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Journal Cover F1000Research
  [SJR: 0.56]   [H-I: 9]   [4 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Antigen-specific Treg cells in immunological tolerance: implications for
           allergic diseases [version 1; referees: 3 approved]

    • Authors: Azza Abdel-Gadir, Amir H. Massoud, Talal A. Chatila
      Abstract: Allergic diseases are chronic inflammatory disorders in which there is failure to mount effective tolerogenic immune responses to inciting allergens. The alarming rise in the prevalence of allergic diseases in recent decades has spurred investigations to elucidate the mechanisms of breakdown in tolerance in these disorders and means of restoring it. Tolerance to allergens is critically dependent on the generation of allergen-specific regulatory T (Treg) cells, which mediate a state of sustained non-responsiveness to the offending allergen. In this review, we summarize recent advances in our understanding of mechanisms governing the generation and function of allergen-specific Treg cells and their subversion in allergic diseases. We will also outline approaches to harness allergen-specific Treg cell responses to restore tolerance in these disorders.
      PubDate: 2018-01-10T10:55:23Z
      DOI: 10.12688/f1000research.12650.1
      Issue No: Vol. 7 (2018)
  • Recent advances in the management of priapism [version 1; referees: 2

    • Authors: Asif Muneer, Hussain M. Alnajjar, David Ralph
      Abstract: Priapism is an uncommon urological emergency that can lead to permanent impotence if prompt presentation and medical intervention is not performed. It is a breakdown of the usual physiological mechanisms controlling penile tumescence and detumescence, leading to a prolonged penile erection (>4 hours) that is unrelated to sexual stimulation. Currently, there are three accepted subtypes: ischaemic, non-ischaemic, and stuttering priapism, which is also known as recurrent ischemic priapism. The aim of treatment is the immediate resolution of the painful erection and the preservation of cavernosal smooth muscle function in order to prevent cavernosal fibrosis, which can lead to penile shortening and permanent erectile dysfunction.
      PubDate: 2018-01-10T10:20:30Z
      DOI: 10.12688/f1000research.12828.1
      Issue No: Vol. 7 (2018)
  • Inhibitory control of the excitatory/inhibitory balance in psychiatric
           disorders [version 1; referees: 2 approved]

    • Authors: Martijn Selten, Hans van Bokhoven, Nael Nadif Kasri
      Abstract: Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.
      PubDate: 2018-01-08T14:30:44Z
      DOI: 10.12688/f1000research.12155.1
      Issue No: Vol. 7 (2018)
  • Molecular mechanisms of macrophage Toll-like receptor–Fc receptor
           synergy [version 1; referees: 2 approved]

    • Authors: Michelle Lennartz, James Drake
      Abstract: Macrophages (MØs) are a key cell type of both the innate and the adaptive immune response and can tailor their response to prevailing conditions. To sense the host’s status, MØs employ two classes of receptors: Toll-like receptors (TLRs), which are sensors for pathogen-derived material, and Fcγ receptors (FcγRs) that are detectors of the adaptive immune response. How MØs integrate the input from these various sensors is not understood and is the focus of active study. Here, we review the recent literature on the molecular mechanisms of TLR and FcgR crosstalk and synergy, and discuss the implications of these findings. This overview suggests a multilayered mechanism of receptor synergy that allows the MØ to fine-tune its response to prevailing conditions and provides ideas for future investigation.
      PubDate: 2018-01-08T12:05:09Z
      DOI: 10.12688/f1000research.12679.1
      Issue No: Vol. 7 (2018)
  • How anthropogenic shifts in plant community composition alter soil food
           webs [version 1; referees: 2 approved]

    • Authors: Paul Kardol, Jonathan R. De Long
      Abstract: There are great concerns about the impacts of soil biodiversity loss on ecosystem functions and services such as nutrient cycling, food production, and carbon storage. A diverse community of soil organisms that together comprise a complex food web mediates such ecosystem functions and services. Recent advances have shed light on the key drivers of soil food web structure, but a conceptual integration is lacking. Here, we explore how human-induced changes in plant community composition influence soil food webs. We present a framework describing the mechanistic underpinnings of how shifts in plant litter and root traits and microclimatic variables impact on the diversity, structure, and function of the soil food web. We then illustrate our framework by discussing how shifts in plant communities resulting from land-use change, climatic change, and species invasions affect soil food web structure and functioning. We argue that unravelling the mechanistic links between plant community trait composition and soil food webs is essential to understanding the cascading effects of anthropogenic shifts in plant communities on ecosystem functions and services.
      PubDate: 2018-01-02T14:08:13Z
      DOI: 10.12688/f1000research.13008.1
      Issue No: Vol. 7 (2018)
  • Vancomycin-resistant enterococcus infection in the hematopoietic stem cell
           transplant recipient: an overview of epidemiology, management, and
           prevention [version 1; referees: 3 approved]

    • Authors: Esther Benamu, Stanley Deresinski
      Abstract: Vancomycin-resistant enterococcus (VRE) is now one of the leading causes of nosocomial infections in the United States. Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of VRE colonization and infection. VRE has emerged as a major cause of bacteremia in this population, raising important clinical questions regarding the role and impact of VRE colonization and infection in HSCT outcomes as well as the optimal means of prevention and treatment. We review here the published literature and scientific advances addressing these thorny issues and provide a rational framework for their approach.
      PubDate: 2018-01-02T13:51:26Z
      DOI: 10.12688/f1000research.11831.1
      Issue No: Vol. 7 (2018)
  • The rise and fall of machine learning methods in biomedical research
           [version 2; referees: 2 approved]

    • Authors: Hashem Koohy
      Abstract: In the era of explosion in biological data, machine learning techniques are becoming more popular in life sciences, including biology and medicine. This research note examines the rise and fall of the most commonly used machine learning techniques in life sciences over the past three decades.
      PubDate: 2018-01-02T10:18:43Z
      DOI: 10.12688/f1000research.13016.2
      Issue No: Vol. 6 (2018)
  • Recent advances in the biology and therapy of medullary thyroid carcinoma
           [version 1; referees: 2 approved]

    • Authors: Barry Nelkin
      Abstract: Medullary thyroid cancer (MTC) is a relatively uncommon yet prognostically significant thyroid cancer. Several recent advances in the biology and current or potential treatment of MTC are notable. These include a new understanding of the developmental biology of the thyroid C cell, which heretofore was thought to develop from the neural crest. RET, encoded by the most common driver gene in MTC, has been shown to be a dual function kinase, thus expanding its potential substrate repertoire. Promising new therapeutic developments are occurring; many have recently progressed to clinical development. There are new insights into RET inhibitor therapy for MTC. New strategies are being developed to inhibit the RAS proteins, which are potential therapeutic targets in MTC. Potential emerging immunotherapies for MTC are discussed. However, gaps in our knowledge of the basic biology of the C cell, its transformation to MTC, and the mechanisms of resistance to therapy impede progress; further research in these areas would have a substantial impact on the field.
      PubDate: 2017-12-28T14:22:09Z
      DOI: 10.12688/f1000research.12645.1
      Issue No: Vol. 6 (2017)
  • The peer review process for awarding funds to international science
           research consortia: a qualitative developmental evaluation [version 2;
           referees: 2 approved]

