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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]
  • Does the human immune system ever really become “senescent”'
           [version 1; referees: 5 approved]

    • Authors: Graham Pawelec
      Abstract: Like all somatic tissues, the human immune system changes with age. This is believed to result in an increased frequency of, and susceptibility to, infectious disease and to contribute to a wide range of non-communicable age-associated diseases in later life, especially cancer, cardiovascular disease, and autoimmunity. The majority of studies addressing immune ageing has been cross-sectional, but limited longitudinal studies are contributing to a better understanding of age-associated changes, as opposed to differences, and their clinical relevance. However, intriguing differences are emerging that implicate highly context-dependent immune ageing processes, mitigating against current generalisations concerning human immunosenescence and indicating the necessity for detailed comparisons of different populations, even those that would appear quite similar at first glance.
      PubDate: 2017-08-04T10:00:20Z
      DOI: 10.12688/f1000research.11297.1
      Issue No: Vol. 6 (2017)
       
  • ChemMaps: Towards an approach for visualizing the chemical space based on
           adaptive satellite compounds [version 2; referees: 1 approved, 2 approved
           with reservations]

    • Authors: J. Jesús Naveja, José L. Medina-Franco
      Abstract: We present a novel approach called ChemMaps for visualizing chemical space based on the similarity matrix of compound datasets generated with molecular fingerprints’ similarity. The method uses a ‘satellites’ approach, where satellites are, in principle, molecules whose similarity to the rest of the molecules in the database provides sufficient information for generating a visualization of the chemical space. Such an approach could help make chemical space visualizations more efficient. We hereby describe a proof-of-principle application of the method to various databases that have different diversity measures. Unsurprisingly, we found the method works better with databases that have low 2D diversity. 3D diversity played a secondary role, although it seems to be more relevant as 2D diversity increases. For less diverse datasets, taking as few as 25% satellites seems to be sufficient for a fair depiction of the chemical space. We propose to iteratively increase the satellites number by a factor of 5% relative to the whole database, and stop when the new and the prior chemical space correlate highly. This Research Note represents a first exploratory step, prior to the full application of this method for several datasets.
      PubDate: 2017-08-04T08:46:09Z
      DOI: 10.12688/f1000research.12095.2
      Issue No: Vol. 6 (2017)
       
  • Toward an understanding of the Cdc48/p97 ATPase [version 1; referees: 4
           approved]

    • Authors: Nicholas Bodnar, Tom Rapoport
      Abstract: A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore. Cdc48/p97 cooperates with a number of different cofactors, which bind either to the N-terminal domain or to the C-terminal tail. The mechanism of Cdc48/p97 action is poorly understood, despite its critical role in many cellular systems. Recent in vitro experiments using yeast Cdc48 and its heterodimeric cofactor Ufd1/Npl4 (UN) have resulted in novel mechanistic insight. After interaction of the substrate-attached polyubiquitin chain with UN, Cdc48 uses ATP hydrolysis in the D2 domain to move the polypeptide through its central pore, thereby unfolding the substrate. ATP hydrolysis in the D1 domain is involved in substrate release from the Cdc48 complex, which requires the cooperation of the ATPase with a deubiquitinase (DUB). Surprisingly, the DUB does not completely remove all ubiquitin molecules; the remaining oligoubiquitin chain is also translocated through the pore. Cdc48 action bears similarities to the translocation mechanisms employed by bacterial AAA ATPases and the eukaryotic 19S subunit of the proteasome, but differs significantly from that of a related type II ATPase, the NEM-sensitive fusion protein (NSF). Many questions about Cdc48/p97 remain unanswered, including how it handles well-folded substrate proteins, how it passes substrates to the proteasome, and how various cofactors modify substrates and regulate its function.
      PubDate: 2017-08-03T14:35:04Z
      DOI: 10.12688/f1000research.11683.1
      Issue No: Vol. 6 (2017)
       
  • Advances on minimally invasive approach for benign total hysterectomy: a
           systematic review [version 1; referees: 2 approved]

    • Authors: Marina de Paula Andres, Giuliano Moysés Borrelli, Mauricio Simões Abrão
      Abstract: Hysterectomy is one of the most commonly performed gynecologic surgeries, mainly for uterine myomas, abnormal uterine bleeding, and prolapses. It can be performed through several routes, each of which has its advantages and disadvantages. We conducted this systematic review to evaluate recent advances in surgical outcomes of benign total hysterectomies by any route: vaginal (VH), laparoscopic (LH), laparoscopically assisted vaginal (LAVH), single-port (SP), and robotic-assisted laparoscopy (RH). The search was applied to the PubMed electronic database by using keywords “hysterectomy” and “uterine benign disease”, “adenomyosis”, and “myoma”. Prospective and randomized trials of the last 3 years were included. Nine studies were selected and showed that VH was superior to LH, LAVH, and RH in terms of hospital stay and operation time and had the same complication rate and lower costs. SP hysterectomy had no clear advantages over VH or conventional LH.
      PubDate: 2017-08-01T15:36:56Z
      DOI: 10.12688/f1000research.11523.1
      Issue No: Vol. 6 (2017)
       
  • Therapeutic potential of systemic brain rejuvenation strategies for
           neurodegenerative disease [version 1; referees: 3 approved]

    • Authors: Alana M. Horowitz, Saul A. Villeda
      Abstract: Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.
      PubDate: 2017-08-01T13:14:47Z
      DOI: 10.12688/f1000research.11437.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in acute promyelocytic leukaemia [version 1; referees: 3
           approved]

    • Authors: Chin-Hin Ng, Wee-Joo Chng
      Abstract: Acute promyelocytic leukaemia (APML) is a subtype of leukaemia arising from a distinct reciprocal translocation involving chromosomes 15 and 17, which results in the PML-RARA fusion gene. Over the past three decades, APML has been transformed from a highly fatal disease to a highly curable one. This drastic improvement is because of the introduction of a new treatment strategy with all-trans retinoic acid and, more recently, arsenic trioxide. The revolutionary treatment of APML has also paved the way for a new cancer treatment, which is genetically targeted therapy. In this review, we look into this amazing journey of transformation and provide recent advances in the management of APML.
      PubDate: 2017-07-28T13:49:49Z
      DOI: 10.12688/f1000research.10736.1
      Issue No: Vol. 6 (2017)
       
  • Hidradenitis suppurativa: an update on connecting the tracts [version 1;
           referees: 3 approved]

    • Authors: Mallory K Smith, Cynthia L Nicholson, Angela Parks-Miller, Iltefat H Hamzavi
      Abstract: Hidradenitis suppurativa (HS) is a devastating disease involving abscesses, sinus tracts, and inflammation classically affecting the axilla, groin, and/or anogenital region. Although the disease pathogenesis is not fully understood, recent advances suggest that HS pathology runs much deeper than the cutaneous manifestations. It is now believed that HS is a systemic inflammatory disease that gives rise to the characteristic cutaneous manifestations. This disease is problematic for both patients and physicians to manage because of a variety of diagnostic and management difficulties. This article seeks to provide updates on the current understanding of HS to increase awareness and improve management.
      PubDate: 2017-07-28T13:48:47Z
      DOI: 10.12688/f1000research.11337.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in understanding Pseudomonas aeruginosa as a pathogen
           [version 1; referees: 3 approved]

    • Authors: Jens Klockgether, Burkhard Tümmler
      Abstract: The versatile and ubiquitous Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections in predisposed human subjects. Here we review recent progress in understanding P. aeruginosa population biology and virulence, its cyclic di-GMP-mediated switches of lifestyle, and its interaction with the mammalian host as well as the role of the type III and type VI secretion systems in P. aeruginosa infection.
      PubDate: 2017-07-28T09:09:46Z
      DOI: 10.12688/f1000research.10506.1
      Issue No: Vol. 6 (2017)
       
  • Adaptation in the visual cortex: a case for probing neuronal populations
           with natural stimuli [version 1; referees: 4 approved]

    • Authors: Michoel Snow, Ruben Coen-Cagli, Odelia Schwartz
      Abstract: The perception of, and neural responses to, sensory stimuli in the present are influenced by what has been observed in the past—a phenomenon known as adaptation. We focus on adaptation in visual cortical neurons as a paradigmatic example. We review recent work that represents two shifts in the way we study adaptation, namely (i) going beyond single neurons to study adaptation in populations of neurons and (ii) going beyond simple stimuli to study adaptation to natural stimuli. We suggest that efforts in these two directions, through a closer integration of experimental and modeling approaches, will enable a more complete understanding of cortical processing in natural environments.
      PubDate: 2017-07-27T13:16:01Z
      DOI: 10.12688/f1000research.11154.1
      Issue No: Vol. 6 (2017)
       
