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  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Has knowledge of the vaginal microbiome altered approaches to health and
           disease' [version 1; referees: 4 approved]

    • Authors: Gregor Reid
      Abstract: Sixteen years ago, when we published the first molecular characterization of the vaginal microbiota, little did we know the vast numbers of species that would be detected in this niche. As exciting as these discoveries have been, what have they and more recent advances contributed to how vaginal health and disease are managed' This review provides a brief discussion of the potential, but so far limited, applications that have arisen from microbiome research. Calls for innovation have been made before but to little avail.
      PubDate: 2018-04-13T15:47:18Z
      DOI: 10.12688/f1000research.13706.1
      Issue No: Vol. 7 (2018)
  • Generating and repairing genetically programmed DNA breaks during
           immunoglobulin class switch recombination [version 1; referees: 2

    • Authors: Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
      Abstract: Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity.
      PubDate: 2018-04-13T13:22:39Z
      DOI: 10.12688/f1000research.13247.1
      Issue No: Vol. 7 (2018)
  • Endoplasmic reticulum turnover: ER-phagy and other flavors in selective
           and non-selective ER clearance [version 1; referees: 2 approved]

    • Authors: Ilaria Fregno, Maurizio Molinari
      Abstract: The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells. It is deputed to lipid and protein biosynthesis, calcium storage, and the detoxification of various exogenous and endogenous harmful compounds. ER activity and size must be adapted rapidly to environmental and developmental conditions or biosynthetic demand. This is achieved on induction of thoroughly studied transcriptional/translational programs defined as “unfolded protein responses” that increase the ER volume and the expression of ER-resident proteins regulating the numerous ER functions. Less understood are the lysosomal catabolic processes that maintain ER size at steady state, that prevent excessive ER expansion during ER stresses, or that ensure return to physiologic ER size during recovery from ER stresses. These catabolic processes may also be activated to remove ER subdomains where proteasome-resistant misfolded proteins or damaged lipids have been segregated. Insights into these catabolic mechanisms have only recently emerged with the identification of so-called ER-phagy receptors, which label specific ER subdomains for selective lysosomal delivery for clearance. Here, in eight chapters and one addendum, we comment on recent advances in ER turnover pathways induced by ER stress, nutrient deprivation, misfolded proteins, and live bacteria. We highlight the role of yeast (Atg39 and Atg40) and mammalian (FAM134B, SEC62, RTN3, and CCPG1) ER-phagy receptors and of autophagy genes in selective and non-selective catabolic processes that regulate cellular proteostasis by controlling ER size, turnover, and function.
      PubDate: 2018-04-13T10:58:57Z
      DOI: 10.12688/f1000research.13968.1
      Issue No: Vol. 7 (2018)
  • The acid tolerance response and pH adaptation of Enterococcus faecalis in
           extract of lime Citrus aurantiifolia from Aceh Indonesia [version 2;
           referees: 2 approved]

    • Authors: Zaki Mubarak, Cut Soraya
      Abstract: Background: The objective of the present study was to evaluate the acid tolerance response and pH adaptation when Enterococcus faecalis interacted with extract of lime ( Citrus aurantiifolia). Methods: We used E. faecalis ATCC 29212 and lime extract from Aceh, Indonesia. The microbe was analyzed for its pH adaptation, acid tolerance response, and adhesion assay using a light microscope with a magnification of x1000. Further, statistical tests were performed to analyze both correlation and significance of the acid tolerance and pH adaptation as well as the interaction activity. Results: E. faecalis was able to adapt to a very acidic environment (pH 2.9), which was characterized by an increase in its pH (reaching 4.2) at all concentrations of the lime extract (p < 0.05). E. faecalis was also able to provide acid tolerance response to lime extract based on spectrophotometric data (595 nm) (p < 0.05). Also, the interaction activity of E. faecalis in different concentrations of lime extract was relatively stable within 6 up to 12 hours (p < 0.05), but it became unstable within 24–72 hours (p> 0.05) based on the mass profiles of its interaction activity. Conclusions: E. faecalis can adapt to acidic environments (pH 2.9–4.2); it is also able to tolerate acid generated by Citrus aurantiifolia extract, revealing a stable interaction in the first 6–12 hours.
      PubDate: 2018-04-11T11:15:03Z
      DOI: 10.12688/f1000research.13990.2
      Issue No: Vol. 7 (2018)
  • Recent advances in the understanding and management of underactive bladder
           [version 1; referees: 4 approved]

    • Authors: Su-Min Lee, Hashim Hashim
      Abstract: Underactive bladder (UAB) is an important and complex urological condition resulting from the urodynamic finding of detrusor underactivity. It can manifest in a wide range of lower urinary tract symptoms, from voiding to storage complaints, and can overlap with other conditions, including overactive bladder and bladder outlet obstruction. However, UAB continues to be poorly understood and inadequately researched. In this article, we review the contemporary literature pertaining to recent advances in defining, understanding, and managing UAB.
      PubDate: 2018-04-10T10:11:05Z
      DOI: 10.12688/f1000research.13660.1
      Issue No: Vol. 7 (2018)
  • An overview of gambling disorder: from treatment approaches to risk
           factors [version 1; referees: 2 approved]

    • Authors: José M Menchon, Gemma Mestre-Bach, Trevor Steward, Fernando Fernández-Aranda, Susana Jiménez-Murcia
      Abstract: Gambling disorder (GD) has been reclassified recently into the “Substance-Related and Addictive Disorders” category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), a landmark occurrence for a behavioral addiction. GD is characterized by recurrent, maladaptive gambling behavior that results in clinically significant distress. Although the number of randomized controlled trials assessing the effectiveness of pharmacological treatments is limited, some pharmacological treatments, notably opiate antagonists, have been employed in the treatment of GD. Patients with GD often present cognitive distortions and specific personality traits, making treatment more difficult. Cognitive behavioral therapy has become the most common psychological intervention for treating gambling problems, and it is effective in reducing gambling behavior. In this brief overview, we provide a report on the state of pharmacological and psychological treatments for gambling disorder. Risk factors and potential future lines of research are addressed.
      PubDate: 2018-04-09T09:33:51Z
      DOI: 10.12688/f1000research.12784.1
      Issue No: Vol. 7 (2018)
  • Role of B-cell receptors for B-cell development and antigen-induced
           differentiation [version 1; referees: 2 approved]

    • Authors: Juan Carlos Yam-Puc, Lingling Zhang, Yang Zhang, Kai-Michael Toellner
      Abstract: B-cell development is characterized by a number of tightly regulated selection processes. Signals through the B-cell receptor (BCR) guide and are required for B-cell maturation, survival, and fate decision. Here, we review the role of the BCR during B-cell development, leading to the emergence of B1, marginal zone, and peripheral follicular B cells. Furthermore, we discuss BCR-derived signals on activated B cells that lead to germinal center and plasma cell differentiation.
      PubDate: 2018-04-06T15:24:06Z
      DOI: 10.12688/f1000research.13567.1
      Issue No: Vol. 7 (2018)
  • Spatial band-pass filtering aids decoding musical genres from auditory
           cortex 7T fMRI [version 2; referees: 2 approved]

    • Authors: Ayan Sengupta, Stefan Pollmann, Michael Hanke
      Abstract: Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation – primarily in the visual cortex. Previous research indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we applied an analysis strategy from a previous study on decoding visual orientation from V1 to publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex. The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.
      PubDate: 2018-04-04T09:31:06Z
      DOI: 10.12688/f1000research.13689.2
      Issue No: Vol. 7 (2018)
  • New technology to assess sleep apnea: wearables, smartphones, and
           accessories [version 1; referees: 2 approved]

    • Authors: Thomas Penzel, Christoph Schöbel, Ingo Fietze
      Abstract: Sleep medicine has been an expanding discipline during the last few decades. The prevalence of sleep disorders is increasing, and sleep centers are expanding in hospitals and in the private care environment to meet the demands. Sleep medicine has evidence-based guidelines for the diagnosis and treatment of sleep disorders. However, the number of sleep centers and caregivers in this area is not sufficient. Many new methods for recording sleep and diagnosing sleep disorders have been developed. Many sleep disorders are chronic conditions and require continuous treatment and monitoring of therapy success. Cost-efficient technologies for the initial diagnosis and for follow-up monitoring of treatment are important. It is precisely here that telemedicine technologies can meet the demands of diagnosis and therapy follow-up studies. Wireless recording of sleep and related biosignals allows diagnostic tools and therapy follow-up to be widely and remotely available. Moreover, sleep research requires new technologies to investigate underlying mechanisms in the regulation of sleep in order to better understand the pathophysiology of sleep disorders. Home recording and non-obtrusive recording over extended periods of time with telemedicine methods support this research. Telemedicine allows recording with little subject interference under normal and experimental life conditions.
      PubDate: 2018-03-29T14:56:40Z
      DOI: 10.12688/f1000research.13010.1
      Issue No: Vol. 7 (2018)
  • Recent advances in biologic therapy of asthma and the role in therapy of
           chronic rhinosinusitis [version 1; referees: 2 approved]

    • Authors: Rohit Divekar, Devyani Lal
      Abstract: Great strides have been made in the last five years in understanding the pathology of chronic rhinosinusitis (CRS). CRS is now accepted to be the end-stage manifestation of inflammation resultant from various pathogenetic mechanisms. This has resulted in increasing recognition of distinct CRS endotypes. Such endotypes encompass a cluster of patients with similar pathogenic mechanisms that may have common therapeutic targets and responsiveness to interventions. The elucidation of mechanisms leading to the development of chronic upper (sino-nasal) airway inflammation has to some extent paralleled investigations of aberrant pathways operant in asthma. In this review, we focus on recent developments in understanding the innate immune pathways as well as adaptive (late) immune responses in CRS and asthma and their implication as potentially modifiable targets in CRS. Specific biologic therapy (that is, monoclonal antibodies targeting cytokines, cytokine receptors, or specific key molecules targeting inflammation) is an exciting proposition for the future of medical management of CRS. As of the writing of this article, the agents described are not approved for use in CRS; many have partial approval for use in asthma or are considered experimental.
      PubDate: 2018-03-29T13:51:15Z
      DOI: 10.12688/f1000research.13170.1
      Issue No: Vol. 7 (2018)
  • Recent advances in understanding the biology of marginal zone lymphoma
           [version 1; referees: 2 approved]