    • Authors: Stefanie Gregorius, Laura Dean, Donald C Cole, Imelda Bates
      Abstract: Background: Evaluating applications for multi-national, multi-disciplinary, dual-purpose research consortia is highly complex. There has been little research on the peer review process for evaluating grant applications and almost none on how applications for multi-national consortia are reviewed. Overseas development investments are increasingly being channelled into international science consortia to generate high-quality research while simultaneously strengthening multi-disciplinary research capacity. We need a better understanding of how such decisions are made and their effectiveness. Methods: An award-making institution planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out of 78 eligible applications were shortlisted and reviewed by at least five external reviewers before final selections were made by a face-to-face panel. We used an innovative approach involving structured, overt observations of award-making panel meetings and semi-structured interviews with panel members to explore how assessment criteria concerning research quality and capacity strengthening were applied during the peer review process. Data were coded and analysed using pre-designed matrices which incorporated categories relating to the assessment criteria. Results: In general the process was rigorous and well-managed. However, lack of clarity about differential weighting of criteria and variations in the panel’s understanding of research capacity strengthening resulted in some inconsistencies in use of the assessment criteria. Using the same panel for both rounds had advantages, in that during the second round consensus was achieved more quickly and the panel had increased focus on development aspects. Conclusion: Grant assessment panels for such complex research applications need to have topic- and context-specific expertise. They must also understand research capacity issues and have a flexible but equitable and transparent approach. This study has developed and tested an approach for evaluating the operation of such panels and has generated lessons that can promote coherence and transparency among grant-makers and ultimately make the award-making process more effective.
      PubDate: 2017-12-22T15:11:44Z
      DOI: 10.12688/f1000research.12496.2
      Issue No: Vol. 6 (2017)
  • The impact of fresh gas flow on wash-in, wash-out time and gas consumption
           for sevoflurane and desflurane, comparing two anaesthesia machines, a
           test-lung study. [version 2; referees: 2 approved, 1 approved with

    • Authors: Fredrik Leijonhufvud, Fredrik Jöneby, Jan G. Jakobsson
      Abstract: Low-flow anaesthesia is considered beneficial for the patient and the environment, and it is cost reducing due to reduced anaesthetic gas consumption. An initial high-flow to saturate the circle system ( wash-in) is desirable from a clinical point of view. We measured the wash-in and wash-out times (time to saturate and to eliminate the anaesthetic agent, AA), for sevoflurane and desflurane, in a test-lung with fixed 3 MAC vaporizer setting at different fresh gas flow (FGF) and calculated the consumption of AA. We tried to find an optimal flow rate for speed and gas consumption, comparing two anaesthesia machines (AMs): Aisys and Flow-i. Time to reach 1 minimal alveolar concentration (MAC) (wash-in) decreased (p
      PubDate: 2017-12-22T14:43:32Z
      DOI: 10.12688/f1000research.13064.2
      Issue No: Vol. 6 (2017)
  • Sleep apnea and its role in transportation safety [version 1; referees: 3

    • Authors: Maria Bonsignore
      Abstract: Obstructive sleep apnea (OSA) is a main cause of excessive daytime sleepiness and increases the risk for driving accidents, which can be normalized by treatment with continuous positive airway pressure ventilation. Since it is estimated that OSA is not diagnosed in about 80% of cases, recognition of patients at risk for driving accidents is a problem from both medical and societal points of view. Strategies to screen and identify subjects at high risk for driving accidents are under study in order to improve safety on the road, especially for commercial drivers, who show a high prevalence of OSA.
      PubDate: 2017-12-22T09:45:34Z
      DOI: 10.12688/f1000research.12599.1
      Issue No: Vol. 6 (2017)
  • The use of dexmedetomidine and intravenous acetaminophen for the
           prevention of postoperative delirium in cardiac surgery patients over 60
           years of age: a pilot study [version 2; referees: 2 approved, 1 not

    • Authors: Ammu T. Susheela, Senthil Packiasabapathy, Doris-Vanessa Gasangwa, Melissa Patxot, Jason O’Neal, Edward Marcantonio, Balachundhar Subramaniam
      Abstract: Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and estimate the effect size for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who completed the study. Results: All patients completed the study successfully. The total incidence of delirium in the study population was 42% (5/12):  67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in  D+A group and 0%(0/3)  P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean range of duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension (systolic blood pressure
      PubDate: 2017-12-21T16:35:48Z
      DOI: 10.12688/f1000research.12552.2
      Issue No: Vol. 6 (2017)
  • Use of electroanalgesia and laser therapies as alternatives to opioids for
           acute and chronic pain management [version 1; referees: 2 approved]

    • Authors: Paul F. White, Ofelia Loani Elvir Lazo, Lidia Galeas, Xuezhao Cao
      Abstract: The use of opioid analgesics for postoperative pain management has contributed to the global opioid epidemic. It was recently reported that prescription opioid analgesic use often continued after major joint replacement surgery even though patients were no longer experiencing joint pain. The use of epidural local analgesia for perioperative pain management was not found to be protective against persistent opioid use in a large cohort of opioid-naïve patients undergoing abdominal surgery. In a retrospective study involving over 390,000 outpatients more than 66 years of age who underwent minor ambulatory surgery procedures, patients receiving a prescription opioid analgesic within 7 days of discharge were 44% more likely to continue using opioids 1 year after surgery. In a review of 11 million patients undergoing elective surgery from 2002 to 2011, both opioid overdoses and opioid dependence were found to be increasing over time. Opioid-dependent surgical patients were more likely to experience postoperative pulmonary complications, require longer hospital stays, and increase costs to the health-care system. The Centers for Disease Control and Prevention emphasized the importance of finding alternatives to opioid medication for treating pain. In the new clinical practice guidelines for back pain, the authors endorsed the use of non-pharmacologic therapies. However, one of the more widely used non-pharmacologic treatments for chronic pain (namely radiofrequency ablation therapy) was recently reported to have no clinical benefit. Therefore, this clinical commentary will review evidence in the peer-reviewed literature supporting the use of electroanalgesia and laser therapies for treating acute pain, cervical (neck) pain, low back pain, persistent post-surgical pain after spine surgery (“failed back syndrome”), major joint replacements, and abdominal surgery as well as other common chronic pain syndromes (for example, myofascial pain, peripheral neuropathic pain, fibromyalgia, degenerative joint disease/osteoarthritis, and migraine headaches).
      PubDate: 2017-12-21T14:47:19Z
      DOI: 10.12688/f1000research.12324.1
      Issue No: Vol. 6 (2017)
  • Predictors of outcome in phaeochromocytomas and paragangliomas [version 1;
           referees: 3 approved]

    • Authors: Marlo Nicolas, Patricia Dahia
      Abstract: Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine-secreting neuroendocrine tumours characterised by high rates of heritability and genetic heterogeneity. Despite advances in the genetic diagnosis and improved understanding of the molecular aberrations underlying these tumours, predictive markers of malignancy remain scarce, limiting the outlook of patients with metastatic PPGL. The identification of robust predictive markers remains the most pressing challenge in PPGL management, so that the potential of targeted therapy to impact patient care can be fully realised.
      PubDate: 2017-12-21T14:45:48Z
      DOI: 10.12688/f1000research.12419.1
      Issue No: Vol. 6 (2017)
  • An RNA decay factor wears a new coat: UPF3B modulates translation
           termination [version 1; referees: 3 approved]

    • Authors: Zhaofeng Gao, Miles Wilkinson
      Abstract: Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that has been subject to intense scrutiny. NMD identifies and degrades subsets of normal RNAs, as well as abnormal mRNAs containing premature termination codons. A core factor in this pathway—UPF3B—is an adaptor protein that serves as an NMD amplifier and an NMD branch-specific factor. UPF3B is encoded by an X-linked gene that when mutated causes intellectual disability and is associated with neurodevelopmental disorders, including schizophrenia and autism. Neu-Yilik et al. now report a new function for UPF3B: it modulates translation termination. Using a fully reconstituted in vitro translation system, they find that UPF3B has two roles in translation termination. First, UPF3B delays translation termination under conditions that mimic premature translation termination. This could drive more efficient RNA decay by allowing more time for the formation of RNA decay-stimulating complexes. Second, UPF3B promotes the dissociation of post-termination ribosomal complexes that lack nascent peptide. This implies that UPF3B could promote ribosome recycling. Importantly, the authors found that UPF3B directly interacts with both RNA and the factors that recognize stop codons—eukaryotic release factors (eRFs)—suggesting that UPF3B serves as a direct regulator of translation termination. In contrast, a NMD factor previously thought to have a central regulatory role in translation termination—the RNA helicase UPF1—was found to indirectly interact with eRFs and appears to act exclusively in post-translation termination events, such as RNA decay, at least in vitro. The finding that an RNA decay-promoting factor, UFP3B, modulates translation termination has many implications. For example, the ability of UPF3B to influence the development and function of the central nervous system may be not only through its ability to degrade specific RNAs but also through its impact on translation termination and subsequent events, such as ribosome recycling.
      PubDate: 2017-12-20T15:57:17Z
      DOI: 10.12688/f1000research.12704.1
      Issue No: Vol. 6 (2017)
  • Recent advances on gradient hydrogels in biomimetic cartilage tissue
           engineering [version 1; referees: 2 approved]

