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Journal Cover F1000Research
  [SJR: 0.219]   [H-I: 3]   [4 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2046-1402
   Published by Faculty of 1000 Homepage  [1 journal]
  • Toxic epidermal necrolysis [version 1; referees: 3 approved]

    • Authors: Wolfram Hoetzenecker, Tarun Mehra, Ieva Saulite, Martin Glatz, Peter Schmid-Grendelmeier, Emmanuella Guenova, Antonio Cozzio, Lars E. French
      Abstract: Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care.
      PubDate: 2016-05-20T14:51:15Z
      DOI: 10.12688/f1000research.7574.1
      Issue No: Vol. 5 (2016)
  • Recent advances in microscopic techniques for visualizing leukocytes in
           vivo [version 1; referees: 3 approved]

    • Authors: Rohit Jain, Shweta Tikoo, Wolfgang Weninger
      Abstract: Leukocytes are inherently motile and interactive cells. Recent advances in intravital microscopy approaches have enabled a new vista of their behavior within intact tissues in real time. This brief review summarizes the developments enabling the tracking of immune responses in vivo.
      PubDate: 2016-05-19T14:10:35Z
      DOI: 10.12688/f1000research.8127.1
      Issue No: Vol. 5 (2016)
  • The potential of plants as a system for the development and production of
           human biologics [version 1; referees: 3 approved]

    • Authors: Qiang Chen, Keith R. Davis
      Abstract: The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology.
      PubDate: 2016-05-19T10:10:00Z
      Issue No: Vol. 5 (2016)
  • Upper extremity nerve block: how can benefit, duration, and safety be
           improved' An update [version 1; referees: 3 approved]

    • Abstract: Upper extremity blocks are useful as both sole anaesthesia and/or a supplement to general anaesthesia and they further provide effective postoperative analgesia, reducing the need for opioid analgesics. There is without doubt a renewed interest among anaesthesiologists in the interscalene, supraclavicular, infraclavicular, and axillary plexus blocks with the increasing use of ultrasound guidance. The ultrasound-guided technique visualising the needle tip and solution injected reduces the risk of side effects, accidental intravascular injection, and possibly also trauma to surrounding tissues. The ultrasound technique has also reduced the volume needed in order to gain effective block. Still, single-shot plexus block, although it produces effective anaesthesia, has a limited duration of postoperative analgesia and a number of adjuncts have been tested in order to prolong analgesia duration. The addition of steroids, midazolam, clonidine, dexmedetomidine, and buprenorphine has been studied, all being off-label when administered by perineural injection, and the potential neurotoxicity needs further study. The use of perineural catheters is an effective option to improve and prolong the postoperative analgesic effect. Upper extremity plexus blocks have an obvious place as a sole anaesthetic technique or as a powerful complement to general anaesthesia, reducing the need for analgesics and hypnotics intraoperatively, and provide effective early postoperative pain relief. Continuous perineural infusion is an effective option to prolong the effects and improve postoperative quality.
      PubDate: 2016-05-18T15:38:11Z
      DOI: 10.12688/f1000research.7292.1
      Issue No: Vol. 5 (2016)
  • Network science for the identification of novel therapeutic targets in
           epilepsy [version 1; referees: 2 approved]

    • Authors: Rod C. Scott
      Abstract: The quality of life of children with epilepsy is a function of seizures and associated cognitive and behavioral comorbidities. Current treatments are not successful at stopping seizures in approximately 30% of patients despite the introduction of multiple new antiepileptic drugs over the last decade. In addition, modification of seizures has only a modest impact on the comorbidities. Therefore, novel approaches to identify therapeutic targets that improve seizures and comorbidities are urgently required. The potential of network science as applied to genetic, local neural network, and global brain data is reviewed. Several examples of possible new therapeutic approaches defined using novel network tools are highlighted. Further study to translate the findings into clinical practice is now required.
      PubDate: 2016-05-16T15:41:02Z
      DOI: 10.12688/f1000research.8214.1
      Issue No: Vol. 5 (2016)
  • Intravital imaging reveals new ancillary mechanisms co-opted by cancer
           cells to drive tumor progression [version 1; referees: 2 approved]

    • Authors: Claire Vennin, David Herrmann, Morghan C. Lucas, Paul Timpson
      Abstract: Intravital imaging is providing new insights into the dynamics of tumor progression in native tissues and has started to reveal the layers of complexity found in cancer. Recent advances in intravital imaging have allowed us to look deeper into cancer behavior and to dissect the interactions between tumor cells and the ancillary host niche that promote cancer development. In this review, we provide an insight into the latest advances in cancer biology achieved by intravital imaging, focusing on recently discovered mechanisms by which tumor cells manipulate normal tissue to facilitate disease progression.
      PubDate: 2016-05-16T15:27:35Z
      DOI: 10.12688/f1000research.8090.1
      Issue No: Vol. 5 (2016)
  • Substance use during pregnancy [version 1; referees: 2 approved]

    • Authors: Ariadna Forray
      Abstract: Prenatal substance use is a critical public health concern that is linked with several harmful maternal and fetal consequences. The most frequently used substance in pregnancy is tobacco, followed by alcohol, cannabis and other illicit substances. Unfortunately, polysubstance use in pregnancy is common, as well as psychiatric comorbidity, environmental stressors, and limited and disrupted parental care, all of which can compound deleterious maternal and fetal outcomes. There are few existing treatments for prenatal substance use and these mainly comprise behavioral and psychosocial interventions. Contingency management has been shown to be the most efficacious of these. The purpose of this review is to examine the recent literature on the prenatal use of tobacco, alcohol, cannabis, stimulants, and opioids, including the effects of these on maternal and fetal health and the current therapeutic options.
      PubDate: 2016-05-13T14:55:47Z
      DOI: 10.12688/f1000research.7645.1
      Issue No: Vol. 5 (2016)
  • Central control of body temperature [version 1; referees: 3 approved]