    • Authors: Francesco Bertoni, Davide Rossi, Emanuele Zucca
      Abstract: There are three different marginal zone lymphomas (MZLs): the extranodal MZL of mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma), the splenic MZL, and the nodal MZL. The three MZLs share common lesions and deregulated pathways but also present specific alterations that can be used for their differential diagnosis. Although trisomies of chromosomes 3 and 18, deletions at 6q23, deregulation of nuclear factor kappa B, and chromatin remodeling genes are frequent events in all of them, the three MZLs differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel like factor 2 (KLF2) or the receptor-type protein tyrosine phosphatase delta (PTPRD). Since a better understanding of the molecular events underlying each subtype may have practical relevance, this review summarizes the most recent and main advances in our understanding of the genetics and biology of MZLs.
      PubDate: 2018-03-28T08:21:59Z
      DOI: 10.12688/f1000research.13826.1
      Issue No: Vol. 7 (2018)
  • A world without bacterial meningitis: how genomic epidemiology can inform
           vaccination strategy [version 1; referees: 2 approved]

    • Authors: Charlene M.C. Rodrigues, Martin C.J. Maiden
      Abstract: Bacterial meningitis remains an important cause of global morbidity and mortality. Although effective vaccinations exist and are being increasingly used worldwide, bacterial diversity threatens their impact and the ultimate goal of eliminating the disease. Through genomic epidemiology, we can appreciate bacterial population structure and its consequences for transmission dynamics, virulence, antimicrobial resistance, and development of new vaccines. Here, we review what we have learned through genomic epidemiological studies, following the rapid implementation of whole genome sequencing that can help to optimise preventative strategies for bacterial meningitis.
      PubDate: 2018-03-27T14:37:59Z
      DOI: 10.12688/f1000research.13793.1
      Issue No: Vol. 7 (2018)
  • Case Report: Dermoscopic features of oral lichen planus - the evolution of
           mucoscopy [version 2; referees: 2 approved]

    • Authors: Sidharth Sonthalia, Sangeeta Varma, Abhijeet Kumar Jha, Deepak Jakhar, Feroze Kaliyadan
      Abstract: Dermoscopy, a non-invasive technique for cutaneous diagnosis is being increasingly studied in various disorders of the skin, nails and scalp. However, it has been under-utilized for the diagnosis and characterization of mucosal disorders. The dermoscopic characterization of cutaneous lichen planus and its variants has been well documented with Wickham’s striae constituting the hallmark of the condition. However, the dermoscopic features of oral lichen planus with hand-held or videodermoscopy remain to be elucidated. We present the case of a young adult man who presented with asymptomatic white lacy lesions over a bluish-black background over the tongue, patchy hyperpigmentation of the buccal mucosae and gingivae, and longitudinal melanonychia involving some nails. History of intake of any drugs preceding the lesions, smoking, chewing of betel nut and dental implants was negative. Family history was non-contributory. There were no cutaneous lesions suggestive of lichen planus. Mucoscopy (dermoscopy of the mucosa, oral in this case) and onychoscopy were done followed by biopsy from the tongue that confirmed the diagnosis of lichen planus. Oral mucoscopy of the tongue revealed a tri-colored pattern with structureless veil-like grey-white areas (modified Wickham’s striae), well-demarcated red glossy erosions, and violaceous-to-brown clods. Additionally, vascular pattern of dotted and linear to curved vessels along the borders of leukoplakia-like areas and erosions were observed. Onychoscopy confirmed lichen planus-associated melanonychia. Dermoscopy also proved useful in conveniently ruling out other disorders typified by mucosal and nail pigmentation such as Laugier Hunziker syndrome and drug-induced changes. Although direct oral microscopy has been used in defining features of oral lichen planus, to the best of our knowledge this case is the first report on mucoscopy or dermoscopy of oral lichen planus
      PubDate: 2018-03-27T13:20:30Z
      DOI: 10.12688/f1000research.14134.2
      Issue No: Vol. 7 (2018)
  • Epidemiological, behavioural, and clinical factors associated with
           antimicrobial-resistant gonorrhoea: a review [version 1; referees: 2

    • Authors: Million Abraha, Dianne Egli-Gany, Nicola Low
      Abstract: Antimicrobial-resistant Neisseria gonorrhoeae is a global public health problem in the 21st century. N. gonorrhoeae has developed resistance to all classes of antibiotics used for empirical treatment, and clinical treatment failure caused by extensively resistant strains has been reported. Identifying specific factors associated with an increased risk of antimicrobial-resistant N. gonorrhoeae might help to develop strategies to improve antimicrobial stewardship. In this review, we describe the findings of 24 studies, published between 1989 and 2017, that examined epidemiological, behavioural, and clinical factors and their associations with a range of antimicrobial agents used to treat gonorrhoea. Antimicrobial-resistant N. gonorrhoeae is more common in older than younger adults and in men who have sex with men compared with heterosexual men and women. Antimicrobial-resistant N. gonorrhoeae is less common in some black minority and Aboriginal ethnic groups than in the majority white population in high-income countries. The factors associated with antimicrobial-resistant gonorrhoea are not necessarily those associated with a higher risk of gonorrhoea.
      PubDate: 2018-03-27T11:31:17Z
      DOI: 10.12688/f1000research.13600.1
      Issue No: Vol. 7 (2018)
  • Rett syndrome from bench to bedside: recent advances [version 1; referees:
           2 approved]

    • Authors: Yann Ehinger, Valerie Matagne, Laurent Villard, Jean-Christophe Roux
      Abstract: Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Mecp2 is known to play a role in chromatin organization and transcriptional regulation. In this review, we report the latest advances on the molecular function of Mecp2 and the new animal and cellular models developed to better study Rett syndrome. Finally, we present the latest innovative therapeutic approaches, ranging from classical pharmacology to correct symptoms to more innovative approaches intended to cure the pathology.
      PubDate: 2018-03-26T14:59:54Z
      DOI: 10.12688/f1000research.14056.1
      Issue No: Vol. 7 (2018)
  • Hazard and risk assessment strategies for nanoparticle exposures: how far
           have we come in the past 10 years' [version 1; referees: 2 approved]

    • Authors: David B Warheit
      Abstract: Nanotechnology is an emerging, cross-disciplinary technology designed to create and synthesize new materials at the nanoscale (generally defined as a particle size range of ≤10-9 meters) to generate innovative or altered material properties. The particle properties can be modified to promote different and more flexible applications, resulting in consumer benefits, particularly in medical, cosmetic, and industrial applications. As this applied science matures and flourishes, concerns have arisen regarding potential health effects of exposures to untested materials, as many newly developed products have not been adequately evaluated. Indeed, it is necessary to ensure that societal and commercial advantages are not outweighed by potential human health or environmental disadvantages. Therefore, a variety of international planning activities or research efforts have been proposed or implemented, particularly in the European Union and United States, with the expectation that significant advances will be made in understanding potential hazards related to exposures in the occupational and/or consumer environments. One of the first conclusions reached regarding hazardous effects of nanoparticles stemmed from the findings of early pulmonary toxicology studies, suggesting that lung exposures to ultrafine particles were more toxic than those to larger, fine-sized particles of similar chemistry. This review documents some of the conceptual planning efforts, implementation strategies/activities, and research accomplishments over the past 10 years or so. It also highlights (in this author’s opinion) some shortcomings in the research efforts and accomplishments over the same duration. In general, much progress has been made in developing and implementing environmental, health, and safety research-based protocols for addressing nanosafety issues. However, challenges remain in adequately investigating health effects given 1) many different nanomaterial types, 2) various potential routes of exposure, 3) nanomaterial characterization issues, 4) limitations in research methodologies, such as time-course and dose-response issues, and 5) inadequate in vitro methodologies for in vivo standardized, guideline toxicity testing.
      PubDate: 2018-03-26T09:17:20Z
      DOI: 10.12688/f1000research.12691.1
      Issue No: Vol. 7 (2018)
  • Recent advances in cardiac catheterization for congenital heart disease
           [version 1; referees: 2 approved]

    • Authors: Sok-Leng Kang, Lee Benson
      Abstract: The field of pediatric and adult congenital cardiac catheterization has evolved rapidly in recent years. This review will focus on some of the newer endovascular technological and management strategies now being applied in the pediatric interventional laboratory. Emerging imaging techniques such as three-dimensional (3D) rotational angiography, multi-modal image fusion, 3D printing, and holographic imaging have the potential to enhance our understanding of complex congenital heart lesions for diagnostic or interventional purposes. While fluoroscopy and standard angiography remain procedural cornerstones, improved equipment design has allowed for effective radiation exposure reduction strategies. Innovations in device design and implantation techniques have enabled the application of percutaneous therapies in a wider range of patients, especially those with prohibitive surgical risk. For example, there is growing experience in transcatheter duct occlusion in symptomatic low-weight or premature infants and stent implantation into the right ventricular outflow tract or arterial duct in cyanotic neonates with duct-dependent pulmonary circulations. The application of percutaneous pulmonary valve implantation has been extended to a broader patient population with dysfunctional ‘native’ right ventricular outflow tracts and has spurred the development of novel techniques and devices to solve associated anatomic challenges. Finally, hybrid strategies, combining cardiosurgical and interventional approaches, have enhanced our capabilities to provide care for those with the most complex of lesions while optimizing efficacy and safety.
      PubDate: 2018-03-26T07:59:47Z
      DOI: 10.12688/f1000research.13021.1
      Issue No: Vol. 7 (2018)
  • Case Report: Clinically amyopathic dermatomyositis presenting acutely with
           isolated facial edema [version 2; referees: 2 approved]

    • Authors: Efthymia Pappa, Marina Gkeka, Asimina Protogerou, Leonidas Marinos, Chariclia Loupa, Constantinos Christopoulos
      Abstract: A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute, clinically amyopathic dermatomyositis in adults. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules).
      PubDate: 2018-03-26T07:58:02Z
      DOI: 10.12688/f1000research.13604.2
      Issue No: Vol. 7 (2018)
  • Timely referral saves the lives of mothers and newborns: Midwifery led
           continuum of care in marginalized teagarden communities – A qualitative
           case study in Bangladesh [version 1; referees: 1 approved, 2 approved with