    • Authors: Ivana Gadjanski
      Abstract: Articular cartilage (AC) is a seemingly simple tissue that has only one type of constituting cell and no blood vessels and nerves. In the early days of tissue engineering, cartilage appeared to be an easy and promising target for reconstruction and this was especially motivating because of widespread AC pathologies such as osteoarthritis and frequent sports-induced injuries. However, AC has proven to be anything but simple. Recreating the varying properties of its zonal structure is a challenge that has not yet been fully answered. This caused the shift in tissue engineering strategies toward bioinspired or biomimetic approaches that attempt to mimic and simulate as much as possible the structure and function of the native tissues. Hydrogels, particularly gradient hydrogels, have shown great potential as components of the biomimetic engineering of the cartilaginous tissue.
      PubDate: 2017-12-20T15:31:33Z
      DOI: 10.12688/f1000research.12391.1
      Issue No: Vol. 6 (2017)
  • Pathophysiology and treatment of patients with beta-thalassemia – an
           update [version 1; referees: 2 approved]

    • Authors: Eitan Fibach, Eliezer A. Rachmilewitz
      Abstract: Thalassemia (thal) is an autosomal recessive, hereditary, chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains (α-thal) or β-globin chains (β-thal) that compose the major adult hemoglobin (α2β2). It is caused by one or more mutations in the corresponding genes. The unpaired globin chains are unstable; they precipitate intracellularly, resulting in hemolysis, premature destruction of red blood cell [RBC] precursors in the bone marrow, and a short life-span of mature RBCs in the circulation. The state of anemia is treated by frequent RBC transfusions. This therapy results in the accumulation of iron (iron overload), a condition that is exacerbated by the breakdown products of hemoglobin (heme and iron) and the increased iron uptake for the chronic accelerated, but ineffective, RBC production. Iron catalyzes the generation of reactive oxygen species, which in excess are toxic, causing damage to vital organs such as the heart and liver and the endocrine system. Herein, we review recent findings regarding the pathophysiology underlying the major symptoms of β-thal and potential therapeutic modalities for the amelioration of its complications, as well as new modalities that may provide a cure for the disease.
      PubDate: 2017-12-20T15:07:43Z
      DOI: 10.12688/f1000research.12688.1
      Issue No: Vol. 6 (2017)
  • In vivo genome editing in animals using AAV-CRISPR system: applications to

    • Authors: Cia-Hin Lau, Yousin Suh
      Abstract: Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics.
      PubDate: 2017-12-20T11:38:14Z
      DOI: 10.12688/f1000research.11243.1
      Issue No: Vol. 6 (2017)
  • Better understanding of childhood asthma, towards primary prevention –
           are we there yet' Consideration of pertinent literature [version 1;
           referees: 2 approved]

    • Authors: Michal Gur, Fahed Hakim, Lea Bentur
      Abstract: Asthma is a chronic disease, characterized by reversible airway obstruction, airway inflammation and hyper-reactivity. The prevalence of asthma has risen dramatically over the past decade, affecting around 300,000,000 people. The etiology is multifactorial, with genetic, epigenetic, developmental and environmental factors playing a role. A complex interaction between the intrauterine environment, the developing immune system, the infant's microbiome and infectious organisms may lead to the development of allergic sensitization and asthma. Thus, a large number of studies have investigated the risk factors for childhood asthma, with a meticulous search of modifiable factors that could aid in primary prevention. We present a current literature review from 2014-2017, as well as older classic publications, on the pathogenesis and the potential modifiable factors for primary prevention of asthma. No ideal preventive measure has yet been found. Rather, creating favorable prenatal and postnatal environments, minimal exposure to hostile environmental factors, prevention of infections in early life, allergic desensitization and nutritional modifications could possibly reduce asthma inception. In the era of personalized medicine, identifying individual risk factors and tailoring specific preventive measures is warranted.
      PubDate: 2017-12-20T10:16:26Z
      DOI: 10.12688/f1000research.11601.1
      Issue No: Vol. 6 (2017)
  • Predictive value of early postoperative IOP and bleb morphology in
           Mitomycin-C augmented trabeculectomy [version 2; referees: 2 approved]

    • Authors: Hamed Esfandiari, Mohammad Pakravan, Nils A. Loewen, Mehdi Yaseri
      Abstract: Background: To determine the predictive value of postoperative bleb morphological features and intraocular pressure (IOP) on the success rate of trabeculectomy. Methods: In this prospective interventional case series, we analyzed for one year 80 consecutive primary open angle glaucoma patients who underwent mitomycin-augmented trabeculectomy. Bleb morphology was scored using the Indiana bleb appearance grading scale (IBAGS). Success was defined as IOP ≤15 mmHg at 12 months. We applied a multivariable regression analysis and determined the area under the receiver operating characteristic curve (AUC). Results: The mean age of participants was 62±12.3 years in the success and 63.2±16.3 years in the failure group (P= 0.430) with equal gender distribution (P=0.911). IOPs on day 1, 7 and 30 were similar in both (P= 0.193, 0.639, and 0.238, respectively.) The AUC of IOP at day 1, day 7 and 30 for predicting a successful outcome was 0.355, 0.452, and 0.80, respectively. The AUC for bleb morphology parameters of bleb height, extension, and vascularization, on day 14 were 0.368, 0.408, and 0.549, respectively. Values for day 30 were 0.428, 0.563, and 0.654. IOP change from day 1 to day 30 was a good predictor of failure (AUC=0.838, 95% CI: 0.704 to 0.971) with a change of more than 3 mmHg predicting failure with a sensitivity of 82.5% (95% CI: 68 to 91%) and a specificity of 87.5% (95% CI: 53 to 98%). Conclusions: IOP on day 30 had a fair to good accuracy while bleb features failed to predict success except bleb vascularity that had a poor to fair accuracy.  An IOP increase more than 3 mmHg during the first 30 days was a good predictor of failure.
      PubDate: 2017-12-19T11:14:20Z
      DOI: 10.12688/f1000research.12904.2
      Issue No: Vol. 6 (2017)
  • The stress concept in gastroenterology: from Selye to today [version 1;
           referees: 2 approved]

    • Authors: Sigrid Elsenbruch, Paul Enck
      Abstract: More than eighty years after Hans Selye (1907–1982) first developed a concept describing how different types of environmental stressors affect physiological functions and promote disease development (called the “general adaptation syndrome”) in 1936, we herein review advances in theoretical, mechanistic, and clinical knowledge in stress research, especially in the area of gastroenterology, and summarize progress and future perspectives arising from an interdisciplinary psychoneurobiological framework in which genetics, epigenetics, and other advanced (omics) technologies in the last decade continue to refine knowledge about how stress affects the brain-gut axis in health and gastrointestinal disease. We demonstrate that neurobiological stress research continues to be a driving force for scientific progress in gastroenterology and related clinical areas, inspiring translational research from animal models to clinical applications, while highlighting some areas that remain incompletely understood, such as the roles of sex/gender and gut microbiota in health and disease. Future directions of research should include not only the genetics of the stress response and resilience but also epigenetic contributions.
      PubDate: 2017-12-19T11:09:56Z
      DOI: 10.12688/f1000research.12435.1
      Issue No: Vol. 6 (2017)
  • Recent advances in pharmacological management of urinary incontinence
           [version 1; referees: 2 approved]