  • Unmet goals in the treatment of Acute Myocardial Infarction: Review
           [version 1; referees: 2 approved]

    • Authors: Alejandro Farah, Alejandro Barbagelata
      Abstract: Reperfusion therapy decreases myocardium damage during an acute coronary event and consequently mortality. However, there are unmet needs in the treatment of acute myocardial infarction, consequently mortality and heart failure continue to occur in about 10% and 20% of cases, respectively. Different strategies could improve reperfusion. These strategies, like generation of warning sign recognition and being initially assisted and transferred by an emergency service, could reduce the time to reperfusion. If the first electrocardiogram is performed en route, it can be transmitted and interpreted in a timely manner by a specialist at the receiving center, bypassing community hospitals without percutaneous coronary intervention capabilities. To administer thrombolytic therapy during transport to the catheterization laboratory could reduce time to reperfusion in cases with expected prolonged transport time to a percutaneous coronary intervention center or to a center without primary percutaneous coronary intervention capabilities with additional expected delay, known as pharmaco-invasive strategy. Myocardial reperfusion is known to produce damage and cell death, which defines the reperfusion injury. Lack of resolution of ST segment is used as a marker of reperfusion failure. In patients without ST segment resolution, mortality triples. It is important to note that, until recently, reperfusion injury and no-reflow were interpreted as a single entity and we should differentiate them as different entities; whereas no-reflow is the failure to obtain tissue flow, reperfusion injury is actually the damage produced by achieving flow. Therefore, treatment of no-reflow is obtained by tissue flow, whereas in reperfusion injury the treatment objective is protection of susceptible myocardium from reperfusion injury. Numerous trials for the treatment of reperfusion injury have been unsuccessful. Newer hypotheses such as “controlled reperfusion”, in which the interventional cardiologist assumes not only the treatment of the culprit vessel but also the way to reperfuse the myocardium at risk, could reduce reperfusion injury.
      PubDate: 2017-07-27T10:07:30Z
      DOI: 10.12688/f1000research.10553.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in cancer surgery in older patients [version 1; referees:
           2 approved]

    • Authors: Siri Rostoft, Riccardo A. Audisio
      Abstract: Age is the most important risk factor for the occurrence of cancer, and a declining mortality from heart disease and other non-cancer causes leaves an older population that is at high risk of developing cancer. Choosing the optimal treatment for older cancer patients may be a challenge. Firstly, older age and associated factors such as comorbidities, functional limitations, and cognitive impairment are risk factors for adverse effects of cancer treatment. Secondly, older patients are often excluded from clinical trials, and current clinical guidelines rarely address how to manage cancer in patients who have comorbidities or functional limitations. The importance of incorporating frailty assessment into the preoperative evaluation of older surgical patients has received increasing attention over the last 10 years. Furthermore, studies that include endpoints such as functional status, cognitive status, and quality of life beyond the standard endpoints, i.e. postoperative morbidity and mortality, are starting to emerge. This review looks at recent evidence regarding geriatric assessment and frailty in older surgical cancer patients and provides a summary of newer studies in colorectal, liver, pancreatic, and gynecological cancer and renal and central nervous system tumors.
      PubDate: 2017-07-27T09:24:00Z
      DOI: 10.12688/f1000research.10683.1
      Issue No: Vol. 6 (2017)
       
  • Marine archaea and archaeal viruses under global change [version 1;
           referees: 2 approved]

    • Authors: Roberto Danovaro, Eugenio Rastelli, Cinzia Corinaldesi, Michael Tangherlini, Antonio Dell'Anno
      Abstract: Global change is altering oceanic temperature, salinity, pH, and oxygen concentration, directly and indirectly influencing marine microbial food web structure and function. As microbes represent >90% of the ocean’s biomass and are major drivers of biogeochemical cycles, understanding their responses to such changes is fundamental for predicting the consequences of global change on ecosystem functioning. Recent findings indicate that marine archaea and archaeal viruses are active and relevant components of marine microbial assemblages, far more abundant and diverse than was previously thought. Further research is urgently needed to better understand the impacts of global change on virus–archaea dynamics and how archaea and their viruses can interactively influence the ocean’s feedbacks on global change.
      PubDate: 2017-07-27T09:22:41Z
      DOI: 10.12688/f1000research.11404.1
      Issue No: Vol. 6 (2017)
       
  • Natural killer cells in herpesvirus infections [version 1; referees: 2
           approved]

    • Authors: Christian Münz, Obinna Chijioke
      Abstract: Natural killer (NK) cells are potent innate cytotoxic lymphocytes for the destruction of infected and transformed cells. Although they were originally considered to be ready-made assassins after their hematopoietic development, it has recently become clear that their activity is regulated by mechanisms such as repertoire composition, licensing, priming, and adaptive memory-like differentiation. Some of these mechanisms are influenced by infectious disease agents, including herpesviruses. In this review, we will compare expansion, stimulation, and effector functions of NK cell populations after infections with β- and γ1-herpesviruses because, though closely related, these pathogens seem to drive completely opposite NK cell responses. The discussed findings suggest that different NK cell subsets expand and perform protective functions during infectious diseases and might be used diagnostically to predict resistance to the causative pathogens as well as treat them by adoptive transfer of the respective populations.
      PubDate: 2017-07-26T11:37:40Z
      DOI: 10.12688/f1000research.11197.1
      Issue No: Vol. 6 (2017)
       
  • Unraveling Neisseria meningitidis pathogenesis: from functional genomics
           to experimental models [version 1; referees: 2 approved]

    • Authors: Marco Soriani
      Abstract: Neisseria meningitidis is a harmless commensal bacterium finely adapted to humans. Unfortunately, under “privileged” conditions, it adopts a “devious” lifestyle leading to uncontrolled behavior characterized by the unleashing of molecular weapons causing potentially lethal disease such as sepsis and acute meningitis. Indeed, despite the lack of a classic repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology and functional genomics studies suggest that carriage and invasive strains belong to genetically distinct populations characterized by an exclusive pathogenic potential. In the last few years, “omics” technologies have helped scientists to unwrap the framework drawn by N. meningitidis during different stages of colonization and disease. However, this scenario is still incomplete and would benefit from the implementation of physiological tissue models for the reproduction of mucosal and systemic interactions in vitro. These emerging technologies supported by recent advances in the world of stem cell biology hold the promise for a further understanding of N. meningitidis pathogenesis.
      PubDate: 2017-07-26T09:00:13Z
      DOI: 10.12688/f1000research.11279.1
      Issue No: Vol. 6 (2017)
       
  • Co-evolution techniques are reshaping the way we do structural
           bioinformatics [version 1; referees: 2 approved]

    • Authors: Saulo de Oliveira, Charlotte Deane
      Abstract: Co-evolution techniques were originally conceived to assist in protein structure prediction by inferring pairs of residues that share spatial proximity. However, the functional relationships that can be extrapolated from co-evolution have also proven to be useful in a wide array of structural bioinformatics applications. These techniques are a powerful way to extract structural and functional information in a sequence-rich world.
      PubDate: 2017-07-25T14:34:47Z
      DOI: 10.12688/f1000research.11543.1
      Issue No: Vol. 6 (2017)
       
  • Senescence in the aging process [version 1; referees: 3 approved]

    • Authors: Richard GA Faragher, Anne McArdle, Alison Willows, Elizabeth L. Ostler
      Abstract: The accumulation of ‘senescent’ cells has long been proposed to act as an ageing mechanism. These cells display a radically altered transcriptome and degenerative phenotype compared with their growing counterparts. Tremendous progress has been made in recent years both in understanding the molecular mechanisms controlling entry into the senescent state and in the direct demonstration that senescent cells act as causal agents of mammalian ageing. The challenges now are to gain a better understanding of how the senescent cell phenotype varies between different individuals and tissues, discover how senescence predisposes to organismal frailty, and develop mechanisms by which the deleterious effects of senescent cells can be ameliorated.
      PubDate: 2017-07-25T10:29:38Z
      DOI: 10.12688/f1000research.10903.1
      Issue No: Vol. 6 (2017)
       
