bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning reduced gene/non-coding RNA features that classify Schizophrenia patients accurately and highlight insightful gene clusters
Authors: Liu Yichuan , Qu Hui-Qi , Chang Xiao , Tian Lifeng , Glessner Joseph , Sleiman Patrick A. M. , Hakonarson Hakon 
Published: June 2020

AbstractSchizophrenia (SCZ) is a chronic and severely disabling neurodevelopmental disorder that affects people worldwide. RNA-seq has been a powerful method to detect the differentially expressed genes/non-coding RNAs in patients; however, due to overfitting problems differentially expressed targets (DETs) cannot be used properly as biomarkers. In this study, dorsolateral prefrontal cortex (dlpfc) RNA-seq data from 254 individuals’ was obtained from the CommonMind consortium and analyzed with machine learning methods, including random forest, forward feature selection (ffs), and factor analysis, to reduce the numbers of gene/non-coding RNA feature vectors to overcome overfitting problem and explore involved functional clusters. In 2-fold shuffle testing, the average predictive accuracy for SCZ patients was 67% based on coding genes, and the 96% based on long non-coding RNAs (lncRNAs). Coding genes were further clustered into 14 factors and lncRNAs were clustered into 45 factors to represent the underlying features. The largest contribution factor for coding genes contains number of genes critical in neurodevelopment and previously reported in relation with various brain disorders. Genomic loci of lncRNAs were more insightful, enriched for genes critical in synapse function (p=7.3E-3), cell junction (p=0.017), neuron differentiation (p=8.3E-3), phosphorylation (8.2E-4), and involving the Wnt signaling pathway (p=0.029). Taken together, machine learning is a powerful algorithm to reduce functional biomarkers in SCZ patients. The lncRNAs capture the characteristics of SCZ tissue more accurately than mRNA as the formers regulate every level of gene expression, not limited to mRNA levels.
FastTrack, A Strategy to Shorten Time to Degree
Authors: Schaller Michael D. , Barbier Mariette 
Published: June 2020

AbstractRecent reports express concern about the sustainability of the biomedical research enterprise in its current form. Recurring concerns include the predictability and sustainability of funding for research, regulatory burden and training the next generation in the biomedical workforce. One specific concern is the duration of training periods during pre-doctoral and post-doctoral studies. This article addresses the issue of time-to-degree (TTD) for doctorates. Many reports stress the importance of shortening the TTD, but provide no recommendations to achieve this goal. Herein, factors potentially affecting TTD are discussed and one mechanism that harmonizes undergraduate and graduate programs is proposed as a strategy to reduce the TTD.
14-3-3 protein Bmh1 triggers short-range compaction of mitotic chromosomes by recruiting sirtuin deacetylase Hst2
Authors: Jain Neha , Janning Petra , Neumann Heinz 
Published: June 2020

AbstractMitotic chromosome compaction is licensed by kinetochores in yeast. Recruitment of Aurora kinase B elicits a cascade of events starting with phosphorylation of H3 S10, which signals the recruitment of lysine deacetylase Hst2 and the removal of H4 K16ac. The unmasked H4 tails interact with the acidic patch of neighbouring nucleosomes to drive short-range compaction of chromatin. Here, we demonstrate that the interaction of Hst2 with H3 S10ph is mediated by 14-3-3 protein Bmh1. As a homodimer, Bmh1 binds simultaneously to H3 S10ph and the phosphorylated C-terminus of Hst2. The Hst2-Bmh1 interaction is cell cycle dependent, reaching its maximum in M phase. Furthermore, we show that phosphorylation of C-terminal residues of Hst2 stimulates its deacetylase activity. Hence, the data presented here identify Bmh1 as a key player in the mechanism of licensing of chromosome compaction in mitosis.Key Points14-3-3 protein Bmh1 bridges the interaction of Hst2 with phosphorylated H3 tailsHst2 is multiply phosphorylated on its unstructured C-terminal tailThe interaction of Bmh1 with Hst2 is cell cycle dependentHst2 phosphorylation enhances its enzymatic activity
Living in the concrete jungle: carnivore spatial ecology in urban parks
Authors: Gámez Siria , Harris Nyeema C. 
Published: June 2020