    • Authors: Shaun F. Morrison
      Abstract: Central neural circuits orchestrate the behavioral and autonomic repertoire that maintains body temperature during environmental temperature challenges and alters body temperature during the inflammatory response and behavioral states and in response to declining energy homeostasis. This review summarizes the central nervous system circuit mechanisms controlling the principal thermoeffectors for body temperature regulation: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for thermogenesis. The activation of these thermoeffectors is regulated by parallel but distinct efferent pathways within the central nervous system that share a common peripheral thermal sensory input. The model for the neural circuit mechanism underlying central thermoregulatory control provides a useful platform for further understanding of the functional organization of central thermoregulation, for elucidating the hypothalamic circuitry and neurotransmitters involved in body temperature regulation, and for the discovery of novel therapeutic approaches to modulating body temperature and energy homeostasis.
      PubDate: 2016-05-12T14:13:39Z
      DOI: 10.12688/f1000research.7958.1
      Issue No: Vol. 5 (2016)
  • Molecular pathogenesis of hepatocellular carcinoma and impact of
           therapeutic advances [version 1; referees: 4 approved]

    • Authors: Renumathy Dhanasekaran, Salome Bandoh, Lewis R. Roberts
      Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development.
      PubDate: 2016-05-12T14:04:14Z
      DOI: 10.12688/f1000research.6946.1
      Issue No: Vol. 5 (2016)
  • Cell cycle regulated transcription: from yeast to cancer [version 1;
           referees: 2 approved]

    • Authors: Christopher J. McInerny
      Abstract: Recent studies have revealed exciting new functions for forkhead transcription factors in cell proliferation and development. Cell proliferation is a fundamental process controlled by multiple overlapping mechanisms, and the control of gene expression plays a major role in the orderly and timely division of cells. This occurs through transcription factors regulating the expression of groups of genes at particular phases of the cell division cycle. In this way, the encoded gene products are present when they are required. This review outlines recent advances in our understanding of this process in yeast model systems and describes how this knowledge has informed analysis in more developmentally complex eukaryotes, particularly where it is relevant to human disease.
      PubDate: 2016-05-12T11:22:34Z
      DOI: 10.12688/f1000research.8111.1
      Issue No: Vol. 5 (2016)
  • Intracerebral haemorrhage in Down syndrome: protected or predisposed'
           [version 1; referees: 2 approved]

    • Abstract: Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer’s disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein (APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called ‘dup-APP’, which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight.
      PubDate: 2016-05-12T11:07:49Z
      DOI: 10.12688/f1000research.7819.1
      Issue No: Vol. 5 (2016)
  • Hox genes and evolution [version 1; referees: 3 approved]

    • Authors: Steven M. Hrycaj, Deneen M. Wellik
      Abstract: Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan.
      PubDate: 2016-05-10T10:37:32Z
      DOI: 10.12688/f1000research.7663.1
      Issue No: Vol. 5 (2016)
  • Current clinical immunotherapeutic approaches for head and neck cancer
           [version 1; referees: 2 approved]

    • Authors: Carolina Soto Chervin, Bruce Brockstein
      Abstract: It was estimated that 59,340 new cases of head and neck cancer would be diagnosed in the US alone in 2015 and that 12,290 deaths would be attributed to the disease. Local and regional recurrences may be treated with chemotherapy and radiation; however, metastatic head and neck cancer is fatal and is treated with chemotherapy for palliation. Recent successful treatment of a variety of solid and hematological malignancies by immunotherapeutic approaches (i.e. harnessing the body’s own immune system to combat disease) has added a fourth therapeutic option for the treatment of cancer. This commentary will review the status of immunotherapies in clinical development for the specific treatment of head and neck cancer.
      PubDate: 2016-05-05T14:37:26Z
      DOI: 10.12688/f1000research.7762.1
      Issue No: Vol. 5 (2016)
  • Recent advances in echocardiography: strain and strain rate imaging
           [version 1; referees: 3 approved]

    • Authors: Oana Mirea, Jurgen Duchenne, Jens-Uwe Voigt
      Abstract: Deformation imaging by echocardiography is a well-established research tool which has been gaining interest from clinical cardiologists since the introduction of speckle tracking. Post-processing of echo images to analyze deformation has become readily available at the fingertips of the user. New parameters such as global longitudinal strain have been shown to provide added diagnostic value, and ongoing efforts of the imaging societies and industry aimed at harmonizing methods will improve the technique further. This review focuses on recent advances in the field of echocardiographic strain and strain rate imaging, and provides an overview on its current and potential future clinical applications.
      PubDate: 2016-04-29T15:34:08Z
      DOI: 10.12688/f1000research.7228.1
      Issue No: Vol. 5 (2016)
  • Geroscience approaches to increase healthspan and slow aging [version 1;
           referees: 2 approved]

    • Authors: Simon Melov
      Abstract: For decades, researchers in the biology of aging have focused on defining mechanisms that modulate aging by primarily studying a single metric, sometimes described as the “gold standard” lifespan. Increasingly, geroscience research is turning towards defining functional domains of aging such as the cardiovascular system, skeletal integrity, and metabolic health as being a more direct route to understand why tissues decline in function with age. Each model used in aging research has strengths and weaknesses, yet we know surprisingly little about how critical tissues decline in health with increasing age. Here I discuss popular model systems used in geroscience research and their utility as possible tools in preclinical studies in aging.
      PubDate: 2016-04-29T14:28:50Z
      DOI: 10.12688/f1000research.7583.1
      Issue No: Vol. 5 (2016)
  • Rho, ROCK and actomyosin contractility in metastasis as drug targets
           [version 1; referees: 2 approved]

    • Authors: Irene Rodriguez-Hernandez, Gaia Cantelli, Fanshawe Bruce, Victoria Sanz-Moreno
      Abstract: Metastasis is the spread of cancer cells around the body and the cause of the majority of cancer deaths. Metastasis is a very complex process in which cancer cells need to dramatically modify their cytoskeleton and cope with different environments to successfully colonize a secondary organ. In this review, we discuss recent findings pointing at Rho-ROCK or actomyosin force (or both) as major drivers of many of the steps required for metastatic success. We propose that these are important drug targets that need to be considered in the clinic to palliate metastatic disease.
      PubDate: 2016-04-29T14:11:02Z
      DOI: 10.12688/f1000research.7909.1
      Issue No: Vol. 5 (2016)
  • Recent advances in large-scale protein interactome mapping [version 1;
           referees: 3 approved]

