bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19)
Authors: Diao Bo , Wang Chenhui , Tan Yingjun , Chen Xiewan , Liu Ying , Ning Lifen , Chen Li , Li Min , Liu Yueping , Wang Gang , Yuan Zilin , Feng Zeqing , Wu Yuzhang , Chen Yongwen 
Published: February 2020

SummaryBACKGROUNDThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear.METHODSWe retrospectively reviewed the counts of total T cells, CD4+, CD8+T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases.RESULTSThe number of total T cells, CD4+and CD8+T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (⩾60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/μL, 300/μL, or 400/μL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-α concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-α concentrations and restored T cell counts. Finally, T cells from COVID-19 patients have significantly higher levels of the exhausted marker PD-1 as compared to health controls. Moreover, increasing PD-1 and Tim-3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion.CONCLUSIONST cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/μL, 300/μL, and 400/μL, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
Psychological responses, behavioral changes and public perceptions during the early phase of the COVID-19 outbreak in China: a population based cross-sectional survey
Authors: Qian Mengcen , Wu Qianhui , Wu Peng , Hou Zhiyuan , Liang Yuxia , Cowling Benjamin J. , Yu Hongjie 
Published: February 2020

AbstractObjectiveTo investigate psychological and behavioral responses to the threat of SARS-CoV-2 infections and their associations with public perceptions in ChinaDesignCross sectional population-based telephone survey via random digital dialing between 1 and 10 February, 2020SettingWuhan (the epicentre and quarantined city), and Shanghai (a typical major city with close transportation link with Wuhan)ParticipantsRandom sample of 510 residents in Wuhan and 501 residents in Shanghai aged above 18Main outcome measuresAnxiety (measured by the 7-item generalized anxiety disorder [GAD-7] scale), recommended and avoidance behaviors (engaged in all six behaviors such as increasing surface cleaning and reducing going out).ResultsThe prevalence rates of moderate or severe anxiety (score ≥10 on GAD-7) were 32.7% (n=167) among Wuhan participants and 20.4% (n=102) among Shanghai participants. 78.6% (n=401) of Wuhan participants and 63.9% (n=320) of Shanghai participants had carried out all six precautionary behaviors. For both measures, Wuhan participants were more responsive to the outbreak (p<0.001). Controlling for personal characteristics, logistic regression results suggested that risks of moderate or severe anxiety were positively associated with perceived susceptibility (odds ratio 1.6, 95% confidence interval 1.3-1.8) and severity of the disease (1.6, 1.4-1.9) and confusion about information reliability (1.6, 1.5-1.9). Having confidence in taking measures to protect oneself against the disease was associated with a lower risk (0.6, 0.5-0.7). The strongest predictor of behavioral change was perceived severity (1.2, 1.1-1.4), followed by confusion about information reliability (1.1, 1.0-1.3).ConclusionsPsychological and behavioral responses to COVID-19 have been dramatic during the rising phase of the outbreak. Our results support efforts for timely dissemination of accurate and reliable information to address the high anxiety level.
Geometric Semi-automatic Analysis of Colles’ Fractures
Authors: Reyes-Aldasoro Constantino Carlos , Ngan Kwun Ho , Ananda Ananda , Garcez Artur d’Avila , Appelboam Andy , Knapp Karen M. 
Published: February 2020