    • Authors: Bronagh McDonnell, Lori Ann Birder
      Abstract: Lower urinary tract symptoms—in particular, storage disorders (for example, urinary incontinence) as well as bladder underactivity—are major health-related problems that increase with age. Yet lower urinary tract symptoms remain under-diagnosed and poorly managed, and incontinence has been cited as the major reason for institutionalization in elderly populations and is one of the most common conditions in primary care practice. Although lifestyle and behavior therapy has been used as a useful treatment regimen for urge incontinence, medications (often used as adjunct) can provide additional benefit. This review will include current therapies used for treatment of urinary incontinence.
      PubDate: 2017-12-19T10:49:57Z
      DOI: 10.12688/f1000research.12593.1
      Issue No: Vol. 6 (2017)
  • Unexpected results in Chernozem soil respiration while measuring the
           effect of a bio-fertilizer on soil microbial activity [version 2;
           referees: 2 approved]

    • Authors: Gabriela Bautista, Bence Mátyás, Isabel Carpio, Richard Vilches, Karina Pazmino
      Abstract: The number of studies investigating the effect of bio-fertilizers is increasing because of their importance in sustainable agriculture and environmental quality. In our experiments, we measured the effect of different fertilizers on soil respiration. In the present study, we were looking for the cause of unexpected changes in CO2 values while examining Chernozem soil samples. We concluded that CO2 oxidizing microbes or methanotrophs may be present in the soil that periodically consume CO2 . This is unusual for a sample taken from the upper layer of well-ventilated Chernozem soil with optimal moisture content.
      PubDate: 2017-12-18T16:43:13Z
      DOI: 10.12688/f1000research.12936.2
      Issue No: Vol. 6 (2017)
  • Case Report: Laparoscopic hepatectomy in an elderly patient with major
           comorbidities [version 2; referees: 2 approved]

    • Authors: Georgios C. Sotiropoulos, Nikolaos Machairas, Ioannis D. Kostakis
      Abstract: Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to the higher rate of comorbidities and the reduced reserves. An 81-year-old male with hepatocellular carcinoma in the segment VI of the liver and several major cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our department for treatment. He underwent transarterial chemoembolization of the liver tumor and afterwards he underwent laparoscopic resection of the hepatic segment VI, with an uneventful postoperative course. This case indicates that laparoscopic liver resections could be applied even to elderly patients with major comorbidities after optimization of their medical status.
      PubDate: 2017-12-18T10:04:56Z
      DOI: 10.12688/f1000research.12078.2
      Issue No: Vol. 6 (2017)
  • Recent advances in pathophysiology of disseminated intravascular
           coagulation: the role of circulating histones and neutrophil extracellular
           traps [version 1; referees: 2 approved]

    • Authors: Yasir Alhamdi, Cheng-Hock Toh
      Abstract: Disseminated intravascular coagulation (DIC) is an acquired condition that develops as a complication of systemic and sustained cell injury in conditions such as sepsis and trauma. It represents major dysregulation and increased thrombin generation in vivo. A poor understanding and recognition of the complex interactions in the coagulation, fibrinolytic, inflammatory, and innate immune pathways have resulted in continued poor management and high mortality rates in DIC. This review focuses attention on significant recent advances in our understanding of DIC pathophysiology. In particular, circulating histones and neutrophil extracellular traps fulfil established criteria in DIC pathogenesis. Both are damaging to the vasculature and highly relevant to the cross talk between coagulation and inflammation processes, which can culminate in adverse clinical outcomes. These molecules have a strong potential to be novel biomarkers and therapeutic targets in DIC, which is still considered synonymous with ‘death is coming’.
      PubDate: 2017-12-18T09:38:46Z
      DOI: 10.12688/f1000research.12498.1
      Issue No: Vol. 6 (2017)
  • Advances in the understanding of IgM monoclonal gammopathy of undetermined
           significance [version 1; referees: 2 approved]

    • Authors: Jonas Paludo, Stephen M Ansell
      Abstract: Among monoclonal gammopathies of undetermined significance (MGUSs), the immunoglobulin M (IgM) MGUS subtype stands as a unique entity and plays a pivotal role as a pre-malignant condition for multiple B-cell non-Hodgkin lymphomas, most notably Waldenström macroglobulinemia (WM). A relationship between IgM MGUS and WM has been proposed for decades. However, insight regarding the pathobiology of these two conditions improved significantly in recent years, strengthening the hypothesis that WM and IgM MGUS are different stages of the same disease. Therefore, the understanding of IgM MGUS and that of WM are interconnected and advances in one will likely impact the other. Furthermore, IgM MGUS has been more commonly recognized as the underlying etiology of IgM-related disorders. In this review, we explore recent advances in the understanding of the pathobiology of IgM MGUS and WM and the treatment of common IgM-related disorders.
      PubDate: 2017-12-18T09:19:31Z
      DOI: 10.12688/f1000research.12880.1
      Issue No: Vol. 6 (2017)
  • Moms, babies, and bugs in immune development [version 1; referees: 2

    • Authors: Katie Alexander, Charles O. Elson
      Abstract: Bacteria and mammals have co-evolved with one another over millennia, and it has become impossible to interpret mucosal immunity without taking the microbiota into consideration. In fact, the primary role of the mucosal immune system is regulating homeostasis and the host relationship with the microbiota. Bacteria are no longer seen as simply invading pathogens, but rather a necessary component to one’s own immune response. On the one hand, the microbiota is a vital educator of immune cells and initiator of beneficial responses; but, on the other, dysbiosis of microbiota constituents are associated with inflammation and autoimmune disorders. In this review, we will consider recent advances in the understanding of how the microbiota influences host mucosal immunity, particularly the initial development of the immune response and its implications.
      PubDate: 2017-12-15T09:55:11Z
      DOI: 10.12688/f1000research.12182.1
      Issue No: Vol. 6 (2017)
  • Recent advances in understanding NRF2 as a druggable target: development
           of pro-electrophilic and non-covalent NRF2 activators to overcome systemic
           side effects of electrophilic drugs like dimethyl fumarate [version 1;
           referees: 2 approved]

    • Authors: Takumi Satoh, Stuart Lipton
      Abstract: Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera®. It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcriptional pathway that induces anti-oxidant and anti-inflammatory phase II enzymes to prevent chronic neurodegeneration. However, electrophiles such as DMF also produce severe systemic side effects, in part due to non-specific S-alkylation of cysteine thiols and resulting depletion of glutathione. This mini-review presents the present status and future strategy for NRF2 activators designed to avoid these side effects. Two modes of chemical reaction leading to NRF2 activation are considered here. The first mode is S-alkylation (covalent reaction) of thiols in Kelch-like ECH-associated protein 1 (KEAP1), which interacts with NRF2. The second mechanism involves non-covalent pharmacological inhibition of protein-protein interactions, in particular domain-specific interaction between NRF2 and KEAP1 or other repressor proteins involved in this transcriptional pathway. There have been significant advances in drug development using both of these mechanisms that can potentially avoid the systemic side effects of electrophilic compounds. In the first case concerning covalent reaction with KEAP1, monomethyl fumarate and monoethyl fumarate appear to represent safer derivatives of DMF. In a second approach, pro-electrophilic drugs, such as carnosic acid from the herb Rosmarinus officinalis, can be used as a safe pro-drug of an electrophilic compound. Concerning non-covalent activation of NRF2, drugs are being developed that interfere with the direct interaction of KEAP1-NRF2 or inhibit BTB domain and CNC homolog 1 (BACH1), which is a transcriptional repressor of the promoter where NRF2 binds.
      PubDate: 2017-12-14T14:54:05Z
      DOI: 10.12688/f1000research.12111.1
      Issue No: Vol. 6 (2017)
  • Case Report: Synchronous primary malignancy including the breast and
           endometrium [version 2; referees: 2 approved]