    • Authors: Animesh Biswas, Rondi Anderson, Sathyanarayanan Doraiswamy, Abu Sayeed Md. Abdullah, Nabila Purno, Fazlur Rahman, Abdul Halim
      Abstract: Background: Prompt and efficient identification, referral of pregnancy related complications and emergencies are key factors to the reduction of maternal and newborn morbidity and mortality. As a response to this critical need, a midwifery led continuum of reproductive health care was introduced in five teagardens in the Sylhet division, Bangladesh during 2016. Within this intervention, professional midwives provided reproductive healthcare to pregnant teagarden women in the community.  This study evaluates the effect of the referral of pregnancy related complications. Methods: A qualitative case study design by reviewing records retrospectively was used to explore the effect of deploying midwives on referrals of pregnancy related complications from the selected teagardens to the referral health facilities in Moulvibazar district of the Sylhet division during 2016.  In depth analyses was also performed on 15 randomly selected cases to understand the facts behind the referral. Results: Out of a total population of 450 pregnant women identified by the midwives, 72 complicated mothers were referred from the five teagardens to the facilities. 76.4% of mothers were referred to conduct delivery at facilities, and 31.1% of them were referred with the complication of prolonged labour. Other major complications were pre-eclampsia (17.8%), retention of the placenta with post-partum hemorrhage (11.1%) and premature rupture of the membrane (8.9%). About 60% of complicated mothers were referred to the primary health care centre, and among them 14% of mothers were delivered by caesarean section. 94% deliveries resulted in livebirths and only 6% were stillbirths. Conclusions: This study reveals that early detection of pregnancy complications by skilled professionals and timely referral to a facility is beneficial in saving the majority of baby’s as well as mother’s lives in resource-poor teagardens with a considerable access barrier to health facilities.
      PubDate: 2018-03-23T15:18:30Z
      DOI: 10.12688/f1000research.13605.1
      Issue No: Vol. 7 (2018)
  • Case Report: III° atrioventricular block due to fulminant myocarditis
           managed with non-invasive transcutaneous pacing [version 2; referees: 2

    • Authors: Kiran Devkota, Ya Hong Wang, Meng Yi Liu, Yan Li, You Wei Zhang
      Abstract: Fulminant myocarditis is a life-threatening clinical condition. It is the inflammation of myocardium leading to acute heart failure, cardiogenic shock and cardiac arrhythmias. Incidence of fulminant myocarditis is low and mortality is high. Most grievous complications of fulminant myocarditis is mainly cardiac arrhythmias; if there is delay on active management of the patient, it may be fatal. Here, we describe a case of III° atrioventricular block due to fulminant myocarditis that was managed with non-invasive transcutaneous cardiac pacing in the absence of ECMO. The non-invasive transcutaneous pacemaker is a safe, effective and convenient device to revert arrhythmias.
      PubDate: 2018-03-23T14:58:01Z
      DOI: 10.12688/f1000research.14000.2
      Issue No: Vol. 7 (2018)
  • A biochemical logarithmic sensor with broad dynamic range [version 2;
           referees: 2 approved]

    • Authors: Steven A. Frank
      Abstract: Sensory perception often scales logarithmically with the input level. Similarly, the output response of biochemical systems sometimes scales logarithmically with the input signal that drives the system. How biochemical systems achieve logarithmic sensing remains an open puzzle. This article shows how a biochemical logarithmic sensor can be constructed from the most basic principles of chemical reactions. Assuming that reactions follow the classic Michaelis-Menten kinetics of mass action or the more generalized and commonly observed Hill equation response, the summed output of several simple reactions with different sensitivities to the input will often give an aggregate output response that logarithmically transforms the input. The logarithmic response is robust to stochastic fluctuations in parameter values. This model emphasizes the simplicity and robustness by which aggregate chemical circuits composed of sloppy components can achieve precise response characteristics. Both natural and synthetic designs gain from the power of this aggregate approach.
      PubDate: 2018-03-23T14:42:05Z
      DOI: 10.12688/f1000research.14016.2
      Issue No: Vol. 7 (2018)
  • New perspectives in the treatment of body dysmorphic disorder [version 1;
           referees: 2 approved]

    • Authors: Kevin Hong, Vera Nezgovorova, Eric Hollander
      Abstract: Body dysmorphic disorder (BDD) is a disabling illness with a high worldwide prevalence. Patients demonstrate a debilitating preoccupation with one or more perceived defects, often marked by poor insight or delusional convictions. Multiple studies have suggested that selective serotonin reuptake inhibitors and various cognitive behavioral therapy modalities are effective first-line treatments in decreasing BDD severity, relieving depressive symptoms, restoring insight, and increasing quality of life. Selective serotonin reuptake inhibitors have also recently been shown to be effective for relapse prevention. This review provides a comprehensive summary of the current understanding of BDD, including its clinical features, epidemiology, genetics, and current treatment modalities. Additional research is needed to fully elucidate the relationship between BDD and comorbid illnesses such as obsessive–compulsive-related disorders and depression and to develop therapies for refractory patients and those who have contraindications for pharmacological intervention.
      PubDate: 2018-03-23T11:40:28Z
      DOI: 10.12688/f1000research.13700.1
      Issue No: Vol. 7 (2018)
  • Recent advances in managing tricuspid regurgitation [version 1; referees:
           3 approved]

    • Authors: Benedetto Del Forno, Elisabetta Lapenna, Malcom Dalrymple-Hay, Maurizio Taramasso, Alessandro Castiglioni, Ottavio Alfieri, Michele De Bonis
      Abstract: Isolated tricuspid valve surgery is usually carried out with very high morbidity and mortality given the complexity of the affected patients. In light of this, trans-catheter tricuspid valve interventions have been emerging as an attractive alternative to surgery over the last few years. Although feasibility has been shown with a number of devices, clinical experience remains preliminary and associated with significant clinical and technical challenges. Here we describe currently available trans-catheter treatment options for severe tricuspid regurgitation implanted in different locations.
      PubDate: 2018-03-22T08:56:08Z
      DOI: 10.12688/f1000research.13328.1
      Issue No: Vol. 7 (2018)
  • The physiological functions of central nervous system pericytes and a
           potential role in pain [version 1; referees: 2 approved]

    • Authors: Nicholas Beazley-Long, Alexandra M Durrant, Matthew N Swift, Lucy F Donaldson
      Abstract: Central nervous system (CNS) pericytes regulate critical functions of the neurovascular unit in health and disease. CNS pericytes are an attractive pharmacological target for their position within the neurovasculature and for their role in neuroinflammation. Whether the function of CNS pericytes also affects pain states and nociceptive mechanisms is currently not understood. Could it be that pericytes hold the key to pain associated with CNS blood vessel dysfunction' This article reviews recent findings on the important physiological functions of CNS pericytes and highlights how these neurovascular functions could be linked to pain states.
      PubDate: 2018-03-20T14:31:47Z
      DOI: 10.12688/f1000research.13548.1
      Issue No: Vol. 7 (2018)
  • Preliminary investigation of deoxyoligonucleotide binding to ribonuclease
           A using mass spectrometry: An attempt to develop a lab experience for
           undergraduates [version 1; referees: 2 approved]

    • Authors: Daniel D. Clark
      Abstract: Deoxyoligonucleotide binding to bovine pancreatic ribonuclease A (RNase A) was investigated using electrospray ionization ion-trap mass spectrometry (ESI-IT-MS). Deoxyoligonucleotides included CCCCC (dC5) and CCACC (dC2AC2).  This work was an attempt to develop a biochemistry lab experience that would introduce undergraduates to the use of mass spectrometry for the analysis of protein-ligand interactions.  Titration experiments were performed using a fixed RNase A concentration and variable deoxyoligonucleotide concentrations.  Samples at equilibrium were infused directly into the mass spectrometer under native conditions.  For each deoxyoligonucleotide, mass spectra showed one-to-one binding stoichiometry, with marked increases in the total ion abundance of ligand-bound RNase A complexes as a function of concentration, but the accurate determination of dC5 and dC2AC2 dissociation constants was problematic.
      PubDate: 2018-03-20T14:29:11Z
      DOI: 10.12688/f1000research.14268.1
      Issue No: Vol. 7 (2018)
  • Cluster headache: new targets and options for treatment [version 1;
           referees: 2 approved]

    • Authors: Patty Doesborg, Joost Haan
      Abstract: Cluster headache is a severe headache disorder with considerable impact on quality of life. The pathophysiology of the disease remains poorly understood. With few specific targets for treatment, current guidelines mainly include off-label treatment with medication. However, new targets for possible treatment options are emerging. Calcitonin gene-related peptide (CGRP)-targeted medication could become the first (cluster) headache-specific treatment option. Other exciting new treatment options include invasive and non-invasive neuromodulation techniques. Here, we provide a short overview of new targets and treatment options that are being investigated for cluster headache.
      PubDate: 2018-03-20T11:26:38Z
      DOI: 10.12688/f1000research.13380.1
      Issue No: Vol. 7 (2018)
  • Recent advances in understanding West Nile virus host immunity and viral
           pathogenesis [version 1; referees: 2 approved]

    • Authors: Huanle Luo, Tian Wang
      Abstract: West Nile virus (WNV), a mosquito-borne flavivirus, has been a significant public health concern in the United States for nearly two decades. The virus has been linked to acute viral encephalitis, neurological sequelae, and chronic kidney diseases. Neither antiviral drugs nor vaccines are currently available for humans. In vitro cell culture and experimental animal models have been used to study WNV infection in humans. In this review, we will focus on recent findings and provide new insights into WNV host immunity and viral pathogenesis.
      PubDate: 2018-03-19T15:20:34Z
      DOI: 10.12688/f1000research.13362.1
      Issue No: Vol. 7 (2018)
  • Classic and recent advances in understanding amnesia [version 1; referees:
           2 approved]

    • Authors: Richard J. Allen
      Abstract: Neurological amnesia has been and remains the focus of intense study, motivated by the drive to understand typical and atypical memory function and the underlying brain basis that is involved. There is now a consensus that amnesia associated with hippocampal (and, in many cases, broader medial temporal lobe) damage results in deficits in episodic memory, delayed recall, and recollective experience. However, debate continues regarding the patterns of preservation and impairment across a range of abilities, including semantic memory and learning, delayed recognition, working memory, and imagination. This brief review highlights some of the influential and recent advances in these debates and what they may tell us about the amnesic condition and hippocampal function.
      PubDate: 2018-03-16T11:43:00Z
      DOI: 10.12688/f1000research.13737.1
      Issue No: Vol. 7 (2018)
  • Evaluating disparities in the U.S. technology transfer ecosystem to
           improve bench to business translation [version 1; referees: 3 approved, 1
           approved with reservations]