    • Authors: Virja Mehta, Laura Trinkle-Mulcahy
      Abstract: Protein-protein interactions (PPIs) underlie most, if not all, cellular functions. The comprehensive mapping of these complex networks of stable and transient associations thus remains a key goal, both for systems biology-based initiatives (where it can be combined with other ‘omics’ data to gain a better understanding of functional pathways and networks) and for focused biological studies. Despite the significant challenges of such an undertaking, major strides have been made over the past few years. They include improvements in the computation prediction of PPIs and the literature curation of low-throughput studies of specific protein complexes, but also an increase in the deposition of high-quality data from non-biased high-throughput experimental PPI mapping strategies into publicly available databases.
      PubDate: 2016-04-29T13:58:02Z
      DOI: 10.12688/f1000research.7629.1
      Issue No: Vol. 5 (2016)
  • Irritable bowel syndrome: new insights into symptom mechanisms and
           advances in treatment [version 1; referees: 2 approved]

    • Authors: Robin Spiller
      Abstract: Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.
      PubDate: 2016-04-29T13:03:57Z
      DOI: 10.12688/f1000research.7992.1
      Issue No: Vol. 5 (2016)
  • Kin and multilevel selection in social evolution: a never-ending
           controversy' [version 1; referees: 4 approved]

    • Abstract: Kin selection and multilevel selection are two major frameworks in evolutionary biology that aim at explaining the evolution of social behaviors. However, the relationship between these two theories has been plagued by controversy for almost half a century and debates about their relevance and usefulness in explaining social evolution seem to rekindle at regular intervals. Here, we first provide a concise introduction into the kin selection and multilevel selection theories and shed light onto the roots of the controversy surrounding them. We then review two major aspects of the current debate: the presumed formal equivalency of the two theories and the question whether group selection can lead to group adaptation. We conclude by arguing that the two theories can offer complementary approaches to the study of social evolution: kin selection approaches usually focus on the identification of optimal phenotypes and thus on the endresult of a selection process, whereas multilevel selection approaches focus on the ongoing selection process itself. The two theories thus provide different perspectives that might be fruitfully combined to promote our understanding of the evolution in group-structured populations.
      PubDate: 2016-04-28T16:05:46Z
      DOI: 10.12688/f1000research.8018.1
      Issue No: Vol. 5 (2016)
  • Current techniques for visualizing RNA in cells [version 1; referees: 2

    • Authors: Lilith V.J.C. Mannack, Sebastian Eising, Andrea Rentmeister
      Abstract: Labeling RNA is of utmost interest, particularly in living cells, and thus RNA imaging is an emerging field. There are numerous methods relying on different concepts ranging from hybridization-based probes, over RNA-binding proteins to chemo-enzymatic modification of RNA. These methods have different benefits and limitations. This review aims to outline the current state-of-the-art techniques and point out their benefits and limitations.
      PubDate: 2016-04-28T15:54:02Z
      DOI: 10.12688/f1000research.8151.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding psoriasis [version 1; referees: 2

    • Abstract: T helper (Th) cells producing interleukin (IL)-17, IL-22, and tumor necrosis factor (TNF) form the key T cell population driving psoriasis pathogenesis. They orchestrate the inflammation in the skin that results in the proliferation of keratinocytes and endothelial cells. Besides Th17 cells, other immune cells that are capable of producing IL-17-associated cytokines participate in psoriatic inflammation. Recent advances in psoriasis research improved our understanding of the cellular and molecular players that are involved in Th17 pathology and inflammatory pathways in the skin. The inflammation-driving actions of TNF in psoriasis are already well known and antibodies against TNF are successful in the treatment of Th17-mediated psoriatic skin inflammation. A further key cytokine with potent IL-17-/IL-22-promoting properties is IL-23. Therapeutics directly neutralizing IL-23 or IL-17 itself are now extending the therapeutic spectrum of antipsoriatic agents and further developments are on the way. The enormous progress in psoriasis research allows us to control this Th17-mediated inflammatory skin disease in many patients.
      PubDate: 2016-04-28T09:50:36Z
      DOI: 10.12688/f1000research.7927.1
      Issue No: Vol. 5 (2016)
  • Recent advances in the management of Hodgkin lymphoma [version 1;
           referees: 3 approved]

    • Authors: Jose C. Villasboas, Stephen M. Ansell
      Abstract: Hodgkin lymphoma (HL) is a rare cancer of the immune system that typically affects lymph nodes and sometimes other organs. Although the majority of patients can be potentially cured with the use of multi-agent chemotherapy and radiotherapy, a proportion of them will relapse or develop resistant disease for which treatment options are limited. In recent years, new agents have been developed and tested in HL with encouraging results. Two classes of drugs stand out as highly active in advanced HL based on recent study results: antibody-drug conjugates and programmed death 1 inhibitors. Clinical trials in HL with these agents have been completed in the past several years and the results have recently become available. In this review, we discuss the recent advances in the management of HL with a focus on strategies to decrease toxicity and a review of the two drug classes that have the potential to change the landscape of treatment of this disease.
      PubDate: 2016-04-27T14:54:01Z
      DOI: 10.12688/f1000research.8301.1
      Issue No: Vol. 5 (2016)
  • Regulation of Microtubule Dynamics in Axon Regeneration: Insights from C.
           elegans [version 1; referees: 3 approved]

    • Authors: Ngang Heok Tang, Andrew D. Chisholm
      Abstract: The capacity of an axon to regenerate is regulated by its external environment and by cell-intrinsic factors. Studies in a variety of organisms suggest that alterations in axonal microtubule (MT) dynamics have potent effects on axon regeneration. We review recent findings on the regulation of MT dynamics during axon regeneration, focusing on the nematode Caenorhabditis elegans. In C. elegans the dual leucine zipper kinase (DLK) promotes axon regeneration, whereas the exchange factor for Arf6 (EFA-6) inhibits axon regeneration. Both DLK and EFA-6 respond to injury and control axon regeneration in part via MT dynamics. How the DLK and EFA-6 pathways are related is a topic of active investigation, as is the mechanism by which EFA-6 responds to axonal injury. We evaluate potential candidates, such as the MT affinity-regulating kinase PAR-1/MARK, in regulation of EFA-6 and axonal MT dynamics in regeneration.
      PubDate: 2016-04-27T11:19:34Z
      DOI: 10.12688/f1000research.8197.1
      Issue No: Vol. 5 (2016)
  • Is there still a role for thyroid scintigraphy in the workup of a thyroid
           nodule in the era of fine needle aspiration cytology and molecular
           testing' [version 1; referees: 3 approved]