ABSTRACTPeople and wildlife are living in an increasingly urban world, replete with unprecedented human densities, sprawling built environments, and altered landscapes. Such anthropogenic pressures can affect multiple processes within an ecological community, from spatial patterns to interspecific interactions. We tested two competing hypotheses, human shields versus human competitors, to characterize how humans affect the carnivore community using multi-species occupancy models. From 2017-2020, we conducted the first camera survey of city parks in Detroit, Michigan, and collected spatial occurrence data of the local native carnivore community. Our 12,106-trap night survey captured detected data for coyotes (Canis latrans), red foxes (Vulpes vulpes), gray foxes (Urocyon cinereoargenteus), raccoons (Procyon lotor), and striped skunks (Mephitis mephitis). Overall occupancy varied across species (Ψcoyote=0.40, Ψraccoon=0.54, Ψred fox=0.19, Ψstriped skunk=0.09). Contrary to expectations, humans did not significantly affect individual occupancy for these urban carnivores. However, co-occurrence between coyote and skunk only increased with human activity. The observed positive spatial association between an apex and subordinate pair supports the human shield hypothesis. Our findings demonstrate how urban carnivores can exploit spatial refugia and coexist with humans in the cityscape.
Compensation of physiological motion enables high-yield whole-cell recordingin vivo
Authors: Stoy William M. , Yang Bo , Kight Ali , Wright Nathaniel C. , Borden Peter Y. , Stanley Garrett B. , Forest Craig R. 
Published: June 2020

1.1.1AbstractWhole-cell patch-clamp recordingin vivois the gold-standard method for measuring subthreshold electrophysiology from single cells during behavioural tasks, sensory stimulations, and optogenetic manipulation. However, these recordings require a tight, gigaohm resistance, seal between a glass pipette electrode’s aperture and a cell’s membrane. These seals are difficult to form, especially in vivo, in part because of a strong dependence on the distance between the pipette aperture and cell membrane. We elucidate and utilize this dependency to develop an autonomous method for placement and synchronization of pipette’s tip aperture to the membrane of a nearby, moving neuron, which enables high-yield seal formation and subsequent recordings in the deep in the brain of the living mouse, in the thalamus. This synchronization procedure nearly doubles the reported gigaseal yield in the thalamus (>3 mm below the pial surface) from 26% (n=17/64) to 48% (n=32/66). Whole-cell recording yield improved from 10% (n = 9/88) to 24% (n=18/76) when motion compensation was used during the gigaseal formation. As an example of its application, we utilized this system to investigate the role of the sensory environment and ventral posterior medial region (VPM) projection synchrony on intracellular dynamics in the barrel cortex. This method results in substantially greater subcortical whole-cell recording yield than previously reported and thus makes pan-brain whole-cell electrophysiology practical in the living mouse brain.
Harnessing endogenous repair mechanisms for targeted gene knock-in of bovine embryos
Authors: Owen Joseph R. , Hennig Sadie L. , McNabb Bret R. , Lin Jason C. , Young Amy E. , Murray James D. , Ross Pablo J. , Van Eenennaam Alison L. 
Published: June 2020

ABSTRACTIntroducing useful traits into livestock breeding programs through gene knock-ins has proven challenging. Typically, targeted insertions have been performed in cell lines, followed by somatic cell nuclear transfer cloning, which can be inefficient. An alternative is to introduce genome editing reagents and a homologous recombination (HR) donor template into embryos to trigger homology-directed repair (HDR). However, the HR pathway is primarily restricted to actively dividing cells (S/G2-phase) and its efficiency is low in zygotes, especially for the introduction of large DNA sequences. The homology-mediated end joining (HMEJ)-based strategy harnesses HDR by direct injection of embryos, and has been shown to have an improved knock-in efficiency in non-dividing cells. The knock-in efficiency for a 1.8kb gene was contrasted when combining a gRNA/Cas9 ribonucleoprotein complex with either a traditional HR donor template, or a HMEJ template in bovine zygotes. The HMEJ template resulted in a significantly higher rate of gene knock-in as compared to the HR template (37.0% and 13.8%; P < 0.05). Additionally, more than a third of the knock-in embryos (36.9%) were non-mosaic. This approach will facilitate the one-step introduction of gene constructs at a specific location of the bovine genome and contribute to the next generation of elite cattle.
Pre exposure Hydroxychloroquine Prophylaxis for COVID-19 in healthcare workers: a retrospective cohort
Authors: Bhattacharya Raja , Chowdhury Sampurna , Mukherjee Rishav , Kulshrestha Manish , Ghosh Rohini , Saha Souvik , Nandi Anita 
Published: June 2020

AbstractBackgroundWhile several trials are ongoing for treatment of COVID-19, scientific research on chemoprophylaxis is still lacking even though it has potential to delay the pandemic allowing us time to complete research on vaccines.MethodsWe have conducted a cohort study amongst Health Care Workers (HCW) exposed to COVID-19 patients, at a tertiary care center in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken hydroxychloroquine (HCQ) prior to exposure were considered one cohort while those who had not were considered to be another. All participants with a verifiable contact history were tested for COVID-19 by rtPCR. The two cohorts were comparable in terms of age, gender, comorbidities and exposure. The primary outcome was incidence rates of rtPCR positive COVID-19 infection amongst HCQ users and non users.Results106 healthcare workers were examined in this cohort study of whom 54 were HCQ users and rest were not. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing SARS-CoV-2 infection, compared to those who were not on it, X2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.ConclusionsThis study demonstrated that voluntary HCQ consumption as pre-exposure prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2. These promising findings therefore highlight the need to examine this association in greater detail among a larger sample using Randomised Controlled Trials (RCT).
Quantification of the relative arm-use in patients with hemiparesis using inertial measurement units
Authors: David Ann , ReethaJanetSureka StephenSukumaran , Gayathri Sankaralingam , Annamalai Salai Jeyseelan , Samuelkamleshkumar Selvaraj , Kuruvilla Anju , Magimairaj Henry Prakash , Varadhan SKM , Balasubramanian Sivakumar 
Published: June 2020

AbstractBackgroundThe most popular method for measuring upper limb activity is based on accelerometery. However, this method is prone to overestimation and is agnostic to the functional utility of a movement. In this study, we used an inertial measurement unit(IMU)-based gross movement score to quantify arm-use in hemiparetic patients at home.Objectives(i) Validate the gross movement score detected by wrist-worn IMUs against functional movements identified by human assessors. (ii) Test the feasibility of using wrist-worn IMUs to measure arm-use in patients’ natural settings.MethodsTo validate the gross movement score two independent assessors analyzed and annotated the video recordings of 5 hemiparetic patients and 10 healthy controls performing a set of activities while wearing IMUs. The second study tracked arm-use of 5 hemiparetic patients and 5 healthy controls using two wrist-worn IMUs for 7 days and 3 days, respectively. The IMU data obtained from this study was used to develop quantitative measures (total and relative arm-use (RAU)) and a visualization method for arm-use.ResultsThe gross movement score detects functional movement with 50–60% accuracy in hemiparetic patients, and is robust to non-functional movements. Healthy controls showed a slight bias towards the dominant arm (RAU: 40.52º). Patients’ RAU varied between 15–47º depending upon their impairment level and pre-stroke hand dominance.ConclusionsThe gross movement score performs moderately well in detecting functional movements while rejecting non-functional movements. The patients’ total arm-use is less than healthy controls, and their relative arm-use is skewed towards the less-impaired arm.Clinical trial registry numberCTRI/2018/09/015648
Point of care lung ultrasound is useful when screening for CoVid-19 in Emergency Department patients
Authors: Walsh Paul , Hankins Andrea , Bang Heejung 
Published: June 2020