  • The potential role of microbiota for controlling the spread of
           extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in
           neonatal population [version 1; referees: 2 approved]

    • Authors: Thibaud Delerue, Loic de Pontual, Etienne Carbonnelle, Jean-Ralph Zahar
      Abstract: The spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in the hospital and also the community is worrisome. Neonates particularly are exposed to the risk of ESBL-PE acquisition and, owing to the immaturity of their immune system, to a higher secondary risk of ESBL-PE-related infection. Reducing the risk of acquisition in the hospital is usually based on a bundle of measures, including screening policies at admission, improving hand hygiene compliance, and decreasing antibiotic consumption. However, recent scientific data suggest new prevention opportunities based on microbiota modifications.
      PubDate: 2017-07-25T10:17:25Z
      DOI: 10.12688/f1000research.10713.1
      Issue No: Vol. 6 (2017)
       
  • Up-and-down immunity of pregnancy in humans [version 1; referees: 2
           approved]

    • Authors: Philippe Le Bouteiller, Armand Bensussan
      Abstract: One part of the human placenta in early pregnancy is particularly important for local immunity: the decidua basalis, which is transformed endometrium located at the site of embryo implantation. This placental bed tissue contains both maternal uterine immune cells, including decidual natural killer (NK) cells, the dominant leukocyte population exhibiting a unique phenotype, and fetal extravillous trophoblast which comes into direct contact with maternal decidual cells. To establish a successful placental development and healthy pregnancy outcome, the maternal immune system must tolerate paternal antigens expressed by trophoblast cells yet remain efficient for clearing any local pathogen infection. This review deals mainly with decidual NK cells. A key element, among others, to achieve such dual functions is the direct interaction between activating and inhibitory receptors expressed by decidual NK cells and their specific ligands presented by trophoblast or other decidual cells. Depending whether maternal decidual cells and trophoblast are infected by viruses, the balance between activating and inhibitory receptor signals mediated by decidual NK cell–trophoblast cross-talk results in tolerance (healthy pregnancy) or specific killing (pathogen-infected cells).
      PubDate: 2017-07-25T09:58:46Z
      DOI: 10.12688/f1000research.11690.1
      Issue No: Vol. 6 (2017)
       
  • Neuroimaging in aging: brain maintenance [version 1; referees: 2 approved]

    • Authors: Lars Nyberg
      Abstract: Neuroimaging studies of the aging brain provide support that the strongest predictor of preserved memory and cognition in older age is brain maintenance, or relative lack of brain pathology. Evidence for brain maintenance comes from different levels of examination, but up to now relatively few studies have used a longitudinal design. Examining factors that promote brain maintenance in aging is a critical task for the future and may be combined with the use of new techniques for multimodal imaging.
      PubDate: 2017-07-25T09:47:36Z
      DOI: 10.12688/f1000research.11419.1
      Issue No: Vol. 6 (2017)
       
  • Modern Neuraxial Anesthesia for Labor and Delivery [version 1; referees: 2
           approved]

    • Authors: Marie-Louise Meng, Richard Smiley
      Abstract: The availability of safe, effective analgesia during labor has become an expectation for women in most of the developed world over the past two or three decades. More than 60% of women in the United States now receive some kind of neuraxial procedure during labor. This article is a brief review of the advantages and techniques of neuraxial labor analgesia along with the recent advances and controversies in the field of labor analgesia. For the most part, we have aimed the discussion at the non-anesthesiologist to give other practitioners a sense of the state of the art and science of labor analgesia in the second decade of the 21st century.
      PubDate: 2017-07-25T08:45:33Z
      DOI: 10.12688/f1000research.11130.1
      Issue No: Vol. 6 (2017)
       
  • Glucocorticoid receptor action in metabolic and neuronal function [version
           1; referees: 3 approved]

    • Authors: Michael J. Garabedian, Charles A. Harris, Freddy Jeanneteau
      Abstract: Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.
      PubDate: 2017-07-24T14:14:24Z
      DOI: 10.12688/f1000research.11375.1
      Issue No: Vol. 6 (2017)
       
  • Pediatric hereditary angioedema: an update [version 1; referees: 2
           approved]

    • Authors: Geetika Sabharwal, Timothy Craig
      Abstract: Hereditary angioedema (HAE) with C1-inhibitor (C1-Inh) deficiency (C1-Inh-HAE) is a rare, life-threatening, and disabling genetic disorder characterized by self-limited tissue swelling caused by deficiency or dysfunction of C1-Inh. Our aim in this update is to discuss new advances in HAE therapy, focusing mainly on the various treatment options that have become available recently and also drugs that are under trial for prophylaxis to prevent attacks. There is a paradigm shift to where the treatment of HAE is headed, focusing now on prophylactic treatment rather than abortive management.
      PubDate: 2017-07-24T10:42:44Z
      DOI: 10.12688/f1000research.11320.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in molecular pathology of craniopharyngioma [version 1;
           referees: 2 approved]

    • Authors: Sarah Larkin, Niki Karavitaki
      Abstract: Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. Two major histological subtypes have been recognised, the papillary and the adamantinomatous. Craniopharyngiomas remain challenging tumours to manage and are associated with significant morbidities and mortality. Recent advances in the molecular pathology of these neoplasms have identified BRAF mutations in the papillary variant, offering promising options for targeted pharmacological treatment. The involvement of β-catenin and the Wnt pathway in the tumorigenesis of the adamantinomatous subtype has been previously established with the identification of stabilising mutations in exon 3 of CTNNB1. Further understanding of the pathogenesis of this subtype has been facilitated with the use of mouse models and xenograft experiments. It has been proposed that the clusters of cells with upregulated Wnt/β-catenin signalling induce tumour formation in a paracrine manner; the complex interactions occurring between different cell populations need to be further clarified for further expansion of this hypothesis. This review outlines recent key advances in our understanding of the molecular pathology of craniopharyngiomas and discusses some of the challenges that need to be overcome for the development of targeted therapies that will hopefully improve the management and the outcomes of these patients.
      PubDate: 2017-07-24T09:51:24Z
      DOI: 10.12688/f1000research.11549.1
      Issue No: Vol. 6 (2017)
       
  • Proteolytic processing of the L-type Ca2+ channel alpha11.2 subunit in
           neurons [version 1; referees: 2 approved]

    • Authors: Olivia R. Buonarati, Peter B. Henderson, Geoffrey G. Murphy, Mary C. Horne, Johannes W. Hell
      Abstract: Background: The L-type Ca2+ channel Cav1.2 is a prominent regulator of neuronal excitability, synaptic plasticity, and gene expression. The central element of Cav1.2 is the pore-forming α11.2 subunit. It exists in two major size forms, whose molecular masses have proven difficult to precisely determine. Recent work suggests that α11.2 is proteolytically cleaved between the second and third of its four pore-forming domains (Michailidis et al,. 2014). Methods: To better determine the apparent molecular masses (MR)of the α11.2 size forms, extensive systematic immunoblotting of brain tissue as well as full length and C-terminally truncated α11.2 expressed in HEK293 cells was conducted using six different region–specific antibodies against α11.2. Results: The full length form of α11.2 migrated, as expected, with an apparent MR of ~250 kDa. A shorter form of comparable prevalence with an apparent MR of ~210 kDa could only be detected in immunoblots probed with antibodies recognizing α11.2 at an epitope 400 or more residues upstream of the C-terminus. Conclusions: The main two size forms of α11.2 are the full length form and a shorter form, which lacks ~350 distal C-terminal residues. Midchannel cleavage as suggested by Michailidis et al. (2014) is at best minimal in brain tissue.
      PubDate: 2017-07-21T14:47:17Z
      DOI: 10.12688/f1000research.11808.1
      Issue No: Vol. 6 (2017)
       
  • New frontiers in metabolomics: from measurement to insight [version 1;
           referees: 3 approved]

    • Authors: Eli Riekeberg, Robert Powers
      Abstract: Metabolomics is the newest addition to the “omics” disciplines and has shown rapid growth in its application to human health research because of fundamental advancements in measurement and analysis techniques. Metabolomics has unique and proven advantages in systems biology and biomarker discovery. The next generation of analysis techniques promises even richer and more complete analysis capabilities that will enable earlier clinical diagnosis, drug refinement, and personalized medicine. A review of current advancements in methodologies and statistical analysis that are enhancing and improving the performance of metabolomics is presented along with highlights of some recent successful applications.
      PubDate: 2017-07-19T15:11:13Z
      DOI: 10.12688/f1000research.11495.1
      Issue No: Vol. 6 (2017)
       