    • Authors: Rodrigo Moreno-Reyes, Aglaia Kyrilli, Maria Lytrivi, Carole Bourmorck, Rayan Chami, Bernard Corvilain
      Abstract: Thyroid scintigraphy is now rarely used in the work-up of a thyroid nodule except in the presence of a low TSH value. Therefore, autonomously functioning thyroid nodules (AFTNs) with a normal TSH value are diagnosed only in the rare medical centers that continue to use thyroid scan systematically in the presence of a thyroid nodule. In this review, we discuss the prevalence of AFTN with a normal TSH level and the possible consequences of performing fine needle aspiration cytology (FNAC) in an undiagnosed AFTN. We also discuss the risk of malignant AFTN which may be higher than previously stated.
      PubDate: 2016-04-27T10:05:07Z
      DOI: 10.12688/f1000research.7880.1
      Issue No: Vol. 5 (2016)
  • Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma
           severity [version 1; referees: 2 approved]

    • Authors: Yalong Dang, Pritha Roy, Igor I. Bussel, Ralitsa T. Loewen, Hardik Parikh, Nils A. Loewen
      Abstract: Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities.
      PubDate: 2016-04-27T09:15:06Z
      DOI: 10.12688/f1000research.8448.1
      Issue No: Vol. 5 (2016)
  • Use of cidofovir in pediatric patients with adenovirus infection [version
           1; referees: 2 approved]

    • Authors: Lakshmi Ganapathi, Alana Arnold, Sarah Jones, Al Patterson, Dionne Graham, Marvin Harper, Ofer Levy
      Abstract: Background: Adenoviruses contribute to morbidity and mortality among immunocompromised pediatric patients including stem cell and solid organ transplant recipients. Cidofovir (CDV), an antiviral compound approved by the FDA in 1996, is used for treatment of adenoviral (ADV) infections in immunocompromised patients despite concern of potential nephrotoxicity.   Methods: We conducted a retrospective 5-year review at Boston Children’s Hospital of 16 patients (mean age = 6.5 years) receiving 19 courses of CDV. During therapy all pertinent data elements were reviewed to characterize potential response to therapy and incidence of renal dysfunction.   Results: Of the 19 CDV courses prescribed, 16 courses (84%) were in patients who had a positive blood ADV Polymerase chain reaction (PCR) alone or in combination with positive ADV PCR/ Direct Immunofluorescence Assay (DFA) at another site. Respiratory symptoms with or without pneumonia were the most common presentation (10/19, 53%). In the majority of blood positive courses (10/16, 63%), viral clearance was also accompanied by clinical response. This was not the case in four courses where patients expired despite viral clearance, including one in which death was directly attributable to adenovirus. There was reversible renal dysfunction observed during the use of CDV. Conclusions:  CDV appeared safe and reasonably tolerated for treatment of ADV in this pediatric population and was associated with viral response and clinical improvement in the majority of patients but reversible renal dysfunction was a side effect. Further studies of the efficacy of CDV for immunocompromised children with ADV infection are warranted.
      PubDate: 2016-04-26T15:53:07Z
      DOI: 10.12688/f1000research.8374.1
      Issue No: Vol. 5 (2016)
  • The myofibroblast in wound healing and fibrosis: answered and unanswered
           questions [version 1; referees: 2 approved]

    • Authors: Marie-Luce Bochaton-Piallat, Giulio Gabbiani, Boris Hinz
      Abstract: The discovery of the myofibroblast has allowed definition of the cell responsible for wound contraction and for the development of fibrotic changes. This review summarizes the main features of the myofibroblast and the mechanisms of myofibroblast generation. Myofibroblasts originate from a variety of cells according to the organ and the type of lesion. The mechanisms of myofibroblast contraction, which appear clearly different to those of smooth muscle cell contraction, are described. Finally, we summarize the possible strategies in order to reduce myofibroblast activities and thus influence several pathologies, such as hypertrophic scars and organ fibrosis.
      PubDate: 2016-04-26T11:30:36Z
      DOI: 10.12688/f1000research.8190.1
      Issue No: Vol. 5 (2016)
  • Extracorporeal membrane oxygenation 2016: an update [version 1; referees:
           3 approved]

    • Authors: Warwick Butt, Graeme MacLaren
      Abstract: The use of extracorporeal membrane oxygenation (ECMO) is an important issue for intensivists, critical care nurses, surgeons, cardiologists, and many others. There has been a continued increase in the number of centres performing ECMO. This review examines novel applications and recent trends in the use of ECMO over the last 2 years. These include ECMO to facilitate the safe use of other treatments, changing the timing of initiation, newer equipment and better biocompatibility, and the ability of ECMO programs to essentially choose which cluster of potential complications they are prepared to accept. ECMO continues to evolve, diversify in its applications, and improve in safety.
      PubDate: 2016-04-26T10:09:09Z
      DOI: 10.12688/f1000research.8320.1
      Issue No: Vol. 5 (2016)
  • The dynamics of spatio-temporal Rho GTPase signaling: formation of
           signaling patterns [version 1; referees: 2 approved]

    • Authors: Rafael Dominik Fritz, Olivier Pertz
      Abstract: Rho GTPases are crucial signaling molecules that regulate a plethora of biological functions. Traditional biochemical, cell biological, and genetic approaches have founded the basis of Rho GTPase biology. The development of biosensors then allowed measuring Rho GTPase activity with unprecedented spatio-temporal resolution. This revealed that Rho GTPase activity fluctuates on time and length scales of tens of seconds and micrometers, respectively. In this review, we describe Rho GTPase activity patterns observed in different cell systems. We then discuss the growing body of evidence that upstream regulators such as guanine nucleotide exchange factors and GTPase-activating proteins shape these patterns by precisely controlling the spatio-temporal flux of Rho GTPase activity. Finally, we comment on additional mechanisms that might feed into the regulation of these signaling patterns and on novel technologies required to dissect this spatio-temporal complexity.
      PubDate: 2016-04-26T10:07:46Z
      DOI: 10.12688/f1000research.7370.1
      Issue No: Vol. 5 (2016)
  • Recent advances in understanding Kaposi’s sarcoma-associated
           herpesvirus [version 1; referees: 2 approved]