BackgroundCoVid-19 can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) screening in symptomatic patients with normal vital signs is frequently limited to oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for CoVid-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with CoVid-19 less than 2% of the time.MethodsSubjectsSubjects were identified from ED ultrasound logs.Inclusion criteriaAge 14 years or older with symptoms prompting ED screening for CoVid-19.Exclusion criteriaKnown congestive heart failure or other chronic lung condition likely to cause excessive B lines on LUS.InterventionStructured blinded ultrasound review and chart reviewAnalysisWe used a two-sided exact hypothesis test for binomial random variables. We also measured LUS diagnostic performance using computed tomography as the gold standard.ResultsWe reviewed 77 charts; 49 met inclusion criteria. Vital signs were normal in 30/49 patients; 10 (33%) of these patients had LUS consistent with CoVid-19. We rejected the null hypothesis (p-value < 0.001). The treating physicians’ interpretation of their own point of care lung ultrasounds had a sensitivity of 100% (95% CI 75%, 100%) and specificity of 80% (95% CI 68%, 89%).ConclusionLUS has a meaningful detection rate for CoVid-19 in symptomatic ED patients with normal vital signs. We recommend at least LUS be used in addition to PCR testing when screening symptomatic ED patients for CoVid-19.CapsuleWhat is knownAuscultation and chest x-ray are insufficient to screen for lung involvement when SARS-CoV-2 infection is suspected. Point of care lung ultrasound is widely available, safer, and less resource intensive than CT imaging.What we foundIn symptomatic patients presenting to the ED even those with normal vital signs had point of care lung ultrasound evidence of alveolar level involvement 33%of patients. Point of care lung ultrasound was 100% sensitive and 80% specific compared to CT (reference standard) when evaluating patients for Covid-19.What this addsPoint of care lung ultrasound or similar imaging should performed when screening symptomatic patients in whom SARS-CoV-2 infection is suspected.
Clinical characteristics and factors associated with admission to intensive care units in hospitalized COVID-19 patients in Lyon University Hospitals, France
Authors: Vanhems Philippe , Gustin Marie-Paule , Elias Christelle , Henaff Laetitia , Dananché Cédric , Grisi Beatrice , Marion Elodie , Khanafer Nagham , Hilliquin Delphine , Gardes Sophie , Gerbier-Colomban Solweig , Amour Selilah , Kuczewski Elisabetta , Escuret Vanessa , Lina Bruno , Saadatian-Elahi Mitra 
Published: June 2020

AbstractIntroductionA new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analyzing clinical presentation on admission and the determinants associated with direct admission or transfer to intensive care units (ICUs) in hospitalized COVID-19 patients.Patients and MethodsIn this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients were prospectively collected and analyzed. The outcome was admission/transfer to intensive care units compared with total hospital stay in medical wards according to patient characteristics.ResultsOf the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of admission/transfer to ICUs with male gender (OR, 1.99 [95%CI, 1.07-3.73]), temperature (OR, 1.37 [95% CI, 1.01-1.88] per degree Celsius increase), abnormal lung auscultation on admission (OR, 2.62 [95% CI, 1.40-4.90]), elevated level of CRP (OR, 6.96 [95% CI, 1.45-33.35 for CRP>100mg/L vs CRP<10mg/L). Increased time was observed between symptom onset and hospital admission (OR, 4.82 [95% CI, 1.61-14.43] for time >10 days vs time <3 days) and monocytopenia (OR, 2.49 [95% CI, 1.29-4.82]). Monocytosis was associated with lower risk of admission/transfer to ICUs (OR, 0.25 [95% CI, 0.05-1.13]).ConclusionsClinical and biological features on admission and time until admission were associated with admission to ICUs. Signs to predict worsening on admission could be partially associated with the time until admission. This finding reinforces the need for appropriate guidelines to manage COVID-19 patients in this time window.
Age at Diagnosis Shapes the Prognosis of Childhood Immune Thrombocytopenia
Authors: Schmidt David E. , Edslev Pernille Wendtland , Heitink-Pollé Katja M.J. , Kapur Rick , Porcelijn Leendert , van der Schoot C. Ellen , Vidarsson Gestur , Bruin Marrie C.A. , Rosthøj Steen , de Haas Masja 
Published: June 2020

ABSTRACTObjectiveChildhood immune thrombocytopenia (ITP), an acquired bleeding disorder, occurs at any age. Studies have indicated a less favourable prognosis in children aged above ten years. Low lymphocyte counts have been proposed as predictors of chronic disease. Detailed knowledge of ITP disease characteristics and prognosis at various ages may be useful to support clinical decision-making. We aimed to define how age shapes the clinical characteristics, biological parameters and disease outcomes in childhood ITP.DesignPost-hoc analysis of two prospective European studies (NOPHO ITP study and TIKI trial). Children were followed for 6-12 months.SettingPatient inclusion in paediatrics departments in the Netherlands and the five Nordic countries.PatientsChildren aged <16 years with newly diagnosed ITP (N=577) and severe thrombocytopenia (diagnosis platelet count ≤20 × 109/L).ResultsBy analysing age effects on a continuous scale, we observed that recovery rates at 3-12 months follow-up were gradually reduced in children aged above five years. An absence of a response to IVIg was observed at all ages, but was more common in older children, in particular above 6 years of age. Leukocyte and lymphocyte subset counts were reduced with age, but not elevated or decreased compared to age-appropriate reference intervals. Children aged below seven years showed elevated thrombopoietin levels.ConclusionsAlready from five years of age onwards, there is an increasing risk for a long-lasting course of ITP. Given the varying treatment responses and biological variation, age differences should be considered for the design of clinical trials, prediction models and biological studies.
Assessing the reliability of species distribution projections in climate change research
Authors: Santini Luca , Benítez-López Ana , Maiorano Luigi , Čengić Mirza , Huijbregts Mark A.J. 
Published: June 2020

AbstractAimForecasting changes in species distribution under future scenarios is one of the most prolific areas of application for species distribution models (SDMs). However, no consensus yet exists on the reliability of such models for drawing conclusions on species distribution response to changing climate. In this study we provide an overview of common modelling practices in the field and assess model predictions reliability using a virtual species approach.LocationGlobalMethodsWe first provide an overview of common modelling practices in the field by reviewing the papers published in the last 5 years. Then, we use a virtual species approach and three commonly applied SDM algorithms (GLM, MaxEnt and Random Forest) to assess the estimated (cross-validated) and actual predictive performance of models parameterized with different modelling settings and violations of modelling assumptions.ResultsOur literature review shows that most papers that model species distribution under climate change rely on single models (65%) and small samples (< 50 presence points, 62%), use presence-only data (85%), and binarize models’ output to estimate range shift, contraction or expansion (74%). Our virtual species approach reveals that the estimated predictive performance tends to be over-optimistic compared to the real predictive performance. Further, the binarization of predicted probabilities of presence reduces models’ predictive ability considerably. Sample size is one of the main predictors of real accuracy, but has little influence on estimated accuracy. Finally, the inclusion of irrelevant predictors and the violation of modelling assumptions increases estimated accuracy but decreases real accuracy of model projections, leading to biased estimates of range contraction and expansion.Main conclusionsOur study calls for extreme caution in the application and interpretation of SDMs in the context of biodiversity conservation and climate change research, especially when modelling a large number of species where species-specific model settings become impracticable.
Critical role for astrocyte NAD+glycohydrolase in myelin injury and regeneration
Authors: Langley Monica R. , Choi Chan-Il , Peclat Thais R. , Guo Yong , Simon Whitney , Yoon Hyesook , Kleppe Laurel , Lucchinetti Claudia F. , Chini Claudia C.S. , Chini Eduardo N. , Scarisbrick Isobel A. 
Published: June 2020

AbstractWestern-style diets cause disruptions in myelinating cells and astrocytes within the mouse CNS. CD38 has increased expression in the cuprizone and EAE demyelination models and is the main NAD+depleting enzyme in CNS tissue. Altered NAD+metabolism has been linked to both high fat consumption and Multiple Sclerosis (MS). We identified increased CD38 expression in the male mouse spinal cord following chronic high fat consumption or focal lysolecithin-induced demyelinating injury as well as in reactive astrocytes within an active MS lesion. CD38-catalytically inactive mice are significantly protected from high fat-induced NAD+depletion, oligodendrocyte loss, oxidative damage, and astrogliosis. 78c, a CD38 inhibitor, increased NAD+and attenuated neuroinflammatory changes in astrocytes induced by saturated fat. Conditioned media from saturated fat-treated astrocytes impaired oligodendrocyte differentiation pointing to indirect mechanisms of oligodendrogliopathy. Combined saturated fat and lysolecithin demyelination in cerebellar slices resulted in additional deficits in myelin proteins that were mitigated by concomitant 78c treatment. Importantly, oral 78c increased counts of oligodendrocytes and remyelinated axons after focal demyelination. Our findings suggest high fat diet impairs oligodendrocyte survival and differentiation through astrocyte-linked mechanisms mediated by the NAD+ase CD38, and highlight the use of CD38 inhibitors as potential therapeutic candidates to improve myelin regeneration.