    • Authors: James Weis, Ashvin Bashyam, Gregory J. Ekchian, Kathryn Paisner, Nathan L. Vanderford
      Abstract: Background: A large number of highly impactful technologies originated from academic research, and the transfer of inventions from academic institutions to private industry is a major driver of economic growth, and a catalyst for further discovery. However, there are significant inefficiencies in academic technology transfer. In this work, we conducted a data-driven assessment of translational activity across United States (U.S.) institutions to better understand how effective universities are in facilitating the transfer of new technologies into the marketplace. From this analysis, we provide recommendations to guide technology transfer policy making at both the university and national level. Methods: Using data from the Association of University Technology Managers U.S. Licensing Activity Survey, we defined a commercialization pipeline that reflects the typical path intellectual property takes; from initial research funding to startup formation and gross income. We use this pipeline to quantify the performance of academic institutions at each step of the process, as well as overall, and identify the top performing institutions via mean reciprocal rank. The corresponding distributions were visualized and disparities quantified using the Gini coefficient. Results: We found significant discrepancies in commercialization activity between institutions; a small number of institutions contribute to the vast majority of total commercialization activity. By examining select top performing institutions, we suggest improvements universities and technology transfer offices could implement to emulate the environment at these high-performing institutions. Conclusion: Significant disparities in technology transfer performance exist in which a select set of institutions produce a majority share of the total technology transfer activity. This disparity points to missed commercialization opportunities, and thus, further investigation into the distribution of technology transfer effectiveness across institutions and studies of policy changes that would improve the effectiveness of the commercialization pipeline is warranted.
      PubDate: 2018-03-15T15:52:31Z
      DOI: 10.12688/f1000research.14210.1
      Issue No: Vol. 7 (2018)
  • The role of tumor microenvironment in resistance to anti-angiogenic
           therapy [version 1; referees: 2 approved]

    • Authors: Shaolin Ma, Sunila Pradeep, Wei Hu, Dikai Zhang, Robert Coleman, Anil Sood
      Abstract: Anti-angiogenic therapy has been demonstrated to increase progression-free survival in patients with many different solid cancers. Unfortunately, the benefit in overall survival is modest and the rapid emergence of drug resistance is a significant clinical problem. Over the last decade, several mechanisms have been identified to decipher the emergence of resistance. There is a multitude of changes within the tumor microenvironment (TME) in response to anti-angiogenic therapy that offers new therapeutic opportunities. In this review, we compile results from contemporary studies related to adaptive changes in the TME in the development of resistance to anti-angiogenic therapy. These include preclinical models of emerging resistance, dynamic changes in hypoxia signaling and stromal cells during treatment, and novel strategies to overcome resistance by targeting the TME.
      PubDate: 2018-03-15T13:49:06Z
      DOI: 10.12688/f1000research.11771.1
      Issue No: Vol. 7 (2018)
  • Repeated sessions of bilateral transcranial direct current stimulation on
           intractable tinnitus: a study protocol for a double-blind randomized
           controlled trial [version 1; referees: 2 approved]

    • Authors: Arash Bayat, Miguel Mayo, Samaneh Rashidi, Nader Saki, Ali Yadollahpour
      Abstract: Background: Transcranial Direct Current Stimulation (tDCS) is reportedly a potential treatment option for chronic tinnitus. The main drawbacks of previous studies are short term follow up and focusing on the efficacy of single session tDCS. This study aims to investigate the therapeutic efficacy, adverse effects (AEs) and tolerability of repeated sessions of bilateral tDCS over auditory cortex (AC) on tinnitus symptoms Methods: This will be a double-blinded randomized placebo controlled parallel trial on patients (n=90) with intractable chronic tinnitus (> 2 years) randomly divided into three groups of anodal, cathodal, and sham tDCS. In the sham treatment, after 30 sec the device will be turned OFF without informing the patients. The tDCS protocol consists of 10 sessions (daily  20 min session; 2 mA current for 5 consecutive days per week and 2 consecutive weeks) applied through 35 cm2 electrodes. The primary outcome is tinnitus handicap inventory (THI) which will be assessed pre- and post-intervention and at one month follow-up. The secondary outcomes are tinnitus loudness and distress to be assessed using a visual analogue scale (VAS) pre-intervention, and immediately, one hour, one week, and one month after last stimulation. The AEs and tolerability of patients will be evaluated after each session using a customized questionnaire. Possible interactions between the disease features and treatment response will be evaluated.   Discussion: To our knowledge this is the first study to investigate the effects of repeated sessions of tDCS on chronic tinnitus symptoms with one month follow-up. In addition, the AEs, and tolerability of patients will be studied. In addition, the possible interactions between the disease specific features including the hearing loss, laterality, type of tinnitus, and treatment response will be evaluated.   Trial registration: The study has been registered as a clinical trial in Iranian Registry of Clinical Trial (IRCT2016110124635N6) on the 01/06/2017.
      PubDate: 2018-03-14T09:00:48Z
      DOI: 10.12688/f1000research.13558.1
      Issue No: Vol. 7 (2018)
  • Immune regulation by Tim-3 [version 1; referees: 2 approved]

    • Authors: Hridesh Banerjee, Lawrence P. Kane
      Abstract: T-cell immunoglobulin and mucin domain 3 (Tim-3) is a transmembrane protein that in both mice and humans has been shown to possess various functions in a context-dependent manner. Thus, Tim-3 has been associated with both inhibitory and co-stimulatory function, depending in part on the specific cell type and immune response course. Though originally described on T cells, Tim-3 is now known to be expressed by both lymphoid and non-lymphoid cells within the immune system and even by non-immune cells. In addition, though widely thought of as a negative regulator of immunity, Tim-3 has been shown in more recent studies to have a positive function on both myeloid and lymphoid cells, including T cells. Tim-3 is often expressed at a high level on exhausted T cells in tumors and chronic infection and may engage in crosstalk with other so-called “checkpoint” molecules such as PD-1. Thus, Tim-3 has emerged as a possible therapeutic target, which is being actively explored both pre-clinically and clinically. However, recent research suggests a more complex in vivo role for this protein, compared with other targets in this area.
      PubDate: 2018-03-14T08:56:13Z
      DOI: 10.12688/f1000research.13446.1
      Issue No: Vol. 7 (2018)
  • Using electronic biology based platform to predict flu vaccine efficacy
           for 2018/2019 [version 1; referees: 2 approved, 1 not approved]

    • Authors: Slobodan Paessler, Veljko Veljkovic
      Abstract: Flu epidemics and potential pandemics pose great challenges to public health institutions, scientists and vaccine producers. Creating right vaccine composition for different parts of the world is not trivial and has been historically very problematic. This often resulted in decrease in vaccinations and reduced trust in public health officials. To improve future protection of population against flu we urgently need new methods for vaccine efficacy prediction and vaccine virus selection.
      PubDate: 2018-03-08T16:01:06Z
      DOI: 10.12688/f1000research.14140.1
      Issue No: Vol. 7 (2018)
  • A draft genome sequence for the Ixodes scapularis cell line, ISE6 [version
           1; referees: 2 approved]

    • Authors: Jason R. Miller, Sergey Koren, Kari A. Dilley, Derek M. Harkins, Timothy B. Stockwell, Reed S. Shabman, Granger G. Sutton
      Abstract: Background: The tick cell line ISE6, derived from Ixodes scapularis, is commonly used for amplification and detection of arboviruses in environmental or clinical samples. Methods: To assist with sequence-based assays, we sequenced the ISE6 genome with single-molecule, long-read technology. Results: The draft assembly appears near complete based on gene content analysis, though it appears to lack some instances of repeats in this highly repetitive genome. The assembly appears to have separated the haplotypes at many loci. DNA short read pairs, used for validation only, mapped to the cell line assembly at a higher rate than they mapped to the Ixodes scapularis reference genome sequence. Conclusions: The assembly could be useful for filtering host genome sequence from sequence data obtained from cells infected with pathogens.
      PubDate: 2018-03-08T15:45:54Z
      DOI: 10.12688/f1000research.13635.1
      Issue No: Vol. 7 (2018)
  • The effect of a health literacy approach to counselling on the lifestyle
           of women with gestational diabetes: A clinical trial [version 1; referees:
           3 approved]

    • Authors: Mehrafza Gharachourlo, Zohreh Mahmoodi, Mahnaz Akbari Kamrani, Maryam Tehranizadeh, Kourosh Kabir
      Abstract: Background: Gestational diabetes is a common pregnancy disorder that affects the mother’s and neonate’s health. The present study was conducted to investigate the effect of a health literacy approach to counselling on the lifestyle of women with gestational diabetes. The present randomized controlled clinical trial was conducted in 2017 using a parallel design. The subjects included 84 eligible women presenting to Alborz and Kamali Hospitals, Karaj, Iran. Methods: Convenience sampling was first used to select the subjects. They were then assigned to an intervention or control group based on randomized blocks of four. Both groups attended counselling sessions. The mothers in the intervention group attended six sessions of counselling with a health literacy approach in addition to counselling on routine pregnancy care. The control group attended counselling sessions on safe pregnancy care and received a training package containing all the subjects discussed in the intervention group. The Lifestyle Questionnaire and the Iranian Health Literacy Questionnaire were completed by the mothers at the beginning and at the end of the sessions as well as three weeks after the sessions. The data obtained were analyzed in SPSS-19. Results: According to the study findings, the scores of lifestyle (P=0.8) and health literacy (P=0.423) showed no significant differences between the intervention and control groups before the intervention. Significant differences were, however, observed in the mean scores of lifestyle and health literacy between the two groups immediately and three weeks after the intervention. Comparing the means showed a higher increase in the mean scores in the intervention group (P
      PubDate: 2018-03-06T15:59:14Z
      DOI: 10.12688/f1000research.13838.1
      Issue No: Vol. 7 (2018)
  • Taxa: An R package implementing data standards and methods for taxonomic
           data [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Zachary S.L. Foster, Scott Chamberlain, Niklaus J. Grünwald
      Abstract: The taxa R package provides a set of tools for defining and manipulating taxonomic data. The recent and widespread application of DNA sequencing to community composition studies is making large data sets with taxonomic information commonplace. However, compared to typical tabular data, this information is encoded in many different ways and the hierarchical nature of taxonomic classifications makes it difficult to work with. There are many R packages that use taxonomic data to varying degrees but there is currently no cross-package standard for how this information is encoded and manipulated. We developed the R package taxa to provide a robust and flexible solution to storing and manipulating taxonomic data in R and any application-specific information associated with it. Taxa provides parsers that can read common sources of taxonomic information (taxon IDs, sequence IDs, taxon names, and classifications) from nearly any format while preserving associated data. Once parsed, the taxonomic data and any associated data can be manipulated using a cohesive set of functions modeled after the popular R package dplyr. These functions take into account the hierarchical nature of taxa and can modify the taxonomy or associated data in such a way that both are kept in sync. Taxa is currently being used by the metacoder and taxize packages, which provide broadly useful functionality that we hope will speed adoption by users and developers.
      PubDate: 2018-03-05T14:54:25Z
      DOI: 10.12688/f1000research.14013.1
      Issue No: Vol. 7 (2018)
  • Gene Unprediction with Spurio: A tool to identify spurious protein
           sequences [version 1; referees: 2 approved]