  • Case Report: An incidentaloma that catches your eye - adrenal myelolipoma
           [version 1; referees: 2 approved]

    • Authors: Rosanna D'Addosio, Joselyn Rojas, Valmore Bermúdez, Flor Ledesma, Kyle Hoedebecke
      Abstract: Background: Adrenal incidentaloma refers to the incidental finding of a tumor in the adrenal gland, where nonfunctional forms are the most common variant. Myelolipoma is a rare (0.08-0.4%) occurrence characterized by adipose and hematopoietic tissue. The aim of this case report is to describe the diagnosis and appropriate management of a myelolipoma in an asymptomatic patient, which was originally considered an incidental hepatic hemangioma prior to being identified as a giant adrenal adenoma. Case description: The patient was a 54 year old obese female with a recent diagnosis of diabetes type II and dyslipidemia with recent ultrasound imaging suggestive of a hepatic hemangioma. An MRI was performed revealing a 7x6cm lesion in the right adrenal area indicating a giant adrenal adenoma. An adrenalectomy was performed without complications. The pathology report identified a myelolipoma. Discussion: The incidence of myelolipoma has recently increased due to advances in radiological techniques. Its etiology is unclear and the most accepted theories support a myeloid cell metaplasia in the embryonic stage as a result of stress, infections, or adrenocorticotropic hormone or erythropoietin stimulus. Contributing components may include bone morphogenetic protein 2 and β-catenin, as well as the presence of the chromosomal translocation (3, 21) (q25; p11). Despite its benign nature, the association with other adrenal lipomas must be ruled out. A biochemical evaluation is essential for detecting subclinical states, such as Cushing syndrome and pheochromocytoma. Conclusion: Adrenal myelolipomas are rare benign tumors that are generally asymptomatic. Uncertainty still exists surrounding their etiology. Surgical management depends on hormone production, tumor size, high risk features on imaging and patient consent.  Additional information is needed to better understand myelolipomas, their etiology, and clinical management.  Incidentalomas may confuse the physician and patient. Ensuring proper multidisciplinary management based on the clinical guidelines of endocrinology allowed a satisfactory resolution of this case.
      PubDate: 2017-07-18T16:04:37Z
      DOI: 10.12688/f1000research.11766.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in the prevention of preterm birth [version 1; referees: 2
           approved]

    • Authors: Jeff A Keelan, John P Newnham
      Abstract: Preterm birth (PTB) remains a major obstetric healthcare problem and a significant contributor to perinatal morbidity, mortality, and long-term disability. Over the past few decades, the perinatal outcomes of preterm neonates have improved markedly through research and advances in neonatal care, whereas rates of spontaneous PTB have essentially remained static. However, research into causal pathways and new diagnostic and treatment modalities is now bearing fruit and translational initiatives are beginning to impact upon PTB rates. Successful PTB prevention requires a multifaceted approach, combining public health and educational programs, lifestyle modification, access to/optimisation of obstetric healthcare, effective prediction and diagnostic modalities, and the application of effective, targeted interventions. Progress has been made in some of these areas, although there remain areas of controversy and uncertainty. Attention is now being directed to areas where greater gains can be achieved. In this mini-review, we will briefly and selectively review a range of PTB prevention strategies and initiatives where progress has been made and where exciting opportunities await exploitation, evaluation, and implementation.
      PubDate: 2017-07-18T15:17:25Z
      DOI: 10.12688/f1000research.11385.1
      Issue No: Vol. 6 (2017)
       
  • Diagnostic approach to pleural diseases: new tricks for an old trade
           [version 1; referees: 2 approved]

    • Authors: Fabien Maldonado, Robert J. Lentz, Richard W. Light
      Abstract: The burden of pleural diseases has substantially increased in the past decade because of a rise in the incidence of pleural space infections and pleural malignancies in a patient population that is older and more immunocompromised and has more comorbidities. This complexity increasingly requires minimally invasive diagnostic options and tailored management. Implications for patients are such that the limitations of current diagnostic methods need to be addressed by multidisciplinary teams of investigators from the fields of imaging, biology, and engineering. Ignored for a long time as an epiphenomenon at the crossroad of many unrelated medical problems, pleural diseases are finally getting the attention they deserve and have spurred a vibrant and exciting field of research.
      PubDate: 2017-07-17T13:48:20Z
      DOI: 10.12688/f1000research.11646.1
      Issue No: Vol. 6 (2017)
       
  • Serum complexed and free prostate specific antigen levels are lower in
           female elite athletes in comparison to control women [version 1; referees:
           2 approved]

    • Authors: Emma Eklund, Eleftherios P Diamandis, Carla Muytjens, Sarah Wheeler, Anu Mathew, Martin Stengelin, Eli Glezer, Galina Nikolenko, Marshall D. Brown, Yingye Zheng, Angelica Lindén Hirschberg
      Abstract: Background: We hypothesize that prostate specific antigen (PSA), a protein that it is under regulation by androgens, may be differentially expressed in female elite athletes in comparison to control women. Methods: We conducted a cross-sectional study of 106 female athletes and 114 sedentary age-matched controls.  Serum from these women was analyzed for complexed prostate specific antigen (cPSA) and free prostate specific antigen (fPSA), by fifth generation assays with limits of detection of around 6 and 140 fg/mL, respectively.  A panel of estrogens, androgens and progesterone in the same serum was also quantified by tandem mass spectrometry.  Results: Both components of serum PSA (cPSA and fPSA) were lower in the elite athletes vs the control group (P=0.033 and 0.013, respectively).  Furthermore, estrone (p=0.003) and estradiol (p=0.004) were significantly lower, and dehydroepiandrosterone  (p=0.095) and 5-androstene-3β, 17β-diol (p=0.084) tended to be higher in the athletes vs controls. Oral contraceptive use was similar between groups and significantly associated with increased cPSA and fPSA in athletes (p= 0.046 and 0.009, respectively).  PSA fractions were not significantly associated with progesterone changes. The Spearman correlation between cPSA and fPSA in both athletes and controls was 0.75 (P < 0.0001) and 0.64 (P < 0.0001), respectively.  Conclusions: Elite athletes have lower complexed and free PSA, higher levels of androgen precursors and lower levels of estrogen in their serum than sedentary control women. Abbreviations: cPSA, complexed PSA; fPSA, free PSA; PCOS, polycystic ovarian syndrome; E1, estrone; E2, estradiol; DHEA, dehydroepiandrosterone, Testo, testosterone; DHT, dihydrotestosterone; PROG, progesterone; Delta 4, androstenedione; Delta 5, androst-5-ene-3β, 17β-diol; BMD, body mineral density; LLOQ, lower limit of quantification; ULOQ, upper limit of quantification; LOD, limit of detection; ACT, α1-antichymotrypsin
      PubDate: 2017-07-17T10:31:06Z
      DOI: 10.12688/f1000research.11821.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in understanding Listeria monocytogenes infection: the
           importance of subcellular and physiological context [version 1; referees:
           3 approved]

    • Authors: Daryl J. V. David, Pascale Cossart
      Abstract: The bacterial pathogen Listeria monocytogenes (Lm) is the causative agent of listeriosis, a rare but fatal foodborne disease. During infection, Lm can traverse several host barriers and enter the cytosol of a variety of cell types. Thus, consideration of the extracellular and intracellular niches of Lm is critical for understanding the infection process. Here, we review advances in our understanding of Lm infection and highlight how the interactions between the host and the pathogen are context dependent. We discuss discoveries of how Lm senses entry into the host cell cytosol. We present findings concerning how the nature of the various cytoskeleton components subverted by Lm changes depending on both the stage of infection and the subcellular context. We present discoveries of critical components required for Lm traversal of physiological barriers. Interactions between the host gut microbiota and Lm will be briefly discussed. Finally, the importance of Lm biodiversity and post-genomics approaches as a promising way to discover novel virulence factors will be highlighted.
      PubDate: 2017-07-13T15:58:27Z
      DOI: 10.12688/f1000research.11363.1
      Issue No: Vol. 6 (2017)
       
  • Coronary CT angiography in acute chest pain [version 1; referees: 3
           approved]