    • Authors: Nathan J. Dissinger, Blossom Damania
      Abstract: Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic human herpesvirus. KSHV is associated with three cancers in the human population: KS, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KS is the leading cause of cancer in HIV-infected individuals. In this review, we discuss the most recent discoveries behind the mechanisms of KSHV latency maintenance and lytic replication. We also review current therapies for KSHV-associated cancers.
      PubDate: 2016-04-25T14:08:59Z
      DOI: 10.12688/f1000research.7612.1
      Issue No: Vol. 5 (2016)
  • Early detection of lung cancer [version 1; referees: 3 approved]

    • Authors: David E. Midthun
      Abstract: Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer.
      PubDate: 2016-04-25T14:02:31Z
      DOI: 10.12688/f1000research.7313.1
      Issue No: Vol. 5 (2016)
  • Updates in diabetic peripheral neuropathy [version 1; referees: 3

    • Authors: Kelsey Juster-Switlyk, A. Gordon Smith
      Abstract: Diabetes has become one of the largest global health-care problems of the 21st century. According to the Centers for Disease Control and Prevention, the population prevalence of diabetes in the US is approaching 10% and is increasing by 5% each year. Diabetic neuropathy is the most common complication associated with diabetes mellitus. Diabetes causes a broad spectrum of neuropathic complications, including acute and chronic forms affecting each level of the peripheral nerve, from the root to the distal axon. This review will focus on the most common form, distal symmetric diabetic polyneuropathy. There has been an evolution in our understanding of the pathophysiology and the management of diabetic polyneuropathy over the past decade. We highlight these new perspectives and provide updates from the past decade of research.
      PubDate: 2016-04-25T13:56:25Z
      DOI: 10.12688/f1000research.7898.1
      Issue No: Vol. 5 (2016)
  • A curated compendium of monocyte transcriptome datasets of relevance to
           human monocyte immunobiology research [version 2; referees: 2 approved]

    • Authors: Darawan Rinchai, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Damien Chaussabel
      Abstract: Systems-scale profiling approaches have become widely used in translational research settings. The resulting accumulation of large-scale datasets in public repositories represents a critical opportunity to promote insight and foster knowledge discovery. However, resources that can serve as an interface between biomedical researchers and such vast and heterogeneous dataset collections are needed in order to fulfill this potential. Recently, we have developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB). This tool can be used to overlay deep molecular phenotyping data with rich contextual information about analytes, samples and studies along with ancillary clinical or immunological profiling data. In this note, we describe a curated compendium of 93 public datasets generated in the context of human monocyte immunological studies, representing a total of 4,516 transcriptome profiles. Datasets were uploaded to an instance of GXB along with study description and sample annotations. Study samples were arranged in different groups. Ranked gene lists were generated based on relevant group comparisons. This resource is publicly available online at
      PubDate: 2016-04-25T10:50:23Z
      DOI: 10.12688/f1000research.8182.2
      Issue No: Vol. 5 (2016)
  • Uptake of dietary milk miRNAs by adult humans: a validation study [version
           1; referees: 2 approved]

    • Authors: Amanda Auerbach, Gopi Vyas, Anne Li, Marc Halushka, Kenneth Witwer
      Abstract: Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs). In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq) data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans.
      PubDate: 2016-04-22T08:53:14Z
      DOI: 10.12688/f1000research.8548.1
      Issue No: Vol. 5 (2016)
  • Effect of LXR/RXR agonism on brain and CSF Aβ40 levels in rats
           [version 2; referees: 1 approved, 2 approved with reservations]

    • Authors: Songli Wang, Paul Wen, Stephen Wood
      Abstract: Alzheimer's disease (AD) is characterized pathologically by the presence of amyloid plaques and neurofibrillary tangles. The amyloid hypothesis contends that the abnormal accumulation of Aβ, the principal component of amyloid plaques, plays an essential role in initiating the disease. Impaired clearance of soluble Aβ from the brain, a process facilitated by apolipoprotein E (APOE), is believed to be a contributing factor in plaque formation. APOE expression is transcriptionally regulated through the action of a family of nuclear receptors including the peroxisome proliferator-activated receptor gamma and liver X receptors (LXRs) in coordination with retinoid X receptors (RXRs). It has been previously reported that various agonists of this receptor family can influence brain Aβ levels in rodents. In this study we investigated the effects of LXR/RXR agonism on brain and cerebrospinal fluid (CSF) levels of Aβ40 in naïve rats. Treatment of rats for 3 days or 7 days with the LXR agonist, T0901317 or the RXR agonist, bexarotene did not result in significant changes in brain or CSF Aβ40 levels.
      PubDate: 2016-04-19T15:58:01Z
      DOI: 10.12688/f1000research.7868.2
      Issue No: Vol. 5 (2016)
  • Provisional Tic Disorder: What to tell parents when their child first
           starts ticcing [version 1; referees: 2 approved]

    • Authors: Kevin J Black, Elizabeth Rose Black, Deanna J. Greene, Bradley L. Schlaggar
      Abstract: The child with recent onset of tics is a common patient in a pediatrics or child neurology practice. If the child’s first tic was less than a year in the past, the diagnosis is usually Provisional Tic Disorder (PTD). Published reviews by experts reveal substantial consensus on prognosis in this situation: the tics will almost always disappear in a few months, having remained mild while they lasted. Surprisingly, however, the sparse existing data may not support these opinions. PTD may have just as much importance for science as for clinical care. It provides an opportunity to prospectively observe the spontaneous remission of tics. Such prospective studies may aid identification of genes or biomarkers specifically associated with remission rather than onset of tics. A better understanding of tic remission may also suggest novel treatment strategies for Tourette syndrome, or may lead to secondary prevention of tic disorders. This review summarizes the limited existing data on the epidemiology, phenomenology, and outcome of PTD, highlights areas in which prospective study is sorely needed, and proposes that tic disorders may completely remit much less often than is generally believed.
      PubDate: 2016-04-18T14:08:32Z
      DOI: 10.12688/f1000research.8428.1
      Issue No: Vol. 5 (2016)
  • Flagellar membrane fusion and protein exchange in trypanosomes; a new form
           of cell-cell communication' [version 1; referees: 2 approved]

    • Authors: Simon Imhof, Cristina Fragoso, Andrew Hemphill, Conrad von Schubert, Dong Li, Wesley Legant, Eric Betzig, Isabel Roditi
      Abstract: Diverse structures facilitate direct exchange of proteins between cells, including plasmadesmata in plants and tunnelling nanotubes in bacteria and higher eukaryotes.  Here we describe a new mechanism of protein transfer, flagellar membrane fusion, in the unicellular parasite Trypanosoma brucei. When fluorescently tagged trypanosomes were co-cultured, a small proportion of double-positive cells were observed. The formation of double-positive cells was dependent on the presence of extracellular calcium and was enhanced by placing cells in medium supplemented with fresh bovine serum. Time-lapse microscopy revealed that double-positive cells arose by bidirectional protein exchange in the absence of nuclear transfer.  Furthermore, super-resolution microscopy showed that this process occurred in ≤1 minute, the limit of temporal resolution in these experiments. Both cytoplasmic and membrane proteins could be transferred provided they gained access to the flagellum. Intriguingly, a component of the RNAi machinery (Argonaute) was able to move between cells, raising the possibility that small interfering RNAs are transported as cargo. Transmission electron microscopy showed that shared flagella contained two axonemes and two paraflagellar rods bounded by a single membrane. In some cases flagellar fusion was partial and interactions between cells were transient. In other cases fusion occurred along the entire length of the flagellum, was stable for several hours and might be irreversible. Fusion did not appear to be deleterious for cell function: paired cells were motile and could give rise to progeny while fused. The motile flagella of unicellular organisms are related to the sensory cilia of higher eukaryotes, raising the possibility that protein transfer between cells via cilia or flagella occurs more widely in nature.
      PubDate: 2016-04-14T11:18:00Z
      DOI: 10.12688/f1000research.8249.1
      Issue No: Vol. 5 (2016)
  • MetaNetVar: Pipeline for applying network analysis tools for genomic
           variants analysis [version 1; referees: 2 approved]

    • Authors: Eric Moyer, Megan Hagenauer, Matthew Lesko, Felix Francis, Oscar Rodriguez, Vijayaraj Nagarajan, Vojtech Huser, Ben Busby
      Abstract: Network analysis can make variant analysis better. There are existing tools like HotNet2 and dmGWAS that can provide various analytical methods. We developed a prototype of a pipeline called MetaNetVar that allows execution of multiple tools. The code is published at A working prototype is published as an Amazon Machine Image - ami-4510312f .
      PubDate: 2016-04-13T14:17:34Z
      DOI: 10.12688/f1000research.8288.1
      Issue No: Vol. 5 (2016)
  • Case Report: Multifocal biphasic squamoid alveolar renal cell carcinoma
           [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: Jose Ignacio Lopez
      Abstract: A multifocal biphasic squamoid alveolar renal cell carcinoma in a 68-year-old man is reported. Four different peripheral tumor nodules were identified on gross examination. A fifth central tumor corresponded to a conventional clear cell renal cell carcinoma. Biphasic squamoid alveolar renal cell carcinoma is a rare tumor that has been very recently characterized as a distinct histotype within the spectrum of papillary renal cell carcinoma. Immunostaining with cyclin D1 seems to be specific of this tumor subtype. This is the first reported case with multifocal presentation.
      PubDate: 2016-04-08T14:29:35Z
      DOI: 10.12688/f1000research.8451.1
      Issue No: Vol. 5 (2016)
  • Possible repurposing of seasonal influenza vaccine for prevention of Zika
           virus infection [version 2; referees: 2 approved]

    • Authors: Veljko Veljkovic, Slobodan Paessler
      Abstract: The in silico analysis shows that the envelope glycoproteins E of Zika viruses (ZIKV) isolated in Asia, Africa and South and Central America encode highly conserved information determining their interacting profile and immunological properties. Previously it was shown that the same information is encoded in the primary structure of the hemagglutinin subunit 1 (HA1) from pdmH1N1 influenza A virus.  This similarity suggests possible repurposing of the seasonal influenza vaccine containing pdmH1N1 component for prevention of the ZIKV infection.
      PubDate: 2016-03-23T16:41:36Z
      DOI: 10.12688/f1000research.8102.2
      Issue No: Vol. 5 (2016)
  • The ICR142 NGS validation series: a resource for orthogonal assessment of
           NGS analysis [version 1; referees: 2 approved]

    • Authors: Elise Ruark, Anthony Renwick, Matthew Clarke, Katie Snape, Emma Ramsay, Anna Elliott, Sandra Hanks, Ann Strydom, Sheila Seal, Nazneen Rahman
      Abstract: To provide a useful community resource for orthogonal assessment of NGS analysis software, we present the ICR142 NGS validation series. The dataset includes high-quality exome sequence data from 142 samples together with Sanger sequence data at 730 sites; 409 sites with variants and 321 sites at which variants were called by an NGS analysis tool, but no variant is present in the corresponding Sanger sequence. The dataset includes 286 indel variants and 275 negative indel sites, and thus the ICR142 validation dataset is of particular utility in evaluating indel calling performance. The FASTQ files and Sanger sequence results can be accessed in the European Genome-phenome Archive under the accession number EGAS00001001332.
      PubDate: 2016-03-22T16:24:37Z
      DOI: 10.12688/f1000research.8219.1
      Issue No: Vol. 5 (2016)
  • Promoting development and uptake of health innovations: The Nose to Tail
           Tool [version 1; referees: 2 approved]

    • Authors: Archna Gupta, Cathy Thorpe, Onil Bhattacharyya, Merrick Zwarenstein
      Abstract: Introduction Health sector management is increasingly complex as new health technologies, treatments, and innovative service delivery strategies are developed. Many of these innovations are implemented prematurely, or fail to be implemented at scale, resulting in substantial wasted resources.   Methods A scoping review was conducted to identify articles that described the scale up process conceptually or that described an instance in which a healthcare innovation was scaled up. We define scale up as the expansion and extension of delivery or access to an innovation for all end users in a jurisdiction who will benefit from it. Results Sixty nine articles were eligible for review. Frequently described stages in the innovation process and contextual issues that influence progress through each stage were mapped. 16 stages were identified: 12 deliberation and 4 action stages. Included papers suggest that innovations progress through stages of maturity and the uptake of innovation depends on the innovation aligning with the interests of 3 critical stakeholder groups (innovators, end users and the decision makers) and is also influenced by 3 broader contexts (social and physical environment, the health system, and the regulatory, political and economic environment). The 16 stages form the rows of the Nose to Tail Tool (NTT) grid and the 6 contingency factors form columns. The resulting stage-by-issue grid consists of 72 cells, each populated with cell-specific questions, prompts and considerations from the reviewed literature. Conclusion We offer a tool that helps stakeholders identify the stage of maturity of their innovation, helps facilitate deliberative discussions on the key considerations for each major stakeholder group and the major contextual barriers that the innovation faces. We believe the NTT will help to identify potential problems that the innovation will face and facilitates early modification, before large investments are made in a potentially flawed solution.
      PubDate: 2016-03-16T11:54:08Z
      DOI: 10.12688/f1000research.8145.1
      Issue No: Vol. 5 (2016)
  • Surveillance, insecticide resistance and control of an invasive Aedes
           aegypti (Diptera: Culicidae) population in California [version 2;
           referees: 2 approved]