    • Authors: Wolfram Höps, Matt Jeffryes, Alex Bateman
      Abstract: We now have access to the sequences of tens of millions of proteins. These protein sequences are essential for modern molecular biology and computational biology. The vast majority of protein sequences are derived from gene prediction tools and have no experimental supporting evidence for their translation.  Despite the increasing accuracy of gene prediction tools there likely exists a large number of spurious protein predictions in the sequence databases.  We have developed the Spurio tool to help identify spurious protein predictions in prokaryotes.  Spurio searches the query protein sequence against a prokaryotic nucleotide database using tblastn and identifies homologous sequences. The tblastn matches are used to score the query sequence’s likelihood of being a spurious protein prediction using a Gaussian process model. The most informative feature is the appearance of stop codons within the presumed translation of homologous DNA sequences. Benchmarking shows that the Spurio tool is able to distinguish spurious from true proteins. However, transposon proteins are prone to be predicted as spurious because of the frequency of degraded homologs found in the DNA sequence databases. Our initial experiments suggest that less than 1% of the proteins in the UniProtKB sequence database are likely to be spurious and that Spurio is able to identify over 60 times more spurious proteins than the AntiFam resource. The Spurio software and source code is available under an MIT license at the following URL:
      PubDate: 2018-03-02T17:29:46Z
      DOI: 10.12688/f1000research.14050.1
      Issue No: Vol. 7 (2018)
  • Comparing organic versus conventional soil management on soil respiration
           [version 1; referees: 2 approved]

    • Authors: Bence Mátyás, Maritza Elizabeth Chiluisa Andrade, Nora Carmen Yandun Chida, Carina Maribel Taipe Velasco, Denisse Estefania Gavilanes Morales, Gisella Nicole Miño Montero, Lenin Javier Ramirez Cando, Ronnie Xavier Lizano Acevedo
      Abstract: Soil management has great potential to affect soil respiration. In this study, we investigated the effects of organic versus conventional soil management on soil respiration.  We measured the main soil physical-chemical properties from conventional and organic managed soil in Ecuador. Soil respiration was determined using alkaline absorption according to Witkamp.  Soil properties such as organic matter, nitrogen, and humidity, were comparable between conventional and organic soils in the present study, and in a further analysis there was no statically significant correlation with soil respiration. Therefore, even though organic farmers tend to apply more organic material to their fields, but this did not result in a significantly higher CO2 production in their soils in the present study.
      PubDate: 2018-03-02T11:44:18Z
      DOI: 10.12688/f1000research.13852.1
      Issue No: Vol. 7 (2018)
  • Evaluation of portal pressure by doppler ultrasound in patients with
           cirrhosis before and after simvastatin administration – a randomized
           controlled trial [version 1; referees: 1 approved, 2 approved with

    • Authors: Nadia Elwan, Raafat Salah, Manal Hamisa, Ebtsam Shady, Nehad Hawash, Sherief Abd-Elsalam
      Abstract: Background: Portal hypertension is one of the most frequent complications of cirrhosis. β-adrenergic blockers, with or without organic nitrates, are currently used as hypotensive agents. Statins such as simvastatin seem to be safe for patients with chronic liver diseases and exert multiple pleiotropic actions. This study aimed to assess PTH using Doppler ultrasound in patients with cirrhosis before and after simvastatin administration. Methods: This randomized controlled clinical trial was conducted on 40 patients with cirrhosis who were randomized into 2 groups: group I included 20 patients with cirrhosis who were administered 20 mg of simvastatin daily for 2 weeks and then 40 mg daily for another 2 weeks, and group II included 20 patients with cirrhosis who did not receive simvastatin as a control group. All patients underwent full clinical examination, laboratory investigations, and abdominal Doppler ultrasound at baseline and after 30 days to evaluate portal vein diameter, blood flow volume, direction and velocity of portal vein blood flow, hepatic artery resistance and pulsatility indices, splenic artery resistance index, portal hypertension index (PHI), liver vascular index, and modified liver vascular index (MLVI). Results: There was a highly significant decrease in the hepatic artery resistance index  in group I, from 0.785 ± 0.088 to 0.717 ± 0.086 (P < 0.001). There was a significant decrease in the PHI in group I , from 3.915 ± 0.973 m/sec to 3.605 ± 1.168 m/sec (P = 0.024). Additionally, there was a significant increase in the MLVI in group I from 11.540 ± 3.266 cm/sec to 13.305 ± 3.222 cm/sec, an increase of 15.3% from baseline (P = 0.009). No significant adverse effects were detected. Conclusions: Simvastatin is safe and effective in lowering portal hypertension. [ Identifier: NCT02994485]
      PubDate: 2018-03-01T15:29:11Z
      DOI: 10.12688/f1000research.13915.1
      Issue No: Vol. 7 (2018)
  • Alternative miRNAs' Human sequences misidentified as plant miRNAs in
           plant studies and in human plasma [version 1; referees: 2 approved]

    • Authors: Kenneth W. Witwer
      Abstract: Background: A 2017 study reported that “Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi”. Analysis of two human blood plasma sequencing datasets was said to provide evidence for uptake of plant miRNAs into human plasma. The results were also purportedly inconsistent with contamination. Methods: Sequences from public datasets and miRNA databases were compared with results downloaded from the website of the reporting journal. Results: Only one putative plant miRNA (“peu-MIR2910) mapped consistently above background, and this sequence is found with 100% identity in a human rRNA. Several other rarer but consistently mapped putative plant miRNAs also have 100% or near 100% matches to human transcripts or genomic sequences, and some do not appear to map to plant genomes at all. Conclusions: Reanalysis of public data suggests that dietary plant xenomiR uptake is not supported, but instead confirms previous findings that detection of rare plant miRNAs in mammalian sequencing datasets is artifactual. Some putative plant miRNAs, including MIR2910 and MIR2911, may represent human sequence contamination or other artifacts in plant studies, emphasizing the need for rigorous controls and data filtering strategies when assessing possible xenomiRNAs.
      PubDate: 2018-02-28T16:59:26Z
      DOI: 10.12688/f1000research.14060.1
      Issue No: Vol. 7 (2018)
  • Epigenetic silencing of lncRNA MORT in 16 TCGA cancer types [version 1;
           referees: 3 approved]

    • Authors: Lukas Vrba, Bernard W. Futscher
      Abstract: We have previously described a hominid-specific long non-coding RNA, MORT (also known as ZNF667-AS1, Gene ID: 100128252), which is expressed in all normal cell types, but epigenetically silenced during cancer-associated immortalization of human mammary epithelial cells.  Initial analysis of The Cancer Genome Atlas (TCGA) showed that 15 of 17 cancer types, which represent the 10 most common cancers in women and men, display DNA methylation associated MORT silencing in a large fraction of their tumors.  In this study we analyzed MORT expression and DNA methylation state in the remaining 16 TCGA cancer types not previously reported.  Seven of the 16 cancer types showed DNA methylation linked MORT silencing in a large fraction of their tumors.  These are carcinomas (cervical cancer, and cancers of esophagus, stomach, and bile duct), and the non-epithelial tumors mesothelioma, sarcoma, and uterine carcinosarcoma.  Together with the findings from our previous report, MORT expression is silenced by aberrant DNA methylation in 22 of 33 of TCGA cancer types.  These 22 cancers include most carcinoma types, blood derived cancers and sarcomas.  In conclusion, results suggest that the MORT gene is one of the most common epigenetic aberrations seen in human cancer.  Coupled with the timing of MORT gene silencing during in vitro epithelial cell immortalization and its occurrence early in the temporal arc of human carcinogenesis, this provides strong circumstantial evidence for a tumor suppressor role for MORT.
      PubDate: 2018-02-21T09:20:30Z
      DOI: 10.12688/f1000research.13944.1
      Issue No: Vol. 7 (2018)
  • Extended pharmacological miosis is superfluous after glaucoma angle
           surgery: A retrospective study [version 1; referees: 2 approved]

    • Authors: Hamed Esfandiari, Kiana Hassanpour, Mehdi Yaseri, Nils A. Loewen
      Abstract: Background: Pilocarpine is commonly used after angle surgery for glaucoma despite a host of side effects and risks. We hypothesized that a pharmacological miosis during the first two months does not improve short- and long-term results of trabectome-mediated ab interno trabeculectomy. Methods: In this retrospective comparative 1-year case series, we compared 187 trabectome surgery eyes with (P+) or without (P-) 1% pilocarpine for two months. Primary outcome measures were the surgical success defined as intraocular pressure (IOP) ≤ 21 mmHg and decreased ≥ 20%, and no secondary glaucoma surgery. Secondary outcome measures were the number of glaucoma medications, complications, and IOP. Results: We categorized 86 (46%) eyes as P- and 101 (54%) eyes as P+. The mean age was 69.8±10.1 in P- and 70.5±9.4 in P+ (P=0.617) with equal gender distribution (P=0.38). The cumulative probability of qualified success at 12 months was 78.1% in the P- and 81% in the P+ (P=0.35). The IOP was decreased significantly from 20.2±6.8 mmHg at baseline to 15.0±4.8 mmHg at 12 months follow-up in P- (P=0.001) and 18.8±5.3 and 14.7±4.0, respectively (P=0.001). The medications decreased significantly from 1.4±1.2 in P- and 1.4±1.2 in P+ at baseline to 1.0±1.2 and 0.7±1.0, respectively (P=0.183). P- and P+ did not differ in IOP or medications (all P>0.05). In Multivariate Cox Regression models, the baseline IOP and central corneal thickness were associated with failure. Conclusions: Use of postoperative pilocarpine does not improve the efficacy of trabectome surgery.
      PubDate: 2018-02-12T15:49:48Z
      DOI: 10.12688/f1000research.13756.1
      Issue No: Vol. 7 (2018)
  • Matchmaking in Bioinformatics [version 1; referees: 2 approved]