    • Authors: Elham-Sadat Bani-Mostafavi, Sepideh Tayebi, Maryam Tayebi, Fatemeh Montazer
      Abstract: Breast and endometrial cancer are the most common types of female cancers, but the incidence of both of these malignancies in a single patient is a rare event. Multiple primary malignancy has been increasingly reported over the past decade, and double primary cancer is considered as the most common type.  In this study, we present a 53-year-old woman with synchronous primary malignancy of breast and endometrium. This patient had a history of breast and endometrial cancer in her family. Mammography and chest CT of the patient revealed a mass in the right breast and left supraclavicular region. However, the patient did not want to initiate treatment. Subsequently, the patient returned with a chief complaint of persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient revealed a huge soft tissue mass in the pelvic cavity. She underwent hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded the full thickness of uterine wall. Since this type of malignancy is rare and several risk factors are associated with it, it is worth being considered by clinicians when making decisions about screening or strategy for prevention.
      PubDate: 2017-12-14T14:23:29Z
      DOI: 10.12688/f1000research.11971.2
      Issue No: Vol. 6 (2017)
  • How zebrafish research has helped in understanding thyroid diseases
           [version 1; referees: 2 approved]

    • Authors: Federica Marelli, Luca Persani
      Abstract: Next-generation sequencing technologies have revolutionized the identification of disease-causing genes, accelerating the discovery of new mutations and new candidate genes for thyroid diseases. To face this flow of novel genetic information, it is important to have suitable animal models to study the mechanisms regulating thyroid development and thyroid hormone availability and activity. Zebrafish (Danio rerio), with its rapid external embryonic development, has been extensively used in developmental biology. To date, almost all of the components of the zebrafish thyroid axis have been characterized and are structurally and functionally comparable with those of higher vertebrates. The availability of transgenic fluorescent zebrafish lines allows the real-time analysis of thyroid organogenesis and its alterations. Transient morpholino-knockdown is a solution to silence the expression of a gene of interest and promptly obtain insights on its contribution during the development of the zebrafish thyroid axis. The recently available tools for targeted stable gene knockout have further increased the value of zebrafish to the study of thyroid disease. All of the reported zebrafish models can also be used to screen small compounds and to test new drugs and may allow the establishment of experimental proof of concept to plan subsequent clinical trials.
      PubDate: 2017-12-14T12:04:45Z
      DOI: 10.12688/f1000research.12142.1
      Issue No: Vol. 6 (2017)
  • Tumor cell dormancy as an adaptive cell stress response mechanism [version
           1; referees: 4 approved]

    • Authors: Laura Vera-Ramirez, Kent W. Hunter
      Abstract: Metastases are responsible for most cancer-related deaths. The kinetics of tumor relapse is highly heterogeneous, ranging from recurrences shortly after diagnosis to years or even decades after the initial treatment. This subclinical period is known as tumor dormancy, in which residual disease remains in an undetectable state before finally appearing as an overtly proliferative metastasis. Despite recent advances in our understanding of the molecular mechanisms leading to tumor dormancy, it is still a poorly understood phase of cancer progression, which limits opportunities for the design of successful therapeutic interventions. The influence of the tumor microenvironment at the metastatic site and anti-metastatic immune responses have been shown to play a crucial role in the onset and maintenance of metastatic dormancy. However, there is still a significant gap in our understanding of how dormant cells remain viable in a quiescent state for long periods of time. Here, we review the latest experimental evidence shedding light on the biological processes that enable dormant tumor cells to endure the multiple stresses encountered at the metastatic site.
      PubDate: 2017-12-14T11:33:16Z
      DOI: 10.12688/f1000research.12174.1
      Issue No: Vol. 6 (2017)
  • Can circulating tumor DNA be used for direct and early stage cancer
           detection' [version 1; referees: 2 approved]

    • Authors: Eleftherios P Diamandis, Clare Fiala
      Abstract: In the August 16th issue of Science Translational Medicine, Phallen et al propose a method for early cancer diagnosis by using circulating tumor DNA (1). One major advance of this paper includes optimized sequencing of cell-free/circulating tumor DNA (ctDNA) without knowledge of tumor mutations. Evaluation of 200 patients with colorectal, breast, lung and ovarian cancer revealed mutations in ctDNA in approx. 60-70% of all patients, including stage 1 and stage 2 disease. If this data can be reproduced in asymptomatic individuals, they will likely have a major impact on early cancer detection and patient outcomes. In this commentary, we examine the feasibility of this approach for detecting small, asymptomatic tumors, based on previously published empirical data.
      PubDate: 2017-12-13T15:24:05Z
      DOI: 10.12688/f1000research.13440.1
      Issue No: Vol. 6 (2017)
  • Infectious pancreatic necrosis virus triggers antiviral immune response in
           rainbow trout red blood cells, despite not being infective [version 2;
           referees: 2 approved]

    • Authors: Ivan Nombela, Aurora Carrion, Sara Puente-Marin, Verónica Chico, Luis Mercado, Luis Perez, Julio Coll, Maria del Mar Ortega-Villaizan
      Abstract: Background: Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet. Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques. Results: IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genes ifn-1, pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line. Conclusions: Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs.
      PubDate: 2017-12-13T14:46:59Z
      DOI: 10.12688/f1000research.12994.2
      Issue No: Vol. 6 (2017)
  • Recent advances in understanding and managing T-cell lymphoma [version 1;
           referees: 2 approved]

    • Authors: Jun Ho Yi, Seok Jin Kim, Won Seog Kim
      Abstract: Owing to the rarity of peripheral T-cell lymphoma (PTCL) and the heterogeneity of subtypes, there are no compelling data to guide the therapeutic approaches for such patients. Over the years, there have been remarkable advances in molecular subtyping and treatment of PTCL, although there are still many areas to be explored. In this review, we summarize recent updates on the evolution of understanding and treatment for PTCL.
      PubDate: 2017-12-12T11:49:23Z
      DOI: 10.12688/f1000research.12573.1
      Issue No: Vol. 6 (2017)
  • Retract p < 0.005 and propose using JASP, instead [version 1; referees:
           2 approved]

    • Authors: Jose D. Perezgonzalez, M. Dolores Frías-Navarro
      Abstract: Seeking to address the lack of research reproducibility in science, including psychology and the life sciences, a pragmatic solution has been raised recently:  to use a stricter p < 0.005 standard for statistical significance when claiming evidence of new discoveries. Notwithstanding its potential impact, the proposal has motivated a large mass of authors to dispute it from different philosophical and methodological angles. This article reflects on the original argument and the consequent counterarguments, and concludes with a simpler and better-suited alternative that the authors of the proposal knew about and, perhaps, should have made from their Jeffresian perspective: to use a Bayes factors analysis in parallel (e.g., via JASP) in order to learn more about frequentist error statistics and about Bayesian prior and posterior beliefs without having to mix inconsistent research philosophies.
      PubDate: 2017-12-12T10:35:09Z
      DOI: 10.12688/f1000research.13389.1
      Issue No: Vol. 6 (2017)
  • Draft genome of tule elk Cervus canadensis nannodes [version 2; referees:
           2 approved]

    • Authors: Jessica E. Mizzi, Zachary T. Lounsberry, C. Titus Brown, Benjamin N. Sacks
      Abstract: This paper presents the first draft genome of the tule elk (Cervus elaphus nannodes), a subspecies native to California that underwent an extreme genetic bottleneck in the late 1800s.  The genome was generated from Illumina HiSeq 3000 whole genome sequencing of four individuals, resulting in the assembly of 2.395 billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp. This genome provides a resource to facilitate future genomic research on elk and other cervids.
      PubDate: 2017-12-11T14:26:19Z
      DOI: 10.12688/f1000research.12636.2
      Issue No: Vol. 6 (2017)
  • Initial study of three different pathogenic microorganisms by gas
           chromatography-mass spectrometry [version 2; referees: 2 approved, 1
           approved with reservations]

    • Authors: Najmeh Karami, Fateme Mirzajani, Hassan Rezadoost, Abdollah Karimi, Fatemeh Fallah, Alireza Ghassempour, Atusa Aliahmadi
      Abstract: Background: Diagnoses  of  respiratory  tract  infections  usually happen  in  the  late  phase  of  the  disease  and  usually  result  in  reduction  of  the  pathogen  load after broad-spectrum  antibiotic  therapy,  but  not  in eradication of the pathogen.  The  development  of a  non-invasive,  fast,  and  accurate  method  to  detect  pathogens  has  always  been  of  interest  to  researchers  and  clinicians  alike.  Previous studies have shown that bacteria produce organic gases.  The  current  study  aimed  to  identify  the  volatile  organic  compounds  (VOCs)  produced  by three  respiratory  tract  pathogens,  including  Staphylococcus  aureus,  Escherichia  coli  and  Candida  albicans. Methods: The  VOCs  produced  were identified by gas chromatography–mass spectrometry (GC-MS), with  prior  collection  of  microbial  volatile  compounds  using  solid  phase  microextraction  (SPME)  fiber.  The volatile compounds were collected by obtaining bacterial headspace samples. Results: Results  showed  that  these  three  organisms  have  various  VOCs,  which  were  analyzed  under  different  conditions.  By ignoring common VOCs, some species-specific VOCs could be detected.  The most important VOC of E. coli was Indole, also some important VOCs produced by S. aureus  were 2,3-Pentandione,  cis-Dihydro-α-terpinyl  acetate,  1-Decyne,  1,3-Heptadiene-3-yne,  2,5-dimethyl  Pyrazine,  Ethyl  butanoate  and  Cyclohexene,4-ethenyl  furthermore,  most  of  identified  compounds  by  C.  albicans are  alcohols. Conclusions: The  detection  of  VOCs  produced  by  infectious  agents  maybe  the  key  to  make   a  rapid  and  precise  diagnosis  of  infection,  but  more  comprehensive  studies  must  be  conducted  in this  regard.
      PubDate: 2017-12-11T14:23:30Z
      DOI: 10.12688/f1000research.12003.2
      Issue No: Vol. 6 (2017)
  • Health Technology Assessment capacity development in low- and
           middle-income countries: Experiences from the international units of HITAP
           and NICE [version 1; referees: 2 approved]

    • Authors: Sripen Tantivess, Kalipso Chalkidou, Nattha Tritasavit, Yot Teerawattananon
      Abstract: Health Technology Assessment (HTA) is policy research that aims to inform priority setting and resource allocation. HTA is increasingly recognized as a useful policy tool in low- and middle-income countries (LMICs), where there is a substantial need for evidence to guide Universal Health Coverage policies, such as benefit coverage, quality improvement interventions and quality standards, all of which aim at improving the efficiency and equity of the healthcare system. The Health Intervention and Technology Assessment Program (HITAP), Thailand, and the National Institute for Health and Care Excellence (NICE), UK, are national HTA organizations providing technical support to governments in LMICs to build up their priority setting capacity. This paper draws lessons from their capacity building programs in India, Colombia, Myanmar, the Philippines, and Vietnam. Such experiences suggest that it is not only technical capacity, for example analytical techniques for conducting economic evaluation, but also management, coordination and communication capacity that support the generation and use of HTA evidence in the respective settings. The learned lessons may help guide the development of HTA capacity in other LMICs.
      PubDate: 2017-12-11T10:06:37Z
      DOI: 10.12688/f1000research.13180.1
      Issue No: Vol. 6 (2017)
  • In silico analysis of natural compounds targeting structural and
           nonstructural proteins of chikungunya virus [version 2; referees: 2

    • Authors: Jaspreet Jain, Anchala Kumari, Pallavi Somvanshi, Abhinav Grover, Somnath Pai, Sujatha Sunil
      Abstract: Background: Chikungunya fever presents as a high-grade fever during its acute febrile phase and can be prolonged for months as chronic arthritis in affected individuals. Currently, there are no effective drugs or vaccines against this virus. The present study was undertaken to evaluate protein-ligand interactions of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase library in order to identify potential inhibitors of CHIKV. Methods: Virtual screening of the natural compound library against four non-structural and five structural proteins of CHIKV was performed. Homology models of the viral proteins with unknown structures were created and energy minimized by molecular dynamic simulations. Molecular docking was performed to identify the potential inhibitors for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity parameters for the potential inhibitors were predicted for further prioritization of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O-gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two (Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one (Arjungenin) with the E3. Conclusion: The compounds identified show promise as potential antivirals, but further in vitro studies are required to test their efficacy against CHIKV.
      PubDate: 2017-12-08T10:19:03Z
      DOI: 10.12688/f1000research.12301.2
      Issue No: Vol. 6 (2017)
  • Developing data interoperability using standards: A wheat community use
           case [version 2; referees: 2 approved]

    • Authors: Esther Dzale Yeumo, Michael Alaux, Elizabeth Arnaud, Sophie Aubin, Ute Baumann, Patrice Buche, Laurel Cooper, Hanna Ćwiek-Kupczyńska, Robert P. Davey, Richard Allan Fulss, Clement Jonquet, Marie-Angélique Laporte, Pierre Larmande, Cyril Pommier, Vassilis Protonotarios, Carmen Reverte, Rosemary Shrestha, Imma Subirats, Aravind Venkatesan, Alex Whan, Hadi Quesneville
      Abstract: In this article, we present a joint effort of the wheat research community, along with data and ontology experts, to develop wheat data interoperability guidelines. Interoperability is the ability of two or more systems and devices to cooperate and exchange data, and interpret that shared information. Interoperability is a growing concern to the wheat scientific community, and agriculture in general, as the need to interpret the deluge of data obtained through high-throughput technologies grows. Agreeing on common data formats, metadata, and vocabulary standards is an important step to obtain the required data interoperability level in order to add value by encouraging data sharing, and subsequently facilitate the extraction of new information from existing and new datasets. During a period of more than 18 months, the RDA Wheat Data Interoperability Working Group (WDI-WG) surveyed the wheat research community about the use of data standards, then discussed and selected a set of recommendations based on consensual criteria. The recommendations promote standards for data types identified by the wheat research community as the most important for the coming years: nucleotide sequence variants, genome annotations, phenotypes, germplasm data, gene expression experiments, and physical maps. For each of these data types, the guidelines recommend best practices in terms of use of data formats, metadata standards and ontologies. In addition to the best practices, the guidelines provide examples of tools and implementations that are likely to facilitate the adoption of the recommendations. To maximize the adoption of the recommendations, the WDI-WG used a community-driven approach that involved the wheat research community from the start, took into account their needs and practices, and provided them with a framework to keep the recommendations up to date. We also report this approach’s potential to be generalizable to other (agricultural) domains.
      PubDate: 2017-12-06T15:46:01Z
      DOI: 10.12688/f1000research.12234.2
      Issue No: Vol. 6 (2017)
  • Using to generate and annotate workbench tool descriptions
           [version 1; referees: 2 approved]

    • Authors: Kenzo-Hugo Hillion, Ivan Kuzmin, Anton Khodak, Eric Rasche, Michael Crusoe, Hedi Peterson, Jon Ison, Hervé Ménager
      Abstract: Workbench and workflow systems such as Galaxy, Taverna, Chipster, or Common Workflow Language (CWL)-based frameworks, facilitate the access to bioinformatics tools in a user-friendly, scalable and reproducible way. Still, the integration of tools in such environments remains a cumbersome, time consuming and error-prone process. A major consequence is the incomplete or outdated description of tools that are often missing important information, including parameters and metadata such as publication or links to documentation. ToolDog (Tool DescriptiOn Generator) facilitates the integration of tools - which have been registered in the ELIXIR tools registry ( - into workbench environments by generating tool description templates. ToolDog includes two modules. The first module analyses the source code of the bioinformatics software with language-specific plugins, and generates a skeleton for a Galaxy XML or CWL tool description. The second module is dedicated to the enrichment of the generated tool description, using metadata provided by This last module can also be used on its own to complete or correct existing tool descriptions with missing metadata.
      PubDate: 2017-11-30T14:06:45Z
      DOI: 10.12688/f1000research.12974.1
      Issue No: Vol. 6 (2017)
  • Out-of-pocket health expenditure and fairness in utilization of health
           care facilities in Cambodia in 2005 and 2010 [version 1; referees: 2

    • Authors: Koustuv Dalal, Olatunde Aremu, Gainel Ussatayeva, Animesh Biswas
      Abstract: Background: Out-of-pocket (OOP) payments for health care are highly pervasive in several low-and-middle income countries. The Cambodian health system has envisaged massive repositioning of various health care financing to ensure equitable access to health care. This analysis examines catastrophic, economic, as well as fairness, impacts of OOP health care payments on households in Cambodia over time. Methods: Data from two waves of a nationally representative household survey conducted in Cambodia (CDHS Surveys 2005 and 2010) were utilized. Healthcare utilizations based on economic status were compared during 2005 and 2010. Variables of interests were i) where care was sought and the instances of treatments, i.e. was treatment sought the first, second or third time; (ii) the mode of payment for treatment of the respondent or for any household member due to sickness or injury in the last 30 days prior to the survey period. Lorenz curves were applied to assess the degree of distribution of inequality in OOP expenditures between different income brackets. Results: The findings revealed that there was inequality and unfairness in health care payments, and catastrophic spending is more common among the poor in Cambodia. The majority of people from poorer households experienced economic hardship and have taken to catastrophic health care spending through sales of personal possessions.  Conclusion: Based on the findings from this analysis, more attention is needed on effective financial protection for Cambodians to promote fairness. The government should increase spending on services being provided at public health care facilities to reduce ever increasing reliance on private sector providers. These approaches would go a long way to reduce the economic burden of care utilization among the poorest.
      PubDate: 2017-11-29T14:54:30Z
      DOI: 10.12688/f1000research.12801.1
      Issue No: Vol. 6 (2017)
  • Differential methylation analysis of reduced representation bisulfite
           sequencing experiments using edgeR [version 1; referees: 2 approved, 1
           approved with reservations]

    • Authors: Yunshun Chen, Bhupinder Pal, Jane E. Visvader, Gordon K. Smyth
      Abstract: Studies in epigenetics have shown that DNA methylation is a key factor in regulating gene expression. Aberrant DNA methylation is often associated with DNA instability, which could lead to development of diseases such as cancer. DNA methylation typically occurs in CpG context. When located in a gene promoter, DNA methylation often acts to repress transcription and gene expression. The most commonly used technology of studying DNA methylation is bisulfite sequencing (BS-seq), which can be used to measure genomewide methylation levels on the single-nucleotide scale. Notably, BS-seq can also be combined with enrichment strategies, such as reduced representation bisulfite sequencing (RRBS), to target CpG-rich regions in order to save per-sample costs. A typical DNA methylation analysis involves identifying differentially methylated regions (DMRs) between different experimental conditions. Many statistical methods have been developed for finding DMRs in BS-seq data. In this workflow, we propose a novel approach of detecting DMRs using edgeR. By providing a complete analysis of RRBS profiles of epithelial populations in the mouse mammary gland, we will demonstrate that differential methylation analyses can be fit into the existing pipelines specifically designed for RNA-seq differential expression studies. In addition, the edgeR generalized linear model framework offers great flexibilities for complex experimental design, while still accounting for the biological variability. The analysis approach illustrated in this article can be applied to any BS-seq data that includes some replication, but it is especially appropriate for RRBS data with small numbers of biological replicates.
      PubDate: 2017-11-28T14:30:43Z
      DOI: 10.12688/f1000research.13196.1
      Issue No: Vol. 6 (2017)
  • Funding knowledgebases: Towards a sustainable funding model for the
           UniProt use case [version 1; referees: 2 approved]

    • Authors: Chiara Gabella, Christine Durinx, Ron Appel
      Abstract: Millions of life scientists across the world rely on bioinformatics data resources for their research projects. Data resources can be very expensive, especially those with a high added value as the expert-curated knowledgebases. Despite the increasing need for such highly accurate and reliable sources of scientific information, most of them do not have secured funding over the near future and often depend on short-term grants that are much shorter than their planning horizon. Additionally, they are often evaluated as research projects rather than as research infrastructure components. In this work, twelve funding models for data resources are described and applied on the case study of the Universal Protein Resource (UniProt), a key resource for protein sequences and functional information knowledge. We show that most of the models present inconsistencies with open access or equity policies, and that while some models do not allow to cover the total costs, they could potentially be used as a complementary income source. We propose the Infrastructure Model as a sustainable and equitable model for all core data resources in the life sciences. With this model, funding agencies would set aside a fixed percentage of their research grant volumes, which would subsequently be redistributed to core data resources according to well-defined selection criteria. This model, compatible with the principles of open science, is in agreement with several international initiatives such as the Human Frontiers Science Program Organisation (HFSPO) and the OECD Global Science Forum (GSF) project. Here, we have estimated that less than 1% of the total amount dedicated to research grants in the life sciences would be sufficient to cover the costs of the core data resources worldwide, including both knowledgebases and deposition databases.
      PubDate: 2017-11-27T14:09:49Z
      DOI: 10.12688/f1000research.12989.1
      Issue No: Vol. 6 (2017)
  • Easy and efficient ensemble gene set testing with EGSEA [version 1;
           referees: 1 approved, 3 approved with reservations]

    • Authors: Monther Alhamdoosh, Charity W. Law, Luyi Tian, Julie M. Sheridan, Milica Ng, Matthew E. Ritchie
      Abstract: Gene set enrichment analysis is a popular approach for prioritising the biological processes perturbed in genomic datasets. The Bioconductor project hosts over 80 software packages capable of gene set analysis. Most of these packages search for enriched signatures amongst differentially regulated genes to reveal higher level biological themes that may be missed when focusing only on evidence from individual genes. With so many different methods on offer, choosing the best algorithm and visualization approach can be challenging. The EGSEA package solves this problem by combining results from up to 12 prominent gene set testing algorithms to obtain a consensus ranking of biologically relevant results.This workflow demonstrates how EGSEA can extend limma-based differential expression analyses for RNA-seq and microarray data using experiments that profile 3 distinct cell populations important for studying the origins of breast cancer. Following data normalization and set-up of an appropriate linear model for differential expression analysis, EGSEA builds gene signature specific indexes that link a wide range of mouse or human gene set collections obtained from MSigDB, GeneSetDB and KEGG to the gene expression data being investigated. EGSEA is then configured and the ensemble enrichment analysis run, returning an object that can be queried using several S4 methods for ranking gene sets and visualizing results via heatmaps, KEGG pathway views, GO graphs, scatter plots and bar plots. Finally, an HTML report that combines these displays can fast-track the sharing of results with collaborators, and thus expedite downstream biological validation. EGSEA is simple to use and can be easily integrated with existing gene expression analysis pipelines for both human and mouse data.
      PubDate: 2017-11-14T11:56:34Z
      DOI: 10.12688/f1000research.12544.1
      Issue No: Vol. 6 (2017)
  • Optimal cutoff for the evaluation of insulin resistance through
           triglyceride-glucose index: A cross-sectional study in a Venezuelan
           population [version 2; referees: 2 approved]

    • Authors: Juan Salazar, Valmore Bermúdez, María Calvo, Luis Carlos Olivar, Eliana Luzardo, Carla Navarro, Heysa Mencia, María Martínez, José Rivas-Ríos, Sandra Wilches-Durán, Marcos Cerda, Modesto Graterol, Rosemily Graterol, Carlos Garicano, Juan Hernández, Joselyn Rojas
      Abstract: Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical and epidemiological research. However, the most widely used methods are difficult to apply to populations with low incomes. The triglyceride-glucose index (TGI) emerges as an alternative to use in daily clinical practice. Therefore the objective of this study was to determine an optimal cutoff point for the TGI in an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross-sectional study with random and multi-stage sampling. For this analysis, 2004 individuals of both genders ≥18 years old with basal insulin determination and triglycerides < 500 mg/dl were evaluated.. A reference population was selected according to clinical and metabolic criteria to plot ROC Curves specific for gender and age groups to determine the optimal cutoff point according to sensitivity and specificity.The TGI was calculated according to the equation: ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The TGI in the general population was 4.6±0.3 (male: 4.66±0.34 vs. female: 4.56±0.33, p=8.93x10-10). The optimal cutoff point was 4.49, with a sensitivity of 82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no significant differences in the predictive capacity of the index when evaluated according to gender and age groups. Those individuals with TGI≥4.5 had higher HOMA2-IR averages than those with TGI
      PubDate: 2017-10-20T11:18:30Z
      DOI: 10.12688/f1000research.12170.2
      Issue No: Vol. 6 (2017)
  • Comparison of school based and supplemental vaccination strategies in the
           delivery of vaccines to 5-19 year olds in Africa - a systematic review
           [version 1; referees: 2 approved]