    • Authors: Anthony J. Cornel, Jodi Holeman, Catelyn C. Nieman, Yoosook Lee, Charles Smith, Mark Amorino, Katherine K. Brisco, Roberto Barrera, Gregory C. Lanzaro, F. Stephen Mulligan III
      Abstract: The invasion and subsequent establishment in California of Aedes aegypti in 2013 has created new challenges for local mosquito abatement and vector control districts. Studies were undertaken to identify effective and economical strategies to monitor the abundance and spread of this mosquito species as well as for its control. Overall, BG Sentinel (BGS) traps were found to be the most sensitive trap type to measure abundance and spread into new locations. Autocidal-Gravid-Ovitraps (AGO-B), when placed at a site for a week, performed equally to BGS in detecting the presence of female Ae. aegypti. Considering operational cost and our findings, we recommend use of BGS traps for surveillance in response to service requests especially in locations outside the known infestation area. We recommend AGO-Bs be placed at fixed sites, cleared and processed once a week to monitor mosquito abundance within a known infestation area. Long-term high density placements of AGO-Bs were found to show promise as an environmentally friendly trap-kill control strategy. California Ae. aegypti were found to be homozygous for the V1016I mutation in the voltage gated sodium channel gene, which is implicated to be involved in insecticide resistance. This strain originating from Clovis, California was resistant to some pyrethroids but not to deltamethrin in bottle bio-assays. Sentinel cage ultra-low-volume (ULV) trials using a new formulation of deltamethrin (DeltaGard®) demonstrated that it provided some control (average of 56% death in sentinel cages in a 91.4 m spray swath) after a single truck mounted aerial ULV application in residential areas.
      PubDate: 2016-03-07T14:00:41Z
      DOI: 10.12688/f1000research.8107.2
      Issue No: Vol. 5 (2016)
  • Acceptance of animal research in our science community [version 1;
           referees: 2 approved]

    • Authors: Konstantin Bergmeister, Bruno Podesser
      Abstract: Animal research is debated highly controversial, as evident by the “Stop Vivi-section” initiative in 2015. Despite widespread protest to the initiative by researchers, no data is available on the European medical research community’s opinion towards animal research. In this single-center study, we investigated this question in a survey of students and staff members at the Medical University of Vienna. A total of 906 participants responded to the survey, of which 82.8% rated the relevance of animal research high and 62% would not accept a treatment without prior animals testing. Overall, animal research was considered important, but its communication to the public considered requiring improvement.
      PubDate: 2016-03-04T15:43:11Z
      DOI: 10.12688/f1000research.8169.1
      Issue No: Vol. 5 (2016)
  • How blockchain-timestamped protocols could improve the trustworthiness of
           medical science [version 1; referees: 2 approved]

    • Authors: Greg Irving, John Holden
      Abstract: Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Here we report a proof-of-concept study  using a ‘blockchain’ as a low cost, independently verifiable method that could be widely and readily used to audit and confirm the reliability of scientific studies.
      PubDate: 2016-02-26T11:26:16Z
      DOI: 10.12688/f1000research.8114.1
      Issue No: Vol. 5 (2016)
  • Enteropathogenic E. coli: breaking the intestinal tight junction barrier
           [version 2; referees: 2 approved]

    • Authors: Anand Prakash Singh, Saima Aijaz
      Abstract: Enteropathogenic E. coli (EPEC) causes acute intestinal infections in infants in the developing world. Infection typically spreads through contaminated food and water and leads to severe, watery diarrhea. EPEC attaches to the intestinal epithelial cells and directly injects virulence factors which modulate multiple signaling pathways leading to host cell dysfunction. However, the molecular mechanisms that regulate the onset of diarrhea are poorly defined. A major target of EPEC is the host cell tight junction complex which acts as a barrier and regulates the passage of water and solutes through the paracellular space. In this review, we focus on the EPEC effectors that target the epithelial barrier, alter its functions and contribute to leakage through the tight junctions.
      PubDate: 2016-05-04T11:48:05Z
      DOI: 10.12688/f1000research.6778.2
      Issue No: Vol. 4 (2016)
  • Semi-automated Modular Program Constructor for physiological modeling:
           Building cell and organ models [version 2; referees: 2 approved]

    • Authors: Bartholomew Jardine, Gary M. Raymond, James B. Bassingthwaighte
      Abstract: The Modular Program Constructor (MPC) is an open-source Java based modeling utility, built upon JSim's Mathematical Modeling Language (MML) ( that uses directives embedded in model code to construct larger, more complicated models quickly and with less error than manually combining models. A major obstacle in writing complex models for physiological processes is the large amount of time it takes to model the myriad processes taking place simultaneously in cells, tissues, and organs. MPC replaces this task with code-generating algorithms that take model code from several different existing models and produce model code for a new JSim model. This is particularly useful during multi-scale model development where many variants are to be configured and tested against data. MPC encodes and preserves information about how a model is built from its simpler model modules, allowing the researcher to quickly substitute or update modules for hypothesis testing. MPC is implemented in Java and requires JSim to use its output. MPC source code and documentation are available at
      PubDate: 2016-04-06T10:12:09Z
      DOI: 10.12688/f1000research.7476.2
      Issue No: Vol. 4 (2016)
  • Adrenocorticotropic hormone gel in the treatment of systemic lupus
           erythematosus: A retrospective study of patients. [version 2; referees: 2