AbstractFractures of the wrist are common in Emergency Departments, where some patients are treated with a procedure called Manipulation under Anaesthesia. In some cases this procedure is unsuccessful and patients need to visit the hospital again where they undergo surgery to treat the fracture. This work describes a geometric semi-automatic image analysis algorithm to analyse and compare the x-rays of healthy controls and patients with dorsally displaced wrist fractures (Colles’ fractures) who were treated with Manipulation under Anaesthesia. A series of 161 posterior-anterior radiographs from healthy controls and patients with Colles’ fractures were acquired and analysed. The patients’ group was further subdivided according to the outcome of the procedure (successful/unsuccessful) and pre- or post-intervention creating five groups in total (healthy, pre-successful, pre-unsuccessful, post-successful, post-unsuccessful). The semi-automatic analysis consisted of manual location of three landmarks (finger, lunate and radial styloid) and automatic processing to generate 32 geometric and texture measurements, which may be related to conditions such as osteoporosis and swelling of the wrist. Statistical differences were found between patients and controls and pre- and post-intervention, but not between the procedures. The most distinct measurements were those of texture. Although the study includes a relatively low number of cases and measurements, the statistical differences are encouraging.
Modeling and Prediction of the 2019 Coronavirus Disease Spreading in China Incorporating Human Migration Data
Authors: Zhan Choujun , Tse Chi K. , Fu Yuxia , Lai Zhikang , Zhang Haijun 
Published: February 2020

AbstractThis study integrates the daily intercity migration data with the classic Susceptible-Exposed-Infected-Removed (SEIR) model to construct a new model suitable for describing the dynamics of epidemic spreading of Coronavirus Disease 2019 (COVID-19) in China. Daily intercity migration data for 367 cities in China are collected from Baidu Migration, a mobile-app based human migration tracking data system. Historical data of infected, recovered and death cases from official source are used for model fitting. The set of model parameters obtained from best data fitting using a constrained nonlinear optimization procedure is used for estimation of the dynamics of epidemic spreading in the coming weeks. Our results show that the number of infections in most cities in China will peak between mid February to early March 2020, with about 0.8%, less than 0.1% and less than 0.01% of the population eventually infected in Wuhan, Hubei Province and the rest of China, respectively.
Views about integrating smoking cessation treatment within psychological services for patients with common mental illness: a multi-perspective qualitative study
Authors: Taylor Gemma , Sawyer Katherine , Kessler David , Munafò Marcus , Aveyard Paul , Shaw Alison 
Published: February 2020

ABSTRACTBackgroundSmoking rates are significantly higher in people with mental health problems, compared to those without. Negative attitudes towards smoking cessation are widespread in inpatient settings towards patients with severe and enduring mental illness. It is not clear if the same attitudes operate in psychological services towards people with common mental illness. We aimed to understand the concerns and views that patients, therapists, and smoking cessation practitioners may have about integrating smoking cessation treatment into psychological treatment for common mental illness and how these concerns may be overcome.MethodsThematic analysis of 23 in-depth interviews. Interviews took place in Improving Access to Psychological Therapies (IAPT) and smoking cessation services in England. Participants were 11 psychological wellbeing practitioners (PWPs), six IAPT patients with common mental illness, and six smoking cessation advisors.OutcomesNone.FindingsIAPT patients reported psychological benefits from smoking, but also described smoking as a form of therapeutic self-harm. PWPs seem positive towards smoking cessation treatment for people with common mental illness. IAPT PWPs and patients accept evidence that smoking tobacco may harm mental health, and quitting might benefit mental health. PWPs report expertise in helping people with common mental illness to make behavioural changes in the face of mood disturbances and poor motivation. IAPT appears to be a natural environment for smoking cessation intervention. PWPs felt confident to offer smoking cessation treatments to IAPT patients, but thought that a reduction in caseload was required to deliver smoking cessation support in an already pressed service.
Association of Population migration and Coronavirus Disease 2019 epidemic control
Authors: Ding Yu , Luo Sihui , Zheng Xueying , Ling Ping , Yue Tong , Liu Zhirong , Weng Jianping 
Published: February 2020