    • Authors: Nikhil Goyal, Arthur Stillman
      Abstract: Coronary computed tomographic angiography has become a reliable diagnostic tool in the evaluation of patients with chest pain. Studies have shown this modality to be accurate and safe when compared with conventional methods of assessing patients with chest pain. We review the recent developments with coronary computed tomographic angiography and devote particular attention toward its application to triage patients in the emergency department.
      PubDate: 2017-07-13T15:27:07Z
      DOI: 10.12688/f1000research.11250.1
      Issue No: Vol. 6 (2017)
       
  • Progress toward an integrated understanding of Parkinson’s disease
           [version 1; referees: 2 approved]

    • Authors: Maxime W.C. Rousseaux, Joshua M. Shulman, Joseph Jankovic
      Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting over 10 million individuals worldwide. While numerous effective symptomatic treatments are currently available, no curative or disease-modifying therapies exist. An integrated, comprehensive understanding of PD pathogenic mechanisms will likely address this unmet clinical need. Here, we highlight recent progress in PD research with an emphasis on promising translational findings, including (i) advances in our understanding of disease susceptibility, (ii) improved knowledge of cellular dysfunction, and (iii) insights into mechanisms of spread and propagation of PD pathology. We emphasize connections between these previously disparate strands of PD research and the development of an emerging systems-level understanding that will enable the next generation of PD therapeutics.
      PubDate: 2017-07-12T13:24:38Z
      DOI: 10.12688/f1000research.11820.1
      Issue No: Vol. 6 (2017)
       
  • Chronic urticaria: a focus on pathogenesis [version 1; referees: 3
           approved]

    • Authors: Riccardo Asero, Alberto Tedeschi, Angelo Valerio Marzano, Massimo Cugno
      Abstract: Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients’ quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder.
      PubDate: 2017-07-11T09:22:19Z
      DOI: 10.12688/f1000research.11546.1
      Issue No: Vol. 6 (2017)
       
  • Recent advances in understanding eosinophil biology [version 1; referees:
           2 approved]

    • Authors: Amy Klion
      Abstract: With the advent of novel therapies targeting eosinophils, there has been renewed interest in understanding the basic biology of this unique cell. In this context, murine models and human studies have continued to highlight the role of the eosinophil in homeostatic functions and immunoregulation. This review will focus on recent advances in our understanding of eosinophil biology that are likely to have important consequences on the development and consequences of eosinophil-targeted therapies. Given the breadth of the topic, the discussion will be limited to three areas of interest: the eosinophil life cycle, eosinophil heterogeneity, and mechanisms of cell-cell communication.
      PubDate: 2017-07-07T15:21:45Z
      DOI: 10.12688/f1000research.11133.1
      Issue No: Vol. 6 (2017)
       
  • Protein sites with more coevolutionary connections tend to evolve slower,
           while more variable protein families acquire higher coevolutionary
           connections [version 2; referees: 2 approved]

    • Authors: Sapan Mandloi, Saikat Chakrabarti
      Abstract: Background: Amino acid exchanges within proteins sometimes compensate for one another and could therefore be co-evolved. It is essential to investigate the intricate relationship between the extent of coevolution and the evolutionary variability exerted at individual protein sites, as well as the whole protein. Methods: In this study, we have used a reliable set of coevolutionary connections (sites within 10Å spatial distance) and investigated their correlation with the evolutionary diversity within the respective protein sites. Results: Based on our observations, we propose an interesting hypothesis that higher numbers of coevolutionary connections are associated with lesser evolutionary variable protein sites, while higher numbers of the coevolutionary connections can be observed for a protein family that has higher evolutionary variability. Our findings also indicate that highly coevolved sites located in a solvent accessible state tend to be less evolutionary variable. This relationship reverts at the whole protein level where cytoplasmic and extracellular proteins show moderately higher anti-correlation between the number of coevolutionary connections and the average evolutionary conservation of the whole protein. Conclusions: Observations and hypothesis presented in this study provide intriguing insights towards understanding the critical relationship between coevolutionary and evolutionary changes observed within proteins. Our observations encourage further investigation to find out the reasons behind subtle variations in the relationship between coevolutionary connectivity and evolutionary diversity for proteins located at various cellular localizations and/or involved in different molecular-biological functions.
      PubDate: 2017-07-07T14:04:19Z
      DOI: 10.12688/f1000research.11251.2
      Issue No: Vol. 6 (2017)
       
  • Developing a strategy for computational lab skills training through
           Software and Data Carpentry: Experiences from the ELIXIR Pilot action
           [version 1; referees: 3 approved]

    • Authors: Aleksandra Pawlik, Celia W.G. van Gelder, Aleksandra Nenadic, Patricia M. Palagi, Eija Korpelainen, Philip Lijnzaad, Diana Marek, Susanna-Assunta Sansone, John Hancock, Carole Goble
      Abstract: Quality training in computational skills for life scientists is essential to allow them to deliver robust, reproducible and cutting-edge research. A pan-European bioinformatics programme, ELIXIR, has adopted a well-established and progressive programme of computational lab and data skills training from Software and Data Carpentry, aimed at increasing the number of skilled life scientists and building a sustainable training community in this field. This article describes the Pilot action, which introduced the Carpentry training model to the ELIXIR community.
      PubDate: 2017-07-03T15:16:10Z
      DOI: 10.12688/f1000research.11718.1
      Issue No: Vol. 6 (2017)
       
  • Service evaluation of the implementation of a digitally-enabled care
           pathway for the recognition and management of acute kidney injury [version
           1; referees: 2 approved]

    • Authors: Alistair Connell, Hugh Montgomery, Stephen Morris, Claire Nightingale, Sarah Stanley, Mary Emerson, Gareth Jones, Omid Sadeghi-Alavijeh, Charles Merrick, Dominic King, Alan Karthikesalingam, Cian Hughes, Joseph Ledsam, Trevor Back, Geraint Rees, Rosalind Raine, Christopher Laing
      Abstract: Acute Kidney Injury (AKI), an abrupt deterioration in kidney function, is defined by changes in urine output or serum creatinine. AKI is common (affecting up to 20% of acute hospital admissions in the United Kingdom), associated with significant morbidity and mortality, and expensive (excess costs to the National Health Service in England alone may exceed £1 billion per year). NHS England has mandated the implementation of an automated algorithm to detect AKI based on changes in serum creatinine, and to alert clinicians. It is uncertain, however, whether ‘alerting’ alone improves care quality.   We have thus developed a digitally-enabled care pathway as a clinical service to inpatients in the Royal Free Hospital (RFH), a large London hospital. This pathway incorporates a mobile software application - the “Streams-AKI” app, developed by DeepMind Health - that applies the NHS AKI algorithm to routinely collected serum creatinine data in hospital inpatients. Streams-AKI alerts clinicians to potential AKI cases, furnishing them with a trend view of kidney function alongside other relevant data, in real-time, on a mobile device. A clinical response team comprising nephrologists and critical care nurses responds to these AKI alerts by reviewing individual patients and administering interventions according to existing clinical practice guidelines.   We propose a mixed methods service evaluation of the implementation of this care pathway. This evaluation will assess how the care pathway meets the health and care needs of service users (RFH inpatients), in terms of clinical outcome, processes of care, and NHS costs. It will also seek to assess acceptance of the pathway by members of the response team and wider hospital community. All analyses will be undertaken by the service evaluation team from UCL (Department of Applied Health Research) and St George’s, University of London (Population Health Research Institute).
      PubDate: 2017-06-30T14:24:00Z
      DOI: 10.12688/f1000research.11637.1
      Issue No: Vol. 6 (2017)
       
  • TIDDIT, an efficient and comprehensive structural variant caller for
           massive parallel sequencing data [version 2; referees: 2 approved]

    • Authors: Jesper Eisfeldt, Francesco Vezzi, Pall Olason, Daniel Nilsson, Anna Lindstrand
      Abstract: Reliable detection of large structural variation ( > 1000 bp) is important in both rare and common genetic disorders. Whole genome sequencing (WGS) is a technology that may be used to identify a large proportion of the genomic structural variants (SVs) in an individual in a single experiment. Even though SV callers have been extensively used in research to detect mutations, the potential usage of SV callers within routine clinical diagnostics is still limited. One well known, but not well-addressed problem is the large number of benign variants and reference errors present in the human genome that further complicates analysis. Even though there is a wide range of SV-callers available, the number of callers that allow detection of the entire spectra of SV at a low computational cost is still relatively limited.
      PubDate: 2017-06-30T10:09:21Z
      DOI: 10.12688/f1000research.11168.2
      Issue No: Vol. 6 (2017)
       