    • Authors: Eposi C. Haddison, Leila H. Abdullahi, Rudzani Muloiwa, Gregory D. Hussey, Benjamin M. Kagina
      Abstract: Background: Some vaccine preventable diseases (VPDs) still remain a public health burden in many African countries. The occurrence of VPDs in all age groups has led to the realization of the need to extend routine immunisation services to school age children, adolescents and adults. Supplemental immunisation activities (SIAs) and school based vaccinations (SBVs) are common strategies used to complement the expanded programme on immunisation (EPI). This review aimed to assess the effectiveness of SIAs compared to SBVs in the administration of vaccines to 5-19 year olds in Africa. Methods: Systematic review methods were used to address our study aim. Several electronic databases were searched up to March 30, 2017 for primary studies investigating the delivery of vaccines via SIAs or SBVs to 5-19 year olds. This search was complemented by browsing reference lists of potential studies obtained from search outputs. Outcomes considered for inclusion were: vaccination coverage, costs of the strategy or its effect on routine immunisation services. Results: Out of the 4938 studies identified, 31 studies met the review inclusion criteria. Both SIAs and SBVs showed high vaccination coverage. However, the SIAs reported higher coverage than SBVs: 91% (95% CI: 84%, 98%) versus 75% (95% CI: 67%, 83%). In most settings, SBVs were reported to be more expensive than SIAs. The SIAs were found to negatively affect routine immunisation services. Conclusions: Both SIAs and SBVs are routinely used to complement the EPI in the delivery of vaccines in Africa. In settings where school enrolment is suboptimal, as is the case in many African countries, our results show SIAs may be more effective in reaching school age children and adolescents than SBVs. Our results re-iterate the importance of evaluating systematic evidence to best inform African authorities on the optimal vaccine delivery strategies targeting school age children and adolescents.
      PubDate: 2017-10-13T11:10:58Z
      DOI: 10.12688/f1000research.12804.1
      Issue No: Vol. 6 (2017)
  • A method to estimate the number of neurons supporting visual orientation
           discrimination in primates [version 1; referees: 2 approved]

    • Authors: Ruben Coen-Cagli, Ingmar Kanitscheider, Alexandre Pouget
      Abstract: In this method article, we show how to estimate of the number of retinal ganglion cells (RGC), and the number of lateral genicular nucleus (LGN) and primary visual cortex (V1) neurons involved in visual orientation discrimination tasks. We reported the results of this calculation in Kanitscheider et al. (2015), where we were interested in comparing the number of neurons in the visual periphery versus visual cortex for a specific experiment. This calculation allows estimation of the information content at different stages of the visual pathway, which can be used to assess the efficiency of the computations performed. As these numbers are generally not readily available but may be useful to other researchers, we explain here in detail how we obtained them. The calculation is straightforward, and simply requires combining anatomical and physiological information about the macaque visual pathway. Similar information could be used to repeat the calculation for other species or modalities.
      PubDate: 2017-09-26T13:26:17Z
      DOI: 10.12688/f1000research.12398.1
      Issue No: Vol. 6 (2017)
  • On the primacy and irreducible nature of first-person versus third-person
           information [version 3; referees: 1 approved, 2 approved with

    • Authors: Patrizio E. Tressoldi, Enrico Facco, Daniela Lucangeli
      Abstract: In this essay, we will support the claim that at the current level of scientific advancement a) some first-person accounts cannot be reduced to their third-person neural and psychophysiological correlates and b) that these first-person accounts are the only information to reckon when it is necessary to analyse qualia contents. Consequently, for many phenomena, first-person accounts are the only reliable source of information available and the knowledge of their neural and psychophysical correlates don’t offer any additional information about them.
      PubDate: 2017-05-31T09:46:52Z
      DOI: 10.12688/f1000research.10752.3
      Issue No: Vol. 6 (2017)
  • Crystallization and preliminary X-ray diffraction analysis of YejM from
           Salmonella typhimurium: an essential inner membrane protein involved in
           outer membrane directed cardiolipin transport [version 2; referees: 2

    • Authors: Uma Gabale, Gene Qian, Elaina Roach, Susanne Ressl
      Abstract: Salmonella  typhimurium is responsible for over 35% of all foodborne illness related hospitalizations in the United States. This Gram-negative bacterium possesses an inner and an outer membrane (OM), the latter allowing its survival and replication within host tissues. During infection, OM is remodeled by transport of glycerophospholipids across the periplasm and into the OM. Increased levels of cardiolipin in the OM were observed upon PhoPQ activation and led to the discovery of YejM; an inner membrane protein essential for cell growth involved in cardiolipin binding and transport to the OM. Here we report how YejM was engineered to facilitate crystal growth and X-ray diffraction analysis. Successful structure determination of YejM will help us understand how they interact and how YejM facilitates cardiolipin transport to the OM. Ultimately, yejm, being an essential gene, may lead to new drug targets inhibiting the pathogenic properties of S. typhimurium.
      PubDate: 2017-12-11T14:21:00Z
      DOI: 10.12688/f1000research.8647.2
      Issue No: Vol. 5 (2017)
  • Predicted protein interactions of IFITMs may shed light on mechanisms of
           Zika virus-induced microcephaly and host invasion [version 2; referees: 2
           approved, 1 approved with reservations, 1 not approved]

    • Authors: Madhavi K. Ganapathiraju, Kalyani B. Karunakaran, Josefina Correa-Menéndez
      Abstract: After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a significant increase in the reported cases of microcephaly was observed. Microcephaly is a neurological condition in which the infant’s head is significantly smaller with complications in brain development. Recently, two small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown to repress members of the flaviviridae family which includes ZIKV. However, the exact mechanisms leading to the inhibition of the virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known protein-protein interactions (PPIs) collected from publicly available databases and novel PPIs predicted using the High-confidence Protein-Protein Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway associations of the interacting proteins, and found that there are several immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper cells, crosstalk between dendritic cells and natural killer cells), neuronal pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton signaling) and developmental pathways (neural tube closure, embryonic skeletal system development) that are associated with these interactors. Our novel PPIs associate cilia dysfunction in ependymal cells to microcephaly, and may also shed light on potential targets of ZIKV for host invasion by immunosuppression and cytoskeletal rearrangements. These results could help direct future research in elucidating the mechanisms underlying host defense to ZIKV and other flaviviruses.
      PubDate: 2017-11-21T14:15:55Z
      DOI: 10.12688/f1000research.9364.2
      Issue No: Vol. 5 (2017)
  • Quantification of polysaccharides fixed to Gram stained slides using
           lactophenol cotton blue and digital image processing [version 5; referees:
           2 approved, 1 approved with reservations]

    • Authors: Bryan Ericksen
      Abstract: Dark blue rings and circles emerged when the non-specific polysaccharide stain lactophenol cotton blue was added to Gram stained slides. The dark blue staining is attributable to the presence of capsular polysaccharides and bacterial slime associated with clumps of Gram-negative bacteria.  Since all bacterial cells are glycosylated and concentrate polysaccharides from the media, the majority of cells stain light blue. The contrast between dark and light staining is sufficient to enable a digital image processing thresholding technique to be quantitative with little background noise. Prior to the addition of lactophenol cotton blue, the Gram-stained slides appeared unremarkable, lacking ubiquitous clumps or stained polysaccharides.  Adding lactophenol cotton blue to Gram stained slides is a quick and inexpensive way to screen cell cultures for bacterial slime, clumps and biofilms that are invisible using the Gram stain alone.
      PubDate: 2017-12-06T14:36:05Z
      DOI: 10.12688/f1000research.5779.5
      Issue No: Vol. 4 (2017)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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