AbstractBackground and ObjectiveTo analyze the impact of different patterns of migration flow in two cities, Hefei and Shenzhen, on the epidemic and disease control of Coronavirus Disease 2019 (COVID-19), in order to provide insight for making differentiated controlling policies.MethodsWe collected demographic and epidemiological information of confirmed COVID-19 cases in Hefei and Shenzhen between January 19 and February 11, 2020, from data officially published by the provincial and municipal Centers for Disease Control and Prevention (CDC). From these data we calculated basic reproduction number R0 to reflect the rate of spread of COVID-19 in these cities. Aggregated data of population migration during the same period was extracted from Baidu Migration. The change of R0 in the two cites were analyzed and compared. Spearman correlation analysis between R0 and population inflow from epidemic focus were performed.ResultsA total of 157 confirmed cases was identified in Hefei by 24:00 February 11, 2020, with an average age of 44.4±15.6 years, 74 female (47.1%) and 386 confirmed cases were identified in Shenzhen, with an average age of 45.15±17.99 years, 202 female (52.3%). Significant difference in the proportion of imported cases between the two cities was observed (Hefei vs Shenzhen, 24.2% vs 74.9%, p=0.000). Before January 31 2020, during the initial stage of the Level 1 Response to Major Public Health Emergencies, there was no significant association observed in Shenzhen between R0 and the proportion of population inflow from the epidemic focus (P =0.260, r=-0.452); meanwhile in Hefei, such association was strong (P =0.000, r=1.0). However, after the initial stage of response, the situation reversed. A weak association was observed in Shenzhen between be R0 and the proportion of population inflow from the epidemic focus (P=0.073, r=0.536) but not in Hefei (P =0.498, r=0.217).ConclusionFollowing Level 1 Response, consistent decline of R0 of COVID-19 was observed in both Hefei and Shenzhen. Different patterns of disease spread were observed in the two cities, driven by different patterns of population migration. This indicated that population migration should be taken into consideration when we set controlling policy of a novel infectious disease.
Fly wing evolution explained by a neutral model with mutational pleiotropy
Authors: Jiang Daohan , Zhang Jianzhi 
Published: February 2020

ABSTRACTTo what extent the speed of mutational production of phenotypic variation determines the rate of long-term phenotypic evolution is a central question in evolutionary biology. In a recent study, Houleet al.addressed this question by studying the mutational variation, microevolution, and macroevolution of locations of vein intersections on fly wings, reporting very slow phenotypic evolution relative to the rates of mutational input, high phylogenetic signals of these traits, and a strong, linear correlation between the mutational variance of a trait and its rate of evolution. Houleet al. examined multiple models of phenotypic evolution but found none consistent with all these observations. Here we demonstrate that the purported linear correlation between mutational variance and evolutionary divergence is an artifact. More importantly, patterns of fly wing evolution are explainable by a simple model in which the wing traits are neutral or neutral within a range of phenotypic values but their evolutionary rates are reduced because most mutations affecting these traits are purged owing to their pleiotropic effects on other traits that are under stabilizing selection. We conclude that the evolutionary patterns of fly wing morphologies are explainable under the existing theoretical framework of phenotypic evolution.
Efficient coding of numbers explains decision bias and noise
Authors: Prat-Carrabin Arthur , Woodford Michael 
Published: February 2020

AbstractHuman subjects differentially weight different stimuli in averaging tasks, which has been interpreted as reflecting encoding bias. We examine the alternative hypothesis that stimuli are encoded with noise, then optimally decoded. Under a model of efficient coding, the amount of noise should vary across stimuli, and depend on statistics of the stimuli. We investigate these predictions through a task in which participants are asked to compare the averages of two series of numbers, each sampled from a prior distribution that varies across blocks of trials. Subjects encode numbers with a bias and a noise that both depend on the number. Infrequently occurring numbers are encoded with more noise. We show how an efficient-coding, Bayesian-decoding model accounts for these patterns, and best captures subjects’ behaviour. Finally, our results suggest that Wei and Stocker’s “law of human perception”, which relates the bias and variability of sensory estimates, also applies to number cognition.
Vitamin D receptor protects against dysbiosis and tumorigenesis via the JAK/STAT pathway in intestine
Authors: Zhang Yong-Guo , Lu Rong , Wu Shaoping , Chatterjee Ishita , Zhou David , Xia Yinglin , Sun Jun 
Published: February 2020

AbstractBackgroundVitamin D exerts regulatory roles via vitamin D receptor (VDR) in mucosal immunity, host defense, and inflammation involving host factors and microbiome. HumanVdrgene variation shapes the microbiome and VDR deletion leads to dysbiosis. Low VDR expression and diminished vitamin D/VDR signaling are observed in colon cancer. Nevertheless, how intestinal epithelial VDR is involved in tumorigenesis through gut microbiota remains unknown. We hypothesized that intestinal VDR protects mice against dysbiosis via modulating the JAK/STAT pathway in tumorigenesis. To test our hypothesis, we used an azoxymethane/Dextran Sulfate Sodium-induced cancer model in intestinal VDR conditional knockout (VDRΔIEC) mice, cell cultures, stem-cell derived colonoids, and human colon cancer samples.ResultsVDRΔIECmice have higher numbers of tumors with location shifted from distal to proximal colon. Fecal microbiota analysis showed that VDR deletion leads to bacterial profile shift from normal to susceptible carcinogenesis. We found enhanced bacterial staining in mouse and human tumors. Microbial metabolites from VDRΔIECmice showed elevated secondary bile acids, consistent with the observations in human CRC. We further identified that VDR protein bound to the Jak2 promoter, suggesting that VDR transcriptionally regulated Jak2. The JAK/STAT pathway is critical in intestinal and microbial homeostasis. Fecal samples from VDRΔIECmice activate the STAT3 activation in human and mouse organoids. Lack of VDR led to hyperfunction of Jak2 in respond to intestinal dysbiosis. A JAK/STAT inhibitor abolished the microbiome-induced activation of STAT3.ConclusionWe provide insights into the mechanism of VDR dysfunction leading to dysbiosis and tumorigenesis. It indicates a new target — microbiome and VDR for prevention of cancer.
A generalizable method for false-discovery rate estimation in mass spectrometry-based lipidomics
Authors: Fujimoto Grant M. , Kyle Jennifer E. , Lee Joon-Yong , Metz Thomas O. , Payne Samuel H. 
Published: February 2020

AbstractMass spectrometry (MS)-based lipidomics is revolutionizing lipid research with high throughput identification and quantification of hundreds to thousands of lipids with the goal of elucidating lipid metabolism and function. Estimates of statistical confidence in lipid identification are essential for downstream data interpretation in a biological context. In the related field of proteomics, a variety of methods for estimating false-discovery are available, and understanding the statistical confidence of identifications is typically required for data analysis and hypothesis testing. However, there is no current method for estimating the false discovery rate (FDR) or statistical confidence for MS-based lipid identifications. This has slowed the adoption of MS-based lipidomics research, as all identifications require manual inspection and validation to ensure their accuracy. We present here the first generalizable method for FDR estimation, a target/decoy approach, that allows those conducting MS-based lipidomics research to confidently adjust spectral score thresholds to minimize false discovery and to enable full automation of data analysis.
Influence of Energy Deficiency on the Molecular Processes ofSubstantia Nigra Pars CompactaCell for Understanding Parkinsonian Neurodegeneration: A Comprehensive Biophysical Computational Model
Authors: Muddapu Vignayanandam R. , Chakravarthy V. Srinivasa 
Published: February 2020

ABSTRACTParkinson’s disease (PD) is the second most prominent neurodegenerative disease around the world. Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss is not clearly elucidated. We hypothesize that “Energy deficiency at a sub-cellular/cellular/systems level can be a common underlying cause for SNc cell loss in PD.” Here, we propose a comprehensive computational model of SNc cell which helps us to understand the pathophysiology of neurodegeneration at subcellular level in PD. The proposed model incorporates a rich vein of molecular dynamics related to SNc neurons such as ion channels, active pumps, ion exchangers, dopamine turnover processes, energy metabolism pathways, calcium buffering mechanisms, alpha-synuclein aggregation, Lewy body formation, reactive oxygen species (ROS) production, levodopa uptake, and apoptotic pathways. The proposed model was developed and calibrated based on experimental data. The influx of glucose and oxygen into the model was controlled, and the consequential ATP variations were observed. Apart from this, the dynamics of other molecular players (alpha-synuclein, ROS, calcium, and dopamine) known to play an important role in PD pathogenesis are also studied. The aim of the study was to see how deficits in supply of energy substrates (glucose and oxygen) lead to a deficit in ATP, and furthermore, deficits in ATP are the common factor underlying the pathological molecular-level changes including alpha-synuclein aggregation, ROS formation, calcium elevation, and dopamine dysfunction. The model suggests that hypoglycemia plays a more crucial role in leading to ATP deficits than hypoxia. We believe that the proposed model provides an integrated modelling framework to understand the neurodegenerative processes underlying PD.
Frequency of mispackaging ofProchlorococcusDNA by cyanophage
Authors: Laurenceau Raphaël , Raho Nicolas , Forget Mathieu , Arellano Aldo , Chisholm Sallie W. 
Published: February 2020

ABSTRACTProchlorococcuscells are the numerically dominant phototrophs in the open ocean. Cyanophages that infect them are thus a notable fraction of the total viral population in the euphotic zone, and, as vehicles of horizontal gene transfer, appear to drive their evolution. Here we examine the propensity of three cyanophages – a podovirus, a siphovirus, and a myovirus – to mispackage host DNA in their capsids while infectingProchlorococcus,the first step in phage-mediated horizontal gene transfer. We find the mispackaging frequencies are distinctly different among the three phages. Myoviruses mispackage host DNA at low and stable frequencies, while podo- and siphoviruses vary in their mispackaging frequencies by orders of magnitude depending on growth light intensity. We attribute this difference to the concentration of intracellular reactive oxygen species and protein synthesis rates. Based on our findings, we propose a model of mispackaging frequency determined by the imbalance between the production of capsids and the number of phage genome copies during infection.
Diastolic Dysfunction Accompanies Alterations in Myocardial Structure, Cellular Composition and Macrophage Polarization in Survivors of Ionizing Radiation Exposure
Authors: Michalson Kristofer T. , Dugan Gregory O. , Caudell David L. , Cline J. Mark , Kitzman Dalane W. , Register Thomas C. 
Published: February 2020

ABSTRACTRationaleRadiation induced heart disease (RIHD) is a significant delayed/late effect of ionizing radiation exposure.ObjectiveTo determine the cardiac effects of total body irradiation (TBI) in male rhesus macaques, a translational non-human primate (NHP) model.Methods and ResultsEchocardiography was performed on survivors of a single dose (6.4-8.5 Gy) of TBI (n=34) and non-irradiated controls (n=26) divided into longer (LT IRR) and shorter term (ST IRR) survivors and controls to assess the effects of time since TBI on phenotypes. LT IRR had increased Doppler transmitral early filling velocities (E), decreased early mitral annular descent velocities (e’), and higher E/e’ ratio compared to LT CTL (all p≤0.05), indicating left ventricular (LV) diastolic dysfunction. Echocardiographic stroke volume, cardiac output, and end-diastolic and systolic volumes were also lower in LT IRR than controls (all p ≤ 0.05). ST IRR had similar alterations in LV diastolic function but not in cardiac volumetric measures. Analyses of LV, interventricular septum (IVS), and right ventricle (RV) myocardium from deceased irradiated animals (n=17) exposed to a single dose (6.9-8.05 Gy) TBI and non-irradiated controls (n=12) showed that IRR animals had decreased LV and IVS capillary density, and increased LV fibrosis, pan-cardiac fibroblast and macrophage staining, LV and IVS M2 macrophages, and pan-cardiac M1 macrophages (all p<0.05). While M2 predominated over M1 macrophages in both groups, M1 showed greater increases than M2 in IRR.ConclusionsLV diastolic dysfunction due to radiation exposure may be due to a combination of capillary rarefication, activation and expansion of fibroblasts, and increased accumulation of both pro-fibrotic and pro-inflammatory macrophages, all of which lead to increased myocardial stiffness due to fibrosis. Collectively, these findings provide insights into the delayed effects of acute ionizing radiation exposure and suggest that therapies targeting macrophage regulation of fibrosis may mitigate radiation induced heart disease.