surfaced as a way to provide a more far-reaching view of the biological mechanisms behind diseases. This review will focus on the discoveries made using Omics and the utility of these approaches for Emery–Dreifuss muscular dystrophy.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-15
      DOI: 10.3390/jpm10020050
      Issue No: Vol. 10, No. 2 (2020)
  • JPM, Vol. 10, Pages 51: Risk Factors Associated with Low Back Pain among A
           Group of 1510 Pregnant Women

    • Authors: Aleksandra Bryndal, Marian Majchrzycki, Agnieszka Grochulska, Sebastian Glowinski, Agnieszka Seremak-Mrozikiewicz
      First page: 51
      Abstract: Background: Low Back Pain (LBP) is a frequent, very common, and costly health problem. LBP, which occurs during pregnancy, may become a lifelong problem. The aim of this study was to determine the risk factors associated with LBP in pregnant women. Methods: The study included 1510 pregnant women. A questionnaire assessing demography, lifestyle, prevalence, and characteristics was designed and used in the study. Pain intensity was assessed with the VAS (Visual Analogue Scale). The RMDQ (Roland Morris Disability Questionnaire) was used to assess the effect that low back pain had on the functional capacity of a pregnant woman. Middle (thoracic) and low back pain disability was measured with the help of the ODI (Oswestry Disability Index) questionnaire. Results: The study confirmed that lying/sleeping (49.6%) and sitting positions (38.7%) as well as walking (37.2%) are the most significant factors causing LBP. It was also found that women who had not engaged in physical activity were more likely to experience LBP. Conclusions: Predisposing factors for LBP in pregnancy are LBP in previous pregnancies, back pain during menstruation, a younger age and a lack of physical activity. Most women in pregnancy with LBP experienced minimal and mild disability.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-15
      DOI: 10.3390/jpm10020051
      Issue No: Vol. 10, No. 2 (2020)
  • JPM, Vol. 10, Pages 52: Correlation between F18-FDG PET/CT Imaging and
           BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response
           in Papillary Thyroid Cancers

    • Authors: Andra Piciu, Maria-Iulia Larg, Doina Piciu
      First page: 52
      Abstract: In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-19
      DOI: 10.3390/jpm10020052
      Issue No: Vol. 10, No. 2 (2020)
  • JPM, Vol. 10, Pages 53: rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and
           Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving
           Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

    • Authors: Khaled Naja, Ali Salami, Said El Shamieh, Rajaa Fakhoury
      First page: 53
      Abstract: Background and Objective: Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in SLC22A1, CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination therapy in individuals with type 2 diabetes mellitus (T2DM). Methods: Eighty-eight Lebanese individuals with T2DM received metformin/sulfonylurea combination therapy over 3 and 6 months. The clinical and biochemical characteristics were collected. Genotyping of rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 was performed using hybridization probes on real-time polymerase chain reaction (PCR) instrument. Statistical analysis was performed using SPSS 22.0. Results: The levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) showed a statistically significant reduction over 3 and 6 months of follow-up (p < 0.001). An interaction between rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 (p = 0.035) was found associated with reduced levels of HbA1c levels after 3 and 6 months. A significant difference between the means of HbA1c was observed among the different groups after 3 and 6 months (p = 0.004 and p < 0.001, respectively). The most beneficial group was; AA and AC, *1*3, whereas the individuals that benefited the least were CC, *1*3 at 3 and 6 months. In contrast to HbA1c, no interaction was found between the three polymorphisms to affect FBS (p = 0.581). Conclusion: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-20
      DOI: 10.3390/jpm10020053
      Issue No: Vol. 10, No. 2 (2020)
  • JPM, Vol. 10, Pages 54: Implementation of MALDI Mass Spectrometry Imaging
           in Cancer Proteomics Research: Applications and Challenges

    • Authors: Eline Berghmans, Kurt Boonen, Evelyne Maes, Inge Mertens, Patrick Pauwels, Geert Baggerman
      First page: 54
      Abstract: Studying the proteome–the entire set of proteins in cells, tissues, organs and body fluids—is of great relevance in cancer research, as differential forms of proteins are expressed in response to specific intrinsic and extrinsic signals. Discovering protein signatures/pathways responsible for cancer transformation may lead to a better understanding of tumor biology and to a more effective diagnosis, prognosis, recurrence and response to therapy. Moreover, proteins can act as a biomarker or potential drug targets. Hence, it is of major importance to implement proteomic, particularly mass spectrometric, approaches in cancer research, to provide new crucial insights into tumor biology. Recently, mass spectrometry imaging (MSI) approaches were implemented in cancer research, to provide individual molecular characteristics of each individual tumor while retaining molecular spatial distribution, essential in the context of personalized disease management and medicine.
      Citation: Journal of Personalized Medicine
      PubDate: 2020-06-22
      DOI: 10.3390/jpm10020054
      Issue No: Vol. 10, No. 2 (2020)
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