    • Authors: Ewy Mathé, Ben Busby, Helen Piontkivska, Team of Developers
      Abstract: Ever return from a meeting feeling elated by all those exciting talks, yet unsure how all those presented glamorous and/or exciting tools can be useful in your research'  Or do you have a great piece of software you want to share, yet only a handful of people visited your poster' We have all been there, and that is why we organized the Matchmaking for Computational and Experimental Biologists Session at the latest ISCB/GLBIO’2017 meeting in Chicago (May 15-17, 2017). The session exemplifies a novel approach, mimicking “matchmaking”, to encouraging communication, making connections and fostering collaborations between computational and non-computational biologists. More specifically, the session facilitates face-to-face communication between researchers with similar or differing research interests, which we feel are critical for promoting productive discussions and collaborations.  To accomplish this, three short scheduled talks were delivered, focusing on RNA-seq, integration of clinical and genomic data, and chromatin accessibility analyses.  Next, small-table developer-led discussions, modeled after speed-dating, enabled each developer (including the speakers) to introduce a specific tool and to engage potential users or other developers around the table.  Notably, we asked the audience whether any other tool developers would want to showcase their tool and we thus added four developers as moderators of these small-table discussions.  Given the positive feedback from the tool developers, we feel that this type of session is an effective approach for promoting valuable scientific discussion, and is particularly helpful in the context of conferences where the number of participants and activities could hamper such interactions.
      PubDate: 2018-02-09T14:43:12Z
      DOI: 10.12688/f1000research.13705.1
      Issue No: Vol. 7 (2018)
  • Classification of processes involved in sharing individual participant
           data from clinical trials [version 1; referees: 1 approved, 2 approved
           with reservations]

    • Authors: Christian Ohmann, Steve Canham, Rita Banzi, Wolfgang Kuchinke, Serena Battaglia
      Abstract: Background: In recent years, a cultural change in the handling of data from research has resulted in the strong promotion of a culture of openness and increased sharing of data. In the area of clinical trials, sharing of individual participant data involves a complex set of processes and the interaction of many actors and actions. Individual services/tools to support data sharing are available, but what is missing is a detailed, structured and comprehensive list of processes/subprocesses involved and tools/services needed. Methods: Principles and recommendations from a published data sharing consensus document are analysed in detail by a small expert group. Processes/subprocesses involved in data sharing are identified and linked to actors and possible services/tools. Definitions are adapted from the business process model and notation (BPMN) and applied in the analysis. Results: A detailed and comprehensive list of individual processes/subprocesses involved in data sharing, structured according to 9 main processes, is provided. Possible tools/services to support these processes/subprocesses are identified and grouped according to major type of support. Conclusions: The list of individual processes/subprocesses and tools/services identified is a first step towards development of a generic framework or architecture for sharing of data from clinical trials. Such a framework is strongly needed to give an overview of how various actors, research processes and services could form an interoperable system for data sharing.
      PubDate: 2018-02-01T16:15:47Z
      DOI: 10.12688/f1000research.13789.1
      Issue No: Vol. 7 (2018)
  • How to prevent the next Marathon Pharmaceuticals [version 1; referees: 2
           approved, 1 approved with reservations]

    • Authors: Frank S. David, Richa Dixit
      Abstract: In recent years, several drug companies have exploited U.S. regulatory policies to acquire exclusive rights to cheap therapies and substantially raise their prices, and Federal agencies and state governments are exploring various ways to prevent or punish such behavior in the future. Among these cases, however, Marathon Pharmaceuticals’ handling of Emflaza (deflazacort) is unique, because the drug was previously only available abroad, and was never previously sold in the U.S. before the company obtained FDA approval for it. Thus, laws and policies designed to address price hikes on already-marketed drugs are unlikely to prevent additional Marathon-like scenarios. In this article, we describe in more detail the unique features of Emflaza compared with these other recent cases of drug price increases, determine the likelihood that similar situations will arise in the future, and explore legislative and administrative options to specifically prevent such behavior.
      PubDate: 2018-01-17T12:41:48Z
      DOI: 10.12688/f1000research.13678.1
      Issue No: Vol. 7 (2018)
  • Improving communication for interdisciplinary teams working on storage of
           digital information in DNA [version 1; referees: 2 approved]

    • Authors: Emily E. Hesketh, Jossy Sayir, Nick Goldman
      Abstract: Close collaboration between specialists from diverse backgrounds and working in different scientific domains is an effective strategy to overcome challenges in areas that interface between biology, chemistry, physics and engineering. Communication in such collaborations can itself be challenging.  Even when projects are successfully concluded, resulting publications — necessarily multi-authored — have the potential to be disjointed. Few, both in the field and outside, may be able to fully understand the work as a whole. This needs to be addressed to facilitate efficient working, peer review, accessibility and impact to larger audiences. We are an interdisciplinary team working in a nascent scientific area, the repurposing of DNA as a storage medium for digital information. In this note, we highlight some of the difficulties that arise from such collaborations and outline our efforts to improve communication through a glossary and a controlled vocabulary and accessibility via short plain-language summaries. We hope to stimulate early discussion within this emerging field of how our community might improve the description and presentation of our work to facilitate clear communication within and between research groups and increase accessibility to those not familiar with our respective fields — be it molecular biology, computer science, information theory or others that might become relevant in future. To enable an open and inclusive discussion we have created a glossary and controlled vocabulary as a cloud-based shared document and we invite other scientists to critique our suggestions and contribute their own ideas.
      PubDate: 2018-01-10T12:17:46Z
      DOI: 10.12688/f1000research.13482.1
      Issue No: Vol. 7 (2018)
  • archiDART v3.0: A new data analysis pipeline allowing the topological
           analysis of plant root systems [version 1; referees: 2 approved, 1
           approved with reservations]

    • Authors: Benjamin M. Delory, Mao Li, Christopher N. Topp, Guillaume Lobet
      Abstract: Quantifying plant morphology is a very challenging task that requires methods able to capture the geometry and topology of plant organs at various spatial scales. Recently, the use of persistent homology as a mathematical framework to quantify plant morphology has been successfully demonstrated for leaves, shoots, and root systems. In this paper, we present a new data analysis pipeline implemented in the R package archiDART to analyse root system architectures using persistent homology. In addition, we also show that both geometric and topological descriptors are necessary to accurately compare root systems and assess their natural complexity.
      PubDate: 2018-01-08T13:49:11Z
      DOI: 10.12688/f1000research.13541.1
      Issue No: Vol. 7 (2018)
  • Monocytes isolated by positive and negative magnetic sorting techniques
           show different molecular characteristics and immunophenotypic behaviour
           [version 3; referees: 2 approved]

    • Authors: Jashdeep Bhattacharjee, Barun Das, Alaknanda Mishra, Preeti Sahay, Pramod Upadhyay
      Abstract: Background: Magnetic sorting of cells, based on  microbead conjugated antibodies (Abs), employs positive as well as negative immunomagnetic separation methods, for isolation of a specific cell population. These microbeads are suggested to be nontoxic, biodegradable carriers conjugated to various antibodies. Isolation of cells through positive selection involves the attachment of antibody conjugated microbeads to the cells of interest, followed by their isolation in the presence of a strong magnetic field to obtain higher purity. Negative selection involves attachment of microbead conjugated antibodies to all other cell populations except the cells of interest, which remain untagged. In the present study, we compared the two methods for their effect on functional and immunophenotypic behavior of isolated CD14+ monocytes. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from blood collected from healthy volunteers by density gradient centrifugation. Human blood derived monocytes were isolated through positive selection and negative selection, making use of the appropriate monocyte isolation kit. Monocytes were then stimulated with lipopolysaccharide (LPS) and their activation and proliferation capacity were examined. The degradation or dissociation of cell-bound microbeads was also investigated. Results: We observed an impaired LPS sensitivity as well as poor activation and proliferation capacity upon stimulation by LPS in positively sorted CD14+ monocytes as compared to negatively sorted CD14+ monocytes. The attached microbeads did not degrade and remained attached to the cells even after 6 days of culture. Conclusions: Our results suggest that positively sorted CD14+ cells exhibit hampered functionality and may result in inaccurate analysis and observations in downstream applications. However, these cells can be used for immediate analytical procedures.
      PubDate: 2018-03-28T13:42:50Z
      DOI: 10.12688/f1000research.12802.3
      Issue No: Vol. 6 (2018)
  • Case Report: A rare case of prosthetic valve infective endocarditis caused
           by Aerococcus urinae [version 3; referees: 2 approved]

    • Authors: Muhammad Adeel, Saman Tariq, Hisham Akthar, Ahmed Zaghloul, Corina Iorgoveanu, Carina Dehner
      Abstract: Infective endocarditis (IE) is a serious and life-threatening cardiac condition, most commonly caused by staphylococci, Streptococcus viridans, and enterococci. However, in special settings, IE can be caused by rare organisms. Here we present a case of IE caused by Aerococcus urinae in a 75-year-old man with a bioprosthetic aortic valve.  Aerococcus urinae is a gram-positive, catalase-negative microorganism and is usually an isolate of complicated urinary tract infections in the elderly male population.  Improvements in diagnostic testing including use of matrix-assisted laser desorption ionization– a time of flight mass spectrometry (MALDI-TOF MS) have played an important role in recognition of Aerococcus urinae.
      PubDate: 2018-03-28T08:04:05Z
      DOI: 10.12688/f1000research.12776.3
      Issue No: Vol. 6 (2018)
  • What do we know about grant peer review in the health sciences'
           [version 2; referees: 2 approved]

    • Authors: Susan Guthrie, Ioana Ghiga, Steven Wooding
      Abstract: Background: Peer review decisions award an estimated>95% of academic medical research funding, so it is crucial to understand how well they work and if they could be improved. Methods: This paper summarises evidence from 105 papers identified through a literature search on the effectiveness and burden of peer review for grant funding. Results: There is a remarkable paucity of evidence about the efficiency of peer review for funding allocation, given its centrality to the modern system of science. From the available evidence, we can identify some conclusions around the effectiveness and burden of peer review. The strongest evidence around effectiveness indicates a bias against innovative research. There is also fairly clear evidence that peer review is, at best, a weak predictor of future research performance, and that ratings vary considerably between reviewers. There is some evidence of age bias and cronyism. Good evidence shows that the burden of peer review is high and that around 75% of it falls on applicants. By contrast, many of the efforts to reduce burden are focused on funders and reviewers/panel members. Conclusions: We suggest funders should acknowledge, assess and analyse the uncertainty around peer review, even using reviewers’ uncertainty as an input to funding decisions. Funders could consider a lottery element in some parts of their funding allocation process, to reduce both burden and bias, and allow better evaluation of decision processes. Alternatively, the distribution of scores from different reviewers could be better utilised as a possible way to identify novel, innovative research. Above all, there is a need for open, transparent experimentation and evaluation of different ways to fund research. This also requires more openness across the wider scientific community to support such investigations, acknowledging the lack of evidence about the primacy of the current system and the impossibility of achieving perfection.
      PubDate: 2018-03-27T14:28:12Z
      DOI: 10.12688/f1000research.11917.2
      Issue No: Vol. 6 (2018)
  • Evaluation of Trichoderma spp., Pseudomonas fluorescens and Bacillus
           subtilis for biological control of Ralstonia wilt of tomato [version 3;
           referees: 2 approved]