    • Authors: Xiao Li, Josh Golubovsky, Joyce Hui-Yuen, Ummara Shah, Ewa Olech, Rosalia Lomeo, Vijay Singh, Howard Busch, Mary Jane Strandberg, Kayla Strandberg, Leslie Horowitz, Anca Askanase
      Abstract: Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity.
      PubDate: 2016-02-24T15:57:51Z
      DOI: 10.12688/f1000research.7192.2
      Issue No: Vol. 4 (2016)
  • Case Report: A case report of dry tap during ventriculostomy [version 2;
           referees: 2 approved, 1 approved with reservations]

    • Authors: Sunil Munakomi, Binod Bhattarai
      Abstract: Pneumocephalus following ventriculoperitoneal (VP) shunt insertion is an exceptionally rare occurrence. We report such an event after attempting ventricular puncture (ventriculostomy) for VP shunt insertion and then discuss the management of the same. Dry tap can lead to multiple attempts for ventriculostomy with the associated added risks of complications, as well as complicating the subsequent management. In addition, there is an increased risk of tension pneumocephalus, seizure and shunt failure due to a blockage by air bubbles. Our patient presented with features of raised intracranial pressure two months following craniotomy and evacuation of traumatic subdural hematoma. External ventricular puncture revealed egress of CSF under pressure. Upon attempting VP shunting for post-traumatic hydrocephalus, we experienced dry tap during ventricular puncture that complicated further management. We placed the proximal shunt in the presumed location of the foramen of Monro of ipsilateral frontal horn of lateral ventricle and did not remove the external ventricular drain. Post-operative CT scan revealed pneumoventriculi as the cause for the dry tap during ventricular puncture. Patient was managed with 100% oxygen. He showed gradual improvement and was later discharged. This case shows that variations in the procedure, including head down positioning, adequate cruciate dural incision prior to cortex puncture, and avoiding excessive egress of CSF can help to prevent such complications.
      PubDate: 2015-10-02T14:48:04Z
      DOI: 10.12688/f1000research.6750.2
      Issue No: Vol. 4 (2015)
  • Macrophage migration inhibitory factor and placental malaria infection in
           an area characterized by unstable malaria transmission in central Sudan
           [version 1; referees: 2 approved]

    • Authors: Reem Eltayeb, Naser Bilal, Awad-Elkareem Abass, Elhassan M. Elhassan, Ahmed Mohammed, Ishag Adam
      Abstract: Background: The pathogenesis of malaria during pregnancy is not fully understood. A proinflammatory cytokine, macrophage migration inhibitory factor (MIF) is suggested as a factor involved in the pathogenesis of malaria during pregnancy. Methods: A cross-sectional study was conducted in Medani Hospital, Sudan to investigate MIF levels in placental malaria. Obstetrical and medical characteristics were gathered from each parturient woman using questionnaires. All women (151) were investigated for malaria using blood film and placental histology. MIF levels were measured using ELISA in paired maternal and cord blood samples. Results: There were no P. falciparum-positive blood films obtained from maternal peripheral blood, placenta or cord samples. Out of 151 placentae, four (2.6%), one (0.7%), 32 (21.2%) showed acute, chronic and past infection on histopathology examinations respectively, while the rest (114; 75.5%) of them showed no signs of infection.There was no significant difference in the median (interquartile) of maternal [5.0 (3.7─8.8) vs 6.2(3.5─12.0) ng/ml, P=0.643] and cord [8.1(3.3─16.9) vs 8.3(4.2─16.9), ng/ml, P= 0.601] MIF levels between women with a positive result for placental malaria infection (n=37) and women with a negative result for placental malaria infection (n=114). In regression models placental malaria was not associated with maternal MIF, hemoglobin or birth weight. MIF was not associated with hemoglobin or birth weight. Conclusion: There was no association between maternal and cord MIF levels, placental malaria, maternal hemoglobin and birth weight.
      PubDate: 2015-09-16T13:47:58Z
      DOI: 10.12688/f1000research.7061.1
      Issue No: Vol. 4 (2015)
  • Double blinding requirement for validity claims in cognitive-behavioral
           therapy intervention trials for major depressive disorder. Analysis
           of Hollon S, et al., Effect of cognitive therapy with antidepressant
           medications vs antidepressants alone on the rate of recovery in major
           depressive disorder: a randomized clinical trial [version 1; referees: 2

    • Authors: Douglas Berger
      Abstract: This paper will focus on problems in the inability to double-blind cognitive-behavioral therapy (CBT) studies for major depressive disorder (MDD), and provides an analysis of a recently published study to show how this problem can lead to faulty conclusions. A study by Hollon et al. published in JAMA Psychiatry that compared an antidepressant medication-only arm with a combined CBT/antidepressant arm concluded that the cognitive therapy/antidepressant combination enhanced the recovery rates compared with antidepressant alone, and that the magnitude of this increment nearly doubled for patients with more severe depression. We propose that for subjects with greater severity, there could have been both antidepressant efficacy as well as more hope and expectation in the group who knew they had received combined cognitive therapy/medication, leading to an erroneous conclusion of greater efficacy for the combined group. The large subject number in this study could easily lead to an erroneous finding on statistical testing as a small amount of bias in the subjects adds-up. We opine that the conclusions of unblind CBT outcome research in conditions with subjective endpoints such as MDD need to be given with great caution. The validity of CBT (and its derivatives such as dialectical behavioral therapy) for indications other than MDD is also part of a larger problem in  the inability to blind outcome studies for these interventions.
      PubDate: 2015-08-27T15:17:49Z
      DOI: 10.12688/f1000research.6954.1
      Issue No: Vol. 4 (2015)
  • Rapid assessment of iron in blood plasma and serum by spectrophotometry
           with cloud-point extraction [version 1; referees: 2 approved]

    • Authors: Tatyana Samarina, Mikhail Proskurnin
      Abstract: Rapid photometric assessment of iron in blood plasma and serum by a simple procedure after the extraction of iron(II) complex with 1-nitroso-2-naphthol in the micellar phase of a nonionic surfactant at the cloud point upon heating (pH range is 4.5–6.3) is proposed. The procedure trueness was verified using a standard reference protocol using bathophenanthroline. The advantages of the procedure are higher sensitivity than the reference protocol: the limit of detection is 0.03 μg/mL, the limit of quantitation is 0.1 μg/mL, the determination range is 0.1 – 2.8 μg/mL (RSD 0.02–0.10). Copper does not interfere with the iron assessment.
      PubDate: 2015-08-25T13:17:51Z
      DOI: 10.12688/f1000research.6716.1
      Issue No: Vol. 4 (2015)
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