  • Lumboperitoneal shunt insertion without fluoroscopy guidance: Accuracy of
           placement in a series of 107 procedures [version 2; referees: 1 approved,
           2 approved with reservations]

    • Authors: Sabah Al-Rashed, Haider Kareem, Neeraj Kalra, Linda D’Antona, Mouness Obeidat, Bhavesh Patel, Ahmed Toma
      Abstract: Background: Lumboperitoneal (LP) shunts were the mainstay of cerebrospinal fluid diversion therapy for idiopathic intracranial hypertension (IIH). The traditionally cited advantage of LP shunts over ventriculoperitoneal (VP) shunts is the ease of insertion in IIH. This needs to be placed at the level of L3/4 to be below the level of the spinal cord. The objective of this study was to analyse the position of LP shunts inserted without portable fluoroscopy guidance. Methods: A retrospective analysis of radiology was performed for patients who underwent lumboperitoneal shunts between 2006 and 2016 at the National Hospital for Neurology and Neurosurgery. Patients who had insertion of a LP shunt without fluoroscopy guidance were selected.  Patients without post-procedural imaging were excluded. A retrospective analysis of the clinical notes was also performed. Results: Between 2006 and 2016, 163 lumboperitoneal shunts were inserted in 105 patients. A total of 56 cases were excluded due to lack of post-procedural imaging; therefore, 107 post-procedural x-rays were reviewed. In 17 (15.8%) cases the proximal end of the LP shunt was placed at L1/L2 level or above. Conclusions: Insertion of LP shunts without portable fluoroscopy guidance gives a 15.8% risk of incorrect positioning of the proximal end of the catheter. We suggest that x-ray is recommended to avoid incorrect level placement. Further investigation could be carried out with a control group with fluoroscopy against patients without.
      PubDate: 2017-06-30T08:53:51Z
      DOI: 10.12688/f1000research.11089.2
      Issue No: Vol. 6 (2017)
       
  • valr: Reproducible genome interval analysis in R [version 1; referees: 2
           approved]

    • Authors: Kent A. Riemondy, Ryan M. Sheridan, Austin Gillen, Yinni Yu, Christopher G. Bennett, Jay R. Hesselberth
      Abstract: New tools for reproducible exploratory data analysis of large datasets are important to address the rising size and complexity of genomic data. We developed the valr R package to enable flexible and efficient genomic interval analysis. valr leverages new tools available in the ”tidyverse”, including dplyr. Benchmarks of valr show it performs similar to BEDtools and can be used for interactive analyses and incorporated into existing analysis pipelines.
      PubDate: 2017-06-29T13:18:54Z
      DOI: 10.12688/f1000research.11997.1
      Issue No: Vol. 6 (2017)
       
  • What do hypnotics cost hospitals and healthcare' [version 2; referees:
           2 approved]

    • Authors: Daniel F. Kripke
      Abstract: Hypnotics (sleeping pills) are prescribed widely, but the economic costs of the harm they have caused have been largely unrecognized. Randomized clinical trials have observed that hypnotics increase the incidence of infections. Likewise, hypnotics increase the incidence of major depression and cause emergency admissions for overdoses and deaths.  Epidemiologically, hypnotic use is associated with cancer, falls, automobile accidents, and markedly increased overall mortality.  This article considers the costs to hospitals and healthcare payers of hypnotic-induced infections and other severe consequences of hypnotic use. These are a probable cause of excessive hospital admissions, prolonged lengths of stay at increased costs, and increased readmissions. Accurate information is scanty, for in-hospital hypnotic benefits and risks have scarcely been studied -- certainly not the economic costs of inpatient adverse effects.  Healthcare costs of outpatient adverse effects likewise need evaluation. In one example, use of hypnotics among depressed patients was strongly associated with higher healthcare costs and more short-term disability. A best estimate is that U.S. costs of hypnotic harms to healthcare systems are on the order of $55 billion, but conceivably might be as low as $10 billion or as high as $100 billion. More research is needed to more accurately assess unnecessary and excessive hypnotics costs to providers and insurers, as well as financial and health damages to the patients themselves.
      PubDate: 2017-06-28T10:13:54Z
      DOI: 10.12688/f1000research.11328.2
      Issue No: Vol. 6 (2017)
       
  • Monitoring respiration and oxygen saturation in patients during the first
           night after elective bariatric surgery: A cohort study [version 2;
           referees: 2 approved]

    • Authors: Liselott Wickerts, Sune Forsberg, Frederic Bouvier, Jan Jakobsson
      Abstract: Background: Obstructive sleep apnoea and obese hypoventilation is not uncommon in patients with obesity. Residuals effect from surgery/anaesthesia and opioid analgesics may worsen respiration during the first nights after bariatric surgery. The aim of this observational study was to monitor respiration on the first postoperative night following elective bariatric surgery. Methods: This observational study aimed to determine the incidence and severity of hypo/apnoea in low risk obsess patients undergoing elective bariatric surgery in general anesthaesia. Patients with known or suspected sleep respiratory disturbances was not included. ESS was scored prior to surgery. Oxygen desaturation was analyzed by continuous respiratory monitoring. Mean oxygen saturation (SpO2), nadir SPo2, apnoea/hypopnea index and oxygen desaturation index was assess by standard tools. Results: 45 patients were monitored with portable polygraphy equipment (Embletta, ResMed) during the first postoperative night at the general ward following elective laparoscopic bariatric surgery. The prop ESS was 0-5 in 22, 6-10 in 14 and 11-16 in 6 of the patients studied (missing data 3). Mean SpO2 was 93%; 10 patients had a mean SpO2 of less than 92% and 4 of less than 90%. The lowest mean SpO2 was 87%. There were 16 patients with a nadir SpO2 of less than 85%, lowest nadir SpO2 being 63%. An Apnoea Hypo/apnoea Index (AHI) > 5 was found in 2 patients only (AHI 10 and 6), and an Oxygen Desaturation index (ODI) > 5 was found in 3 patients (24, 10 and 6, respectively). 3 patients had more prolonged (> 30 seconds) apnoea with nadir SpO2 81%, 83% and 86%. ESS score and type of surgery did not impact on respiration/oxygenation during the observation period. Conclusions: A low mean SpO2 and episodes of desaturation were not uncommon during the first postoperative night following elective bariatric surgery in patients without history of night time breathing disturbance. AHI and/or ODI of more than 5 were only rarely seen. Night-time respiration monitoring provided seemingly sparse additional information. Further studies are need to assess risk factors and potential impact of the desaturation episodes that occurs during sleep.
      PubDate: 2017-06-23T08:11:46Z
      DOI: 10.12688/f1000research.11519.2
      Issue No: Vol. 6 (2017)
       
  • ELIXIR-UK role in bioinformatics training at the national level and across
           ELIXIR [version 1; referees: 2 approved, 1 approved with reservations]

    • Authors: L. Larcombe, R. Hendricusdottir, T.K. Attwood, F. Bacall, N. Beard, L.J. Bellis, W.B. Dunn, J.M. Hancock, A. Nenadic, C. Orengo, B. Overduin, S-A Sansone, M. Thurston, M.R. Viant, C.L. Winder, C.A. Goble, C.P. Ponting, G. Rustici
      Abstract: ELIXIR-UK is the UK node of ELIXIR, the European infrastructure for life science data. Since its foundation in 2014, ELIXIR-UK has played a leading role in training both within the UK and in the ELIXIR Training Platform, which coordinates and delivers training across all ELIXIR members. ELIXIR-UK contributes to the Training Platform’s coordination and supports the development of training to address key skill gaps amongst UK scientists. As part of this work it acts as a conduit for nationally-important bioinformatics training resources to promote their activities to the ELIXIR community. ELIXIR-UK also leads ELIXIR’s flagship Training Portal, TeSS, which collects information about a diverse range of training and makes it easily accessible to the community. ELIXIR-UK also works with others to provide key digital skills training, partnering with the Software Sustainability Institute to provide Software Carpentry training to the ELIXIR community and to establish the Data Carpentry initiative, and taking a lead role amongst national stakeholders to deliver the StaTS project – a coordinated effort to drive engagement with training in statistics.
      PubDate: 2017-06-21T14:36:22Z
      DOI: 10.12688/f1000research.11837.1
      Issue No: Vol. 6 (2017)
       