    • Authors: Shiva Yendyo, Ramesh G.C., Binayak Raj Pandey
      Abstract: Background: Ralstonia spp. is a major pathogenic microbe for tomato, which invades the roots of diverse plant hosts and colonizes xylem vessels causing wilt, especially in tropical, subtropical and warm-temperate regions. Ralstonia spp. produces several virulence factors helping it to invade the plant’s natural defense mechanism. Native isolates of Trichoderma spp., Pseudomonas fluorescens and Bacillus subtilis can be used as biocontrol agents to control the bacterial wilt and combined application of these beneficial microbes can give better results. Methods: Bacterial wilt infection in the field was identified by field experts and the infected plant part was used to isolate Ralstonia spp. in CPG media and was positively identified. Subsequently, the efficacy of the biocontrol agents was tested and documented using agar well diffusion technique and digital microscopy. 2ml of the microbial concentrate (109 cells/ml) was mixed in one liter of water and was applied in the plant root at the rate of 100 ml per plant as a treatment method. Results: It was observed that the isolated Trichoderma spp. AA2 and Pseudomonas fluorescens PFS were most potent in inhibiting the growth of Ralstonia spp., showing ZOI 20.67 mm and 22.33 mm, respectively. Digital microscopy showed distinct inhibitory effect on the growth and survival of Ralstonia spp. The results from the field data indicated that Trichoderma spp. and Pseudomonas fluorescens alone were able to prevent 92% and 96% of the infection and combination of both were more effective, preventing 97% of infection. Chemical control methods prevented 94% of infection. Bacillus subtilis could only prevent 84 % of the infection.   Conclusions: Antagonistic effect against Ralstonia spp. shown by native isolates of Trichoderma spp. and P. fluorescens manifested the promising potential as biocontrol agents. Combined application gave better results. Results shown by Bacillus subtilis were not significant.
      PubDate: 2018-03-22T08:54:39Z
      DOI: 10.12688/f1000research.12448.3
      Issue No: Vol. 6 (2018)
  • Rapid coral mortality following unusually calm and hot conditions on
           Iriomote, Japan [version 2; referees: 2 approved]

    • Authors: Andrew H Baird, Sally A. Keith, Erika Woolsey, Ryuta Yoshida, Tohru Naruse
      Abstract: Coral bleaching can be induced by many different stressors, however, the most common cause of mass bleaching in the field is higher than average sea surface temperatures (SST). Here, we describe an unusual bleaching event that followed very calm sea conditions combined with higher than average SST. Patterns of mortality differed from typical bleaching in four ways: 1) mortality was very rapid; 2) a different suite of species were most affected; 3) tissue mortality in Acropora spp. was often restricted to the center of the colony; 4) the event occurred early in summer. The two weeks prior to the event included 8 days where the average wind speed was less than 3 ms-1. In addition, SSTs in the weeks preceding and during the event were 1.0-1.5°C higher than the mean for the last 30 years. We hypothesize that this unusual bleaching event was caused by anoxia resulting from a lack of water movement induced by low wind speeds combined with high SST.
      PubDate: 2018-03-12T16:23:17Z
      DOI: 10.12688/f1000research.12660.2
      Issue No: Vol. 6 (2018)
  • Mitochondrial dysfunction in an animal model of diabetic neuropathy is
           associated with a reduction of neurosteroid synthesis. [version 2;
           referees: 2 approved]

    • Authors: Stephen R. Humble
      Abstract: Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABAAR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO). This study explored the differential effect of diazepam on GABAAR modulation via neurosteroidogenesis in diabetic and wild type (WT) mice. Methods: Whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from layer 2/3 cortical pyramidal neurons of the pain pathway from mice with type-II diabetic neuropathy (ob/ob) and WT controls aged 60-80 days. Results: There was a key difference in the response of the WT and ob/ob cortical neurons to simultaneous incubation with diazepam and flumazenil. In contrast, diazepam and the 5a-reductase inhibitor finasteride, individually or in combination, produced the same response in both strains. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABAAR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathy, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit.
      PubDate: 2018-03-09T12:12:44Z
      DOI: 10.12688/f1000research.11056.2
      Issue No: Vol. 6 (2018)
  • Continuous training and certification in neonatal resuscitation in remote
           areas using a multi-platform information and communication technology
           intervention, compared to standard training: A randomized cluster trial
           study protocol [version 3; referees: 2 approved]

    • Authors: Carlos Alberto Delgado, Enrique M. Gómez Pomar, Pablo Velásquez, Víctor Sánchez, Roberto Shimabuku, Luis Huicho, RCPNEOPERU Study Group
      Abstract: Background: About 10% of all newborns may have difficulty breathing and require support by trained personnel. In Peru, 90% of deliveries occur in health facilities. However, there is not a national neonatal resuscitation and certification program for the public health sector. In addition, the Andes and the Amazon regions concentrate large rural remote areas, which further limit the implementation of training programs and the accomplishment of continuous certification. Neonatal resuscitation training through the use of information, communication and technology (ICT) tools running on computers, tablets or mobile phones, may overcome such limitations. This strategy allows online and offline access to educational resources, paving the way to more frequent and efficient training and certification processes. Objective: To evaluate the effects of a neonatal resuscitation training and certification program that uses a multi-platform ICT (MP-ICT) strategy on neonatal health care in remote areas. Methods: We propose to conduct the study through a cluster-randomized trial, where the study and analysis unit is the health care facility. Eligible facilities will include primary and secondary health care level facilities that are located in provinces with neonatal mortality rates higher than 15 per 1,000 live births. We will compare the proportion of newborns with a heart rate ≥100 beats per minute at two minutes after birth in health care facilities that receive MP-ICT training and certification implementation, with those that receive standard training and certification. Discussion: We expect that the intervention will be shown as more effective than the current standard of care. We are prepared to include it within a national neonatal resuscitation training and certification program to be implemented at national scale together with policymakers and other key stakeholders.  Trial registration: Nº NCT03210194  Status of the study: This study is enrolling participants by invitation only. Study protocol version 1.1 – March 31st, 2017
      PubDate: 2018-03-08T09:01:17Z
      DOI: 10.12688/f1000research.12269.3
      Issue No: Vol. 6 (2018)
  • A comparison of spatial heterogeneity with local cluster detection methods
           for chronic respiratory diseases in Thailand [version 2; referees: 2

    • Authors: Wongsa Laohasiriwong, Nattapong Puttanapong, Amornrat Luenam
      Abstract: Background: The Centers for Disease Control and Prevention reported that deaths from chronic respiratory diseases (CRDs) in Thailand increased by almost 13% in 2010, along with an increased burden related to the disease. Evaluating the geographical heterogeneity of CRDs is important for surveillance. Previous studies have indicated that socioeconomic status has an effect on disease, and that this can be measured with variables such as night-time lights (NTLs) and industrial density (ID). However, there is no understanding of how NTLs and ID correlate with CRDs. We compared spatial heterogeneity obtained by using local cluster detection methods for CRDs and by correlating NTLs and ID with CRDs. Methods: We applied the spatial scan statistic in SaTScan, as well as local indices of spatial association (LISA), Getis and Ord’s local Gi*(d) statistic, and Pearson correlation. In our analysis, data were collected on gender, age, household income, education, family size, occupation, region, residential area, housing construction materials, cooking fuels, smoking status and previously diagnosed CRDs by a physician from the National Socioeconomic Survey, which is a cross-sectional study conducted by the National Statistical Office of Thailand in 2010. Results: According to our findings, the spatial scan statistic, LISA, and the local Gi*(d) statistic revealed similar results for areas with the highest clustering of CRDs. However, the hotspots for the spatial scan statistic covered a wider area than LISA and the local Gi*(d) statistic. In addition, there were persistent hotspots in Bangkok and the perimeter provinces. NTLs and ID have a positive correlation with CRDs. Conclusions: This study demonstrates that all the statistical methods used could detect spatial heterogeneity of CRDs. NTLs and ID can serve as new parameters for determining disease hotspots by representing the population and industrial boom that typically contributes to epidemics.
      PubDate: 2018-03-06T09:31:56Z
      DOI: 10.12688/f1000research.12128.2
      Issue No: Vol. 6 (2018)
  • Endoplasmic reticulum-to-Golgi transitions upon herpes virus infection
           [version 2; referees: 1 approved, 3 approved with reservations]

    • Authors: Peter Wild, Andres Kaech, Elisabeth M. Schraner, Ladina Walser, Mathias Ackermann
      Abstract: Background: Herpesvirus capsids are assembled in the nucleus, translocated to the perinuclear space by budding, acquiring tegument and envelope, or released to the cytoplasm via impaired nuclear envelope. One model proposes that envelopment, “de-envelopment” and “re-envelopment” is essential for production of infectious virus. Glycoproteins gB/gH were reported to be essential for de-envelopment, by fusion of the “primary” envelope with the outer nuclear membrane. Yet, a high proportion of enveloped virions generated from genomes with deleted gB/gH were found in the cytoplasm and extracellular space, suggesting the existence of alternative exit routes. Methods: We investigated the relatedness between the nuclear envelope and membranes of the endoplasmic reticulum and Golgi complex, in cells infected with either herpes simplex virus 1 (HSV-1) or a Us3 deletion mutant thereof, or with bovine herpesvirus 1 (BoHV-1) by transmission and scanning electron microscopy, employing freezing technique protocols. Results:  The Golgi complex is a compact entity in a juxtanuclear position covered by a membrane on the cis face. Golgi membranes merge with membranes of the endoplasmic reticulum forming an entity with the perinuclear space. All compartments contained enveloped virions. After treatment with brefeldin A, HSV-1 virions aggregated in the perinuclear space and endoplasmic reticulum, while infectious progeny virus was still produced. Conclusions: The data suggest that virions derived by budding at nuclear membranes are intraluminally transported from the perinuclear space via Golgi -endoplasmic reticulum transitions into Golgi cisternae for packaging. Virions derived by budding at nuclear membranes are infective like Us3 deletion mutants, which  accumulate in the perinuclear space. Therefore, i) de-envelopment followed by re-envelopment is not essential for production of infective progeny virus, ii) the process taking place at the outer nuclear membrane is budding not fusion, and iii) naked capsids gain access to the cytoplasmic matrix via impaired nuclear envelope as reported earlier.
      PubDate: 2018-02-28T16:45:30Z
      DOI: 10.12688/f1000research.12252.2
      Issue No: Vol. 6 (2018)
  • Rheumatoid arthritis in an adult patient with mosaic distal 18q-, 18p- and
           ring chromosome 18 [version 2; referees: 2 approved]

    • Authors: Alanna Chau, KH Ramesh, Anand D Jagannath, Shitij Arora
      Abstract: Ring chromosome 18 has a highly variable phenotype, depending on the extent of distal arm deletions. It is most commonly presented as a combination of 18p- and distal 18q- syndrome. IgA deficiency and autoimmune diseases have been previously described in these patients. Seven cases of juvenile rheumatoid arthritis (JRA) have been reported. Here we report the first case of late onset rheumatoid arthritis (RA) in a 32 year old Dominican woman with hypothyroidism, vitiligo, IgA deficiency, interstitial lung disease (ILD), cystic bronchiectasis, and features consistent with ringed 18, 18p- and distal 18q syndrome.  The multiple autoimmune findings in our patient lends further support to the idea of loci on chromosome 18 playing a role in autoimmune disease expression. Late onset RA and ILD in a patient with chromosome 18 abnormalities are novel findings and are additional conditions to be aware of in this population.
      PubDate: 2018-02-28T10:55:08Z
      DOI: 10.12688/f1000research.11539.2
      Issue No: Vol. 6 (2018)
  • Maize Phyllosphere Microbial Community Niche Development Across Stages of
           Host Leaf Growth [version 3; referees: 2 approved, 1 approved with

    • Authors: Heather C. Manching, Kara Carlson, Sean Kosowsky, C. Tyler Smitherman, Ann E. Stapleton
      Abstract: Background: The phyllosphere hosts a variety of microorganisms, including bacteria, which can play a positive role in the success of the host plant. Bacterial communities in the phylloplane are influenced by both biotic and abiotic factors, including host plant surface topography and chemistry, which change in concert with microbial communities as the plant leaves develop and age. Methods: We examined how the Zea mays L. leaf microbial community structure changed with plant age. Ribosomal spacer length and scanning electron microscopic imaging strategies were used to assess microbial community composition across maize plant ages, using a novel staggered experimental design. Results: Significant changes in community composition were observed for both molecular and imaging analyses, and the two analysis methods provided complementary information about bacterial community structure within each leaf developmental stage. Conclusions: Both taxonomic and cell-size trait patterns provided evidence for niche-based contributions to microbial community development on leaves.
      PubDate: 2018-01-18T16:14:32Z
      DOI: 10.12688/f1000research.12490.3
      Issue No: Vol. 6 (2018)
  • MSL: Facilitating automatic and physical analysis of published scientific
           literature in PDF format [version 3; referees: 1 approved, 3 approved with

    • Authors: Zeeshan Ahmed, Thomas Dandekar
      Abstract: Published scientific literature contains millions of figures, including information about the results obtained from different scientific experiments e.g. PCR-ELISA data, microarray analysis, gel electrophoresis, mass spectrometry data, DNA/RNA sequencing, diagnostic imaging (CT/MRI and ultrasound scans), and medicinal imaging like electroencephalography (EEG), magnetoencephalography (MEG), echocardiography  (ECG), positron-emission tomography (PET) images. The importance of biomedical figures has been widely recognized in scientific and medicine communities, as they play a vital role in providing major original data, experimental and computational results in concise form. One major challenge for implementing a system for scientific literature analysis is extracting and analyzing text and figures from published PDF files by physical and logical document analysis. Here we present a product line architecture based bioinformatics tool ‘Mining Scientific Literature (MSL)’, which supports the extraction of text and images by interpreting all kinds of published PDF files using advanced data mining and image processing techniques. It provides modules for the marginalization of extracted text based on different coordinates and keywords, visualization of extracted figures and extraction of embedded text from all kinds of biological and biomedical figures using applied Optimal Character Recognition (OCR). Moreover, for further analysis and usage, it generates the system’s output in different formats including text, PDF, XML and images files. Hence, MSL is an easy to install and use analysis tool to interpret published scientific literature in PDF format.
      PubDate: 2018-04-04T15:45:54Z
      DOI: 10.12688/f1000research.7329.3
      Issue No: Vol. 4 (2018)
  • Collaboration between a human group and artificial intelligence can
           improve prediction of multiple sclerosis course: a proof-of-principle
           study [version 1; referees: 1 approved, 2 approved with reservations]

    • Authors: Andrea Tacchella, Silvia Romano, Michela Ferraldeschi, Marco Salvetti, Andrea Zaccaria, Andrea Crisanti, Francesca Grassi
      Abstract: Background: Multiple sclerosis has an extremely variable natural course. In most patients, disease starts with a relapsing-remitting (RR) phase, which proceeds to a secondary progressive (SP) form. The duration of the RR phase is hard to predict, and to date predictions on the rate of disease progression remain suboptimal. This limits the opportunity to tailor therapy on an individual patient's prognosis, in spite of the choice of several therapeutic options. Approaches to improve clinical decisions, such as collective intelligence of human groups and machine learning algorithms are widely investigated. Methods: Medical students and a machine learning algorithm predicted the course of disease on the basis of randomly chosen clinical records of patients that attended at the Multiple Sclerosis service of Sant'Andrea hospital in Rome. Results: A significant improvement of predictive ability was obtained when predictions were combined with a weight that depends on the consistence of human (or algorithm) forecasts on a given clinical record. Conclusions: In this work we present proof-of-principle that human-machine hybrid predictions yield better prognoses than machine learning algorithms or groups of humans alone. To strengthen this preliminary result, we propose a crowdsourcing initiative to collect prognoses by physicians on an expanded set of patients.
      PubDate: 2017-12-22T14:35:45Z
      DOI: 10.12688/f1000research.13114.1
      Issue No: Vol. 6 (2017)
  • New chimeric RNAs in acute myeloid leukemia [version 2; referees: 2

    • Authors: Florence Rufflé, Jerome Audoux, Anthony Boureux, Sacha Beaumeunier, Jean-Baptiste Gaillard, Elias Bou Samra, Andre Megarbane, Bruno Cassinat, Christine Chomienne, Ronnie Alves, Sebastien Riquier, Nicolas Gilbert, Jean-Marc Lemaitre, Delphine Bacq-Daian, Anne Laure Bougé, Nicolas Philippe, Therese Commes
      Abstract: Background: High-throughput next generation sequencing (NGS) technologies enable the detection of biomarkers used for tumor classification, disease monitoring and cancer therapy. Whole-transcriptome analysis using RNA-seq is important, not only as a means of understanding the mechanisms responsible for complex diseases but also to efficiently identify novel genes/exons, splice isoforms, RNA editing, allele-specific mutations, differential gene expression and fusion-transcripts or chimeric RNA (chRNA). Methods: We used Crac, a tool that uses genomic locations and local coverage to classify biological events and directly infer splice and chimeric junctions within a single read. Crac’s algorithm extracts transcriptional chimeric events irrespective of annotation with a high sensitivity, and CracTools was used to aggregate, annotate and filter the chRNA reads. The selected chRNA candidates were validated by real time PCR and sequencing.  In order to check the tumor specific expression of chRNA, we analyzed a publicly available dataset using a new tag search approach. Results:  We present data related to acute myeloid leukemia (AML) RNA-seq analysis. We highlight novel biological cases of chRNA, in addition to previously well characterized leukemia chRNA. We have identified and validated 17 chRNAs among 3 AML patients: 10 from an AML patient with a translocation between chromosomes 15 and 17 (AML-t(15;17), 4  from patient with normal karyotype (AML-NK) 3 from a patient with chromosomal 16 inversion (AML-inv16). The new fusion transcripts can be classified into four groups according to the exon organization. Conclusions:  All groups suggest complex but distinct synthesis mechanisms involving either collinear exons of different genes, non-collinear exons, or exons of different chromosomes. Finally, we check tumor-specific expression in a larger RNA-seq AML cohort and identify new AML biomarkers that could improve diagnosis and prognosis of AML.
      PubDate: 2017-12-19T11:06:14Z
      DOI: 10.12688/f1000research.11352.2
      Issue No: Vol. 6 (2017)
  • Socioeconomic disparities in income, education and geographic location for
           hypertension among Thai adults: Results from the National Socioeconomic
           Survey [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Atthawit Singsalasang, Wongsa Laohasiriwong, Nattapong Puttanapong, Teerasak Phajan, Suwanna Boonyaleephan
      Abstract: Background: Hypertension (HT) has been one of the leading global risk factors for health and the leading cause of death in Thailand for decades. The influence of socioeconomic factors on HT has been varied and inconclusive. The aim of this study was to determine the association between socioeconomic determinants and HT in Thailand. Methods: This study used data from the National Socioeconomic Survey, a cross-sectional study that was conducted by the National Statistical Office of Thailand in the years 2005, 2006 and 2007. In our analysis, data were collected on gender, age, marital status, smoking status, education, status of work, occupation, current liability (short-term debt), household monthly income, residential area, region and previously diagnosed HT by a physician. Results: The odds of having HT were significantly higher among those who had household monthly income, education, residential area and region. The participants who had monthly income of
      PubDate: 2017-10-13T14:00:02Z
      DOI: 10.12688/f1000research.12709.1
      Issue No: Vol. 6 (2017)
  • Case Report: Mucus plug in bronchus mimicking a bronchial solid foreign
           body obstruction [version 1; referees: 2 approved]

    • Authors: Kiran Devkota, Miao He, You Wei Zhang
      Abstract: Bronchial foreign body obstruction is common in all clinical settings. Obstruction of the airway due to foreign bodies and foreign body aspiration are major causes of childhood mortality and morbidity, which are a big challenge to manage. Occasionally, bronchial obstruction may be due to mucus plugs or other endogenous factors. Here we describe a case of bronchial obstruction caused by mucus plug formation that was managed conservatively in a one-year old boy. The patient was suffering from a cough and noisy breathing for 2 days prior to coming to our hospital, when he experienced sudden onset of difficulty in breathing and a severe cough. At the time of presentation his vital sign readings were:- HR 186 bpm, RR 46/min, BP 78/40 MmHg, temp 36.9°C and SPO2 68%. He was given oxygen immediately and nebulization was started. Chest CT scan was performed that suggested the presence of a right bronchial foreign body with right sided obstructive emphysema. The patient was stable with oxygenation and nebulization with ipratropium bromide, albuterol, normal saline and budesonide before the CT scan. Therefore, we conclude that symptoms resembling foreign body obstruction are not always aspirated or inhaled, and sometimes secreted sputum forms a plug, which mimics the symptoms of foreign body obstruction.
      PubDate: 2017-09-25T15:07:48Z
      DOI: 10.12688/f1000research.12495.1
      Issue No: Vol. 6 (2017)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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Fax: +00 44 (0)131 4513327
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