bluuebunny/crossref_metadata_2025_split huggingface dataset:
The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, Hubei, China
Authors: Gao Qijun , Hu Yingfu , Dai Zhiguo , Xiao Feng , Wang Jing , Wu Jing 
Published: March 2020

AbstractBackgroundThere is currently a global outbreak of coronavirus disease 2019 (COVID-19),and its epidemic characteristics in the areas where the outbreak has been successfully controlled are rarely reported.ObjectiveDescribe the epidemic characteristics of COVID-19 in Jingmen,Hubei,introduce the local prevention and control experience,and observe the impact of various prevention and control measures on the number of new cases.MethodsAll the COVID-19 patients diagnosed in the municipal districts of Jingmen from January 12 to February 29,2020 were enrolled in this study. We described epidemiological data and observed the impact of control measures on the epidemic.FindingsOf the 219 cases (110 men and 109 women), 88 (40%) had exposure to Wuhan. The median age was 48 years (range,2-88 years;IQR,35-60). Thirty-three severe patients with a median age of 66 years(range,33-82 years,IQR,57-76) were treated in intensive care units; out of these patients, 66.7 %(22) were men and 19 (57.5%) had chronic diseases, including hypertension, diabetes, heart failure, stroke, and renal insufficiency. Under the control measures, the number of new patients gradually decreased and nearly disappeared after 18 days. Wearing masks in all kinds of situations prevents most infections and is one of the most effective prevention and control measures.InterpretationIn conclusion,all people are susceptible to COVID-19, and older males and those with comorbid conditions are more likely to become severe cases. Even though COVID-19 is highly contagious,control measures have proven to be very effective, particularly wearing masks,which could prevent most infections.FundingSupported by the Major Program of Technological Innovation of Hubei Province.
Clinical Characteristics of SARS-CoV-2 Pneumonia Compared to Controls in Chinese Han Population
Authors: Xu Yang , Li Yi-rong , Zeng Qiang , Lu Zhi-bing , Li Yong-zhe , Wu Wei , Dong Sheng-yong , Huang Gang , Wang Xing-huan 
Published: March 2020

AbstractBackgroundIn December 2019, novel coronavirus (SARS-CoV-2) infected pneumonia occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in Chinese Han population is limited. Our objective is to describe the epidemiological and clinical characteristics of SARS-CoV-2 pneumonia without comorbidities compared to normal controls in the Chinese Han population.MethodsRetrospective, multi-center case series of the 69 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia, from February 7 to February 28, 2020; final date of follow-up was February 29, 2020.ResultsThe study population included 69 hospitalized patients with confirmed SARS-CoV-2 pneumonia without comorbidities and 14,117 normal controls. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. Compared with mild patients (n=44), severe or critical patients (n=25) were significantly older (median age, 67 years [IQR, 58-79] vs. 49 years [IQR, 36-60]; p<0.01). Fever was present in 98.6% of the patients. The second most common symptom was cough (62.3%), fatigue (58.0%), sputum (39.1%), and headache (33.3%). The median incubation period was 4 days (IQR, 2 to 7). Leukocyte count was 74.1% of normal controls and lymphocyte count was 45.9% of normal controls. The phenomenon of lymphocyte depletion (PLD) observed in severe or critical cases in 100%. Levels of lactate dehydrogenase, D-dimer, procalcitonin, and interleukin-6 were showed significant differences between mild and severe or critical cases. Chest computed tomographic scans showed bilateral patchy patterns (49.3%), local patchy shadowing (29.0%), and ground glass opacity (21.7%). 7.3% patients were diagnosed ARDS, 7.3% patients were diagnosed acute cardiac injury (troponin I >28 pg/mL) and 4.4% patients were diagnosed fungal infections or shock. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery.ConclusionsIn this multicenter case series of 69 patients without comorbidities, the full spectrum of asymptomatic, mild, severe, and critical cases is described. 50.7% patients were male and 49.3% were female; 1.5% patients were asymptomatic cases, 63.8% patients were mild cases, and 36.2% patients were severe or critical cases. 4.3% patients have been discharged; 1.5% patient had died; 1.5% patient had recovery. Among the 25 patients with severe or critical disease, 12.0% patients were underwent non-invasive mechanical ventilation, 8.0% patients underwent invasive mechanical ventilation, and 4.0% patients died.
Smartphone-Based Symbol-Digit Modalities Test Reliably Measures Cognitive Function in Multiple Sclerosis Patients
Authors: Pham Linh , Harris Thomas , Varosanec Mihael , Kosa Peter , Bielekova Bibiana 
Published: March 2020