  • Comprehensive comparison of Pacific Biosciences and Oxford Nanopore
           Technologies and their applications to transcriptome analysis [version 2;
           referees: 2 approved]

    • Authors: Jason L Weirather, Mariateresa de Cesare, Yunhao Wang, Paolo Piazza, Vittorio Sebastiano, Xiu-Jie Wang, David Buck, Kin Fai Au
      Abstract: Background: Given the demonstrated utility of Third Generation Sequencing [Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT)] long reads in many studies, a comprehensive analysis and comparison of their data quality and applications is in high demand. Methods: Based on the transcriptome sequencing data from human embryonic stem cells, we analyzed multiple data features of PacBio and ONT, including error pattern, length, mappability and technical improvements over previous platforms. We also evaluated their application to transcriptome analyses, such as isoform identification and quantification and characterization of transcriptome complexity, by comparing the performance of size-selected PacBio, non-size-selected ONT and their corresponding Hybrid-Seq strategies (PacBio+Illumina and ONT+Illumina). Results: PacBio shows overall better data quality, while ONT provides a higher yield. As with data quality, PacBio performs marginally better than ONT in most aspects for both long reads only and Hybrid-Seq strategies in transcriptome analysis. In addition, Hybrid-Seq shows superior performance over long reads only in most transcriptome analyses. Conclusions: Both PacBio and ONT sequencing are suitable for full-length single-molecule transcriptome analysis. As this first use of ONT reads in a Hybrid-Seq analysis has shown, both PacBio and ONT can benefit from a combined Illumina strategy. The tools and analytical methods developed here provide a resource for future applications and evaluations of these rapidly-changing technologies.
      PubDate: 2017-06-19T14:13:17Z
      DOI: 10.12688/f1000research.10571.2
      Issue No: Vol. 6 (2017)
       
  • A very simple, re-executable neuroimaging publication [version 2;
           referees: 1 approved, 2 approved with reservations]

    • Authors: Satrajit S. Ghosh, Jean-Baptiste Poline, David B. Keator, Yaroslav O. Halchenko, Adam G. Thomas, Daniel A. Kessler, David N. Kennedy
      Abstract: Reproducible research is a key element of the scientific process. Re-executability of neuroimaging workflows that lead to the conclusions arrived at in the literature has not yet been sufficiently addressed and adopted by the neuroimaging community. In this paper, we document a set of procedures, which include supplemental additions to a manuscript, that unambiguously define the data, workflow, execution environment and results of a neuroimaging analysis, in order to generate a verifiable re-executable publication. Re-executability provides a starting point for examination of the generalizability and reproducibility of a given finding.
      PubDate: 2017-06-15T13:26:30Z
      DOI: 10.12688/f1000research.10783.2
      Issue No: Vol. 6 (2017)
       
  • Insights for conducting real-time focus groups online using a web
           conferencing service [version 2; referees: 2 approved]

    • Authors: James Kite, Philayrath Phongsavan
      Abstract: Background: Online focus groups have been increasing in use over the last 2 decades, including in biomedical and health-related research. However, most of this research has made use of text-based services such as email, discussion boards, and chat rooms that do not replicate the experience of face-to-face focus groups. Web conferencing services have the potential to more closely match the face-to-face focus group experience, including important visual and aural cues. This paper provides critical reflections on using a web conferencing service to conduct online focus groups. Methods: We conducted both online and face-to-face focus groups as part of the same study. The online groups were conducted in real-time using the web conferencing service, Blackboard Collaborate TM. We used reflective practice to assess the similarities and differences in the conduct and content of the groups across the two platforms. Results: We found that further research using such services is warranted, particularly when working with hard-to-reach or geographically dispersed populations. The level of discussion and the quality of the data obtained was similar to that found in face-to-face groups. However, some issues remain, particularly in relation to managing technical issues experienced by participants and ensuring adequate recording quality to facilitate transcription and analysis. Conclusions: Our experience with using web conferencing for online focus groups suggests that they have the potential to offer a realistic and comparable alternative to face-to-face focus groups, especially for geographically dispersed populations such as rural and remote health practitioners. Further testing of these services is warranted but researchers should carefully consider the service they use to minimise the impact of technical difficulties.
      PubDate: 2017-06-12T09:52:50Z
      DOI: 10.12688/f1000research.10427.2
      Issue No: Vol. 6 (2017)
       
  • Platelet distribution width, mean platelet volume and haematological
           parameters in patients with uncomplicated plasmodium falciparum and P.
           vivax malaria [version 1; referees: 1 approved, 2 approved with
           reservations]

    • Authors: Elrazi A. Ali, Tajeldin M. Abdalla, Ishag Adam
      Abstract: Background: The association between the haematological profile (including abnormal platelets) and malaria is not completely understood. There are few published data on haematological profiles of malaria patients in areas with unstable malaria transmission. The current study was conducted to investigate if the haematological parameters, including platelet indices, were reliable predictors for microscopically-diagnosed malaria infection. Methods: A case-control study with a total of 324 participants (162 in each arm) was conducted at the out-patient clinic of New Halfa hospital during the rainy and post rainy season (August 2014 through to January 2015). The cases were patients with uncomplicated Plasmodium falciparum (107; 66.9%) and P. vivax malaria (55, 34.0%) infections. The controls were aparasitemic individuals. The haematological parameters were investigated using an automated hemo-analyser. Results: There was no significant difference in the mean (±SD) age between the study groups; however, compared to the controls, patients with uncomplicated malaria had significantly lower haemoglobin, leucocyte and platelet counts, and significantly higher red cell distribution width (RDW), platelet distribution width (PDW) and mean platelet volume (MPV). Conclusions: The study revealed that among the haematological indices, PDW and MPV were the main predictors for uncomplicated P. falciparum and P. vivax malaria infection. Abbreviations: OR: odds ratio.
      PubDate: 2017-06-12T08:58:36Z
      DOI: 10.12688/f1000research.11767.1
      Issue No: Vol. 6 (2017)
       
  • MinION Analysis and Reference Consortium: Phase 2 data release and
           analysis of R9.0 chemistry [version 1; referees: 1 approved, 2 approved
           with reservations]

    • Authors: Miten Jain, John R. Tyson, Matthew Loose, Camilla L.C. Ip, David A. Eccles, Justin O'Grady, Sunir Malla, Richard M. Leggett, Ola Wallerman, Hans J. Jansen, Vadim Zalunin, Ewan Birney, Bonnie L. Brown, Terrance P. Snutch, Hugh E. Olsen, MinION Analysis; Reference Consortium
      Abstract: Background: Long-read sequencing is rapidly evolving and reshaping the suite of opportunities for genomic analysis. For the MinION in particular, as both the platform and chemistry develop, the user community requires reference data to set performance expectations and maximally exploit third-generation sequencing. We performed an analysis of MinION data derived from whole genome sequencing of Escherichia coli K-12 using the R9.0 chemistry, comparing the results with the older R7.3 chemistry. Methods: We computed the error-rate estimates for insertions, deletions, and mismatches in MinION reads. Results: Run-time characteristics of the flow cell and run scripts for R9.0 were similar to those observed for R7.3 chemistry, but with an 8-fold increase in bases per second (from 30 bps in R7.3 and SQK-MAP005 library preparation, to 250 bps in R9.0) processed by individual nanopores, and less drop-off in yield over time. The 2-dimensional (“2D”) N50 read length was unchanged from the prior chemistry. Using the proportion of alignable reads as a measure of base-call accuracy, 99.9% of “pass” template reads from 1-dimensional (“1D”)  experiments were mappable and ~97% from 2D experiments. The median identity of reads was ~89% for 1D and ~94% for 2D experiments. The total error rate (miscall + insertion + deletion ) decreased for 2D “pass” reads from 9.1% in R7.3 to 7.5% in R9.0 and for template “pass” reads from 26.7% in R7.3 to 14.5% in R9.0. Conclusions: These Phase 2 MinION experiments serve as a baseline by providing estimates for read quality, throughput, and mappability. The datasets further enable the development of bioinformatic tools tailored to the new R9.0 chemistry and the design of novel biological applications for this technology. Abbreviations: K: thousand, Kb: kilobase (one thousand base pairs), M: million, Mb: megabase (one million base pairs), Gb: gigabase (one billion base pairs).
      PubDate: 2017-05-31T14:15:00Z
      DOI: 10.12688/f1000research.11354.1
      Issue No: Vol. 6 (2017)
       
  • Case Report: Multiple hemorrhagic metastases to the brain from primary
           lung choriocarcinoma [version 1; referees: 2 approved]

    • Authors: Sunil Munakomi
      Abstract: Herein we report a very rare entity of multiple hemorrhagic metastases to the brain from a primary lung choriocarcinoma in a young woman. The patient presented with recent onset of progressive headache, decreased level of consciousness and multiple episodes of vomiting. CT of the head revealed multiple hemorrhagic lesions within the brain. The patient’s serum B-human chorionic gonadotrophin was increased.  A chest X-ray revealed a right lung mass. The patient urgently underwent operative excision of the lesion in the posterior fossa, so as to prevent impending tonsillar herniation. The histology from the lesion provided the diagnosis of choriocarcinoma. After surgery, ultrasonography of the abdomen and pelvis was normal, and a chest CT revealed an enhanced and highly vascular right apical lung lesion, suggestive of lung primary choriocarcinoma, with regard to the clinical background. The patient was then started on chemotherapy, following which her serum B-HCG level decreased rapidly. This case highlights the importance of keeping this entity in the differential diagnosis of hemorrhagic lesions in any patients of a child bearing age. Early diagnosis and rapid initiation of multimodal therapy is prudent for ensuring a good outcome from an otherwise rapidly metastasizing and highly vascular lesion.
      PubDate: 2017-05-23T15:07:38Z
      DOI: 10.12688/f1000research.11681.1
      Issue No: Vol. 6 (2017)
       
  • Case Report: Using ultrasound to prevent a broken catheter from migrating
           to the heart. [version 1; referees: 2 approved]

    • Authors: Pieter J. Schraverus, Suzanne van Rijswijk, Pieter Roel Tuinman
      Abstract: Peripheral intravenous (IV) catheters can break off while still in the patient, with possible detrimental effects such as upstream migration to the heart. These catheters have probably been damaged by the needle during a difficult insertion. A peripheral IV catheter was removed in a 90 year old patient and only half of the catheter was retrieved. By using ultrasound examination the remaining part of the IV catheter was identified, and retrieved surgically, before it could migrate towards the heart. This case report suggests that ultrasound should not only be used for difficult placement of a peripheral IV catheter, but can also be used when removal is complicated.
      PubDate: 2017-05-03T09:06:19Z
      DOI: 10.12688/f1000research.11206.1
      Issue No: Vol. 6 (2017)
       
  • Extending TCGA queries to automatically identify analogous genomic data
           from dbGaP [version 1; referees: 2 approved, 1 approved with reservations]
           

    • Authors: Erin K. Wagner, Satyajeet Raje, Liz Amos, Jessica Kurata, Abhijit S. Badve, Yingquan Li, Ben Busby
      Abstract: Data sharing is critical to advance genomic research by reducing the demand to collect new data by reusing and combining existing data and by promoting reproducible research. The Cancer Genome Atlas (TCGA) is a popular resource for individual-level genotype-phenotype cancer related data. The Database of Genotypes and Phenotypes (dbGaP) contains many datasets similar to those in TCGA. We have created a software pipeline that will allow researchers to discover relevant genomic data from dbGaP, based on matching TCGA metadata. The resulting research provides an easy to use tool to connect these two data sources.
      PubDate: 2017-03-24T14:42:12Z
      DOI: 10.12688/f1000research.9837.1
      Issue No: Vol. 6 (2017)
       
  • Resistance mechanisms to drug therapy in breast cancer and other solid
           tumors: An opinion [version 1; referees: 2 approved, 1 approved with
           reservations]

    • Authors: Fedor Moiseenko, Nikita Volkov, Alexey Bogdanov, Michael Dubina, Vladimir Moiseyenko
      Abstract: Cancer is an important contributor to mortality worldwide. Breast cancer is the most common solid tumor in women. Despite numerous drug combinations and regimens, all patients with advanced breast cancer, similarly to other solid tumors, inevitably develop resistance to treatment. Identified mechanisms of resistance could be classified into intra- and extracellular mechanisms. Intracellular mechanisms include drug metabolism and efflux, target modulations and damage restoration. Extracellular mechanisms might be attributed to the crosstalk between tumor cells and environmental factors. However, current knowledge concerning resistance mechanisms cannot completely explain the phenomenon of multi-drug resistance, which occurs in the vast majority of patients treated with chemotherapy. In this opinion article, we investigate the role of these factors in the development of drug-resistance.
      PubDate: 2017-03-17T15:25:07Z
      DOI: 10.12688/f1000research.10992.1
      Issue No: Vol. 6 (2017)
       
  • GeneBreak: detection of recurrent DNA copy number aberration-associated
           chromosomal breakpoints within genes [version 2; referees: 2 approved]

    • Authors: Evert van den Broek, Stef van Lieshout, Christian Rausch, Bauke Ylstra, Mark A. van de Wiel, Gerrit A. Meijer, Remond J.A. Fijneman, Sanne Abeln
      Abstract: Development of cancer is driven by somatic alterations, including numerical and structural chromosomal aberrations. Currently, several computational methods are available and are widely applied to detect numerical copy number aberrations (CNAs) of chromosomal segments in tumor genomes. However, there is lack of computational methods that systematically detect structural chromosomal aberrations by virtue of the genomic location of CNA-associated chromosomal breaks and identify genes that appear non-randomly affected by chromosomal breakpoints across (large) series of tumor samples. ‘GeneBreak’ is developed to systematically identify genes recurrently affected by the genomic location of chromosomal CNA-associated breaks by a genome-wide approach, which can be applied to DNA copy number data obtained by array-Comparative Genomic Hybridization (CGH) or by (low-pass) whole genome sequencing (WGS). First, ‘GeneBreak’ collects the genomic locations of chromosomal CNA-associated breaks that were previously pinpointed by the segmentation algorithm that was applied to obtain CNA profiles. Next, a tailored annotation approach for breakpoint-to-gene mapping is implemented. Finally, dedicated cohort-based statistics is incorporated with correction for covariates that influence the probability to be a breakpoint gene. In addition, multiple testing correction is integrated to reveal recurrent breakpoint events. This easy-to-use algorithm, ‘GeneBreak’, is implemented in R (www.cran.r-project.org) and is available from Bioconductor (www.bioconductor.org/packages/release/bioc/html/GeneBreak.html).
      PubDate: 2017-07-06T09:24:26Z
      DOI: 10.12688/f1000research.9259.2
      Issue No: Vol. 5 (2017)
       
  • Method-centered digital communities on protocols.io for fast-paced
           scientific innovation [version 2; referees: 2 approved]

    • Authors: Lori Kindler, Alexei Stoliartchouk, Leonid Teytelman, Bonnie L. Hurwitz
      Abstract: The Internet has enabled online social interaction for scientists beyond physical meetings and conferences. Yet despite these innovations in communication, dissemination of methods is often relegated to just academic publishing. Further, these methods remain static, with subsequent advances published elsewhere and unlinked. For communities undergoing fast-paced innovation, researchers need new capabilities to share, obtain feedback, and publish methods at the forefront of scientific development. For example, a renaissance in virology is now underway given the new metagenomic methods to sequence viral DNA directly from an environment. Metagenomics makes it possible to “see” natural viral communities that could not be previously studied through culturing methods. Yet, the knowledge of specialized techniques for the production and analysis of viral metagenomes remains in a subset of labs.  This problem is common to any community using and developing emerging technologies and techniques. We developed new capabilities to create virtual communities in protocols.io, an open access platform, for disseminating protocols and knowledge at the forefront of scientific development. To demonstrate these capabilities, we present a virology community forum called VERVENet. These new features allow virology researchers to share protocols and their annotations and optimizations, connect with the broader virtual community to share knowledge, job postings, conference announcements through a common online forum, and discover the current literature through personalized recommendations to promote discussion of cutting edge research. Virtual communities in protocols.io enhance a researcher’s ability to: discuss and share protocols, connect with fellow community members, and learn about new and innovative research in the field.  The web-based software for developing virtual communities is free to use on protocols.io. Data are available through public APIs at protocols.io.
      PubDate: 2017-06-29T13:40:54Z
      DOI: 10.12688/f1000research.9453.2
      Issue No: Vol. 5 (2017)
       
 
 
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