AbstractLimited time for patient encounters prevents reliable evaluation of all neurological functions in routine clinical practice. Quantifying neurological disability in a patient-autonomous manner via smartphones may remedy this problem, if such tests provide reliable, disease-relevant information.We developed a smartphone version of the cognitive processing speed test, the Symbol-Digit Modalities Test (SDMT), and assessed its clinical utility. The traditional SDMT uses identical symbol-number codes, allowing memorization after repeated trials. In the phone app, the symbol-number codes are randomly generated.In 154 multiple sclerosis (MS) patients and 39 healthy volunteers (HV), traditional and smartphone SDMT have good agreement (Lin’s coefficient of concordance [CCC] = 0.84) and comparable test-retest variance. In subjects with available volumetric MRI and digitalized neurological examinations (112 MS, 12 HV), the SDMT scores were highly associated with T2 lesion load and brain parenchymal fraction, when controlled for relevant clinical characteristics. The smartphone SDMT association with clinical/imaging features was stronger (R2 = 0.75, p < 0.0001) than traditional SDMT (R2 = 0.65, p < 0.0001). In the longitudinal subcohort, improvements from testing repetition (learning effects), were identifiable using non-linear regression in 14/16 subjects and, on average, peaked after 8 trials. Averaging several post-learning SDMT results significantly lowers the threshold for detecting true decline in test performance.In conclusion, smartphone, self-administered SDMT is a reliable substitute of the traditional SDMT for measuring processing speed in MS patients. Granular measurements at home increase sensitivity to detect true performance decline in comparison to sporadic assessments in the clinic.
Ancient and modern genomes reveal microsatellites maintain a dynamic equilibrium through deep time
Authors: McComish Bennet J. , Charleston Michael A. , Parks Matthew , Baroni Carlo , Salvatore Maria Cristina , Li Ruiqiang , Zhang Guojie , Millar Craig D. , Holland Barbara R. , Lambert David M. 
Published: March 2020

AbstractMicrosatellites are widely used in population genetics, but their evolutionary dynamics remain poorly understood. It is unclear whether microsatellite loci drift in length over time. We identify more than 27 million microsatellites using a novel and unique dataset of modern and ancient Adélie penguin genomes along with data from 63 published chordate genomes. We investigate microsatellite evolutionary dynamics over two time scales: one based on the Adélie penguin samples dating to approximately 46.5 kya, the other dating to the diversification of chordates more than 500 Mya. We show that the process of microsatellite allele length evolution is at dynamic equilibrium; while there is length polymorphism among individuals, the length distribution for a given locus remains stable. Many microsatellites persist over very long time scales, particularly in exons and regulatory sequence. These often retain length variability, suggesting that they may play a role in the maintenance of evolutionary plasticity.
Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration
Authors: Bolado-Carrancio Alfonso , Rukhlenko Oleksii S. , Nikonova Elena , Tsyganov Mikhail A. , Wheeler Anne , Munoz Amaya Garcia , Kolch Walter , von Kriegsheim Alex , Kholodenko Boris N. 
Published: March 2020

AbstractMigrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells.
Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33
Authors: Schumacher Michael A. , Hsieh Jonathan J. , Liu Cambrian Y. , Appel Keren L. , Waddell Amanda , Almohazey Dana , Katada Kay , Bernard Jessica K. , Bucar Edie B. , Gadeock Safina , Maselli Kathryn M. , Washington M. Kay , Grikscheit Tracy C. , Warburton David , Rosen Michael J. , Frey Mark R. 
Published: March 2020

AbstractDynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we asked whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion led to expanded goblet and tuft cell populations. Sprouty2 loss induced PI3K/Akt signaling, leading to GSK3β inhibition and epithelial interleukin (IL)-33 expression. In vivo, this resulted in increased stromal IL-13+ cells. IL-13 in turn induced tuft and goblet cell expansion in vitro and in vivo. Sprouty2 was downregulated by inflammation; this appeared to be a protective response, as VillinCre;Sprouty2F/Fmice were resistant to DSS colitis. In contrast, Sprouty2 was elevated in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.
Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Endosomal Sensing by Dendritic Cells in Psoriasis
Authors: Lou Fangzhou , Sun Yang , Xu Zhenyao , Niu Liman , Wang Zhikai , Deng Siyu , Liu Zhaoyuan , Zhou Hong , Bai Jing , Yin Qianqian , Cai Xiaojie , Sun Libo , Wang Hong , Wu Zhouwei , Chen Xiang , Shi Yuling , Tao Wufan , Ginhoux Florent , Wang Honglin 
Published: March 2020

SUMMARYThe mechanisms underlying tissue-specific chronic inflammation are elusive. Here we report that mice lacking Protein Phosphatase 6 in keratinocytes are predisposed to psoriasis-like skin inflammation, with an inordinate urea cycle and enhanced oxidative phosphorylation that supports hyperproliferation. This phenotype is mediated by increased Arginase-1 production resulting from CCAAT/enhancer-binding protein beta activation. Single-cell RNA-seq of the psoriatic epidermis revealed that the rate-limiting enzyme for Arginine biosynthesis, Argininosuccinate synthetase 1, maintains the Arginine pool, which is indispensable for immune responses. Accumulated polyamines branched from the urea cycle promote endosomal Tlr7-dependent self-RNA sensing by myeloid dendritic cells. This process is achieved with the assistance of an RNA-binding peptide that originates from the heterogeneous nuclear ribonucleoprotein A1, a probable autoantigen in psoriasis. Finally, targeting urea cycle wiring with an arginase inhibitor markedly improved skin inflammation in murine and non-human primate models of psoriasis. Our findings suggest that urea cycle alteration and excessive polyamine production by psoriatic keratinocytes promote self-RNA sensing by dendritic cells, which links the hyperproliferation of stationary cells with innate-immune activation in an auto-inflammatory condition.
Nonalcoholic fatty liver disease is associated with decreased hepatocyte mitochondrial respiration, but not mitochondrial number
Authors: Sinton MC , Ripolles J Meseguer , Villarin B Lucendo , Lyall MJ , Carter RN , Morton NM , Hay DC , Drake AJ 
Published: March 2020

AbstractNonalcoholic fatty liver disease (NAFLD) is currently the most prevalent form of liver disease worldwide. This term covers a spectrum of pathologies, from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH). As the disease progresses, NASH can develop into cirrhosis and hepatocellular carcinoma. However, the underlying mechanisms and the factors which predispose an individual to disease progression remain poorly understood. Whilst NAFLD appears to be associated with mitochondrial dysfunction, it is unclear whether this is due to respiratory impairment, changes in mitochondrial mass, or mitochondrial fragmentation. Using a human pluripotent stem cell-based model of NAFLD we show that exposure to lactate, pyruvate and octanoic acid results in the development of macrovesicular steatosis. We do not observe changes in mitochondrial mass or fragmentation but do find decreases in maximal respiration and reserve capacity, suggesting impairment in the electron transport chain (ETC). Taken together, these findings indicate that the development of macrovesicular steatosis in NAFLD may be linked to the impairment of the ETC in mitochondria.
MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas
Authors: Oldrini Barbara , Vaquero-Siguero Nuria , Mu Quanhua , Kroon Paula , Zhang Ying , Galán-Ganga Marcos , Bao Zhaoshi , Wang Zheng , Liu Hanjie , Sa Jason K , Zhao Junfei , Kim Hoon , Rodriguez-Perales Sandra , Nam Do-Hyun , Verhaak Roel GW , Rabadan Raul , Jiang Tao , Wang Jiguang , Squatrito Massimo 
Published: March 2020

AbstractTemozolomide (TMZ) is an oral alkylating agent used for the treatment of glioblastoma and is now becoming a chemotherapeutic option in patients diagnosed with high-risk low-grade gliomas. The O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the direct repair of the main TMZ-induced toxic DNA adduct, the O6-Methylguanine lesion.MGMTpromoter hypermethylation is currently the only known biomarker for TMZ response in glioblastoma patients. Here we show that a subset of recurrent gliomas carriesMGMTgenomic rearrangements that lead to MGMT overexpression, independently from changes in its promoter methylation. By leveraging the CRISPR/Cas9 technology we generated some of theseMGMTrearrangements in glioma cells and demonstrated that theMGMTgenomic rearrangements contribute to TMZ resistance bothin vitroandin vivo. Lastly, we showed that such fusions can be detected in tumor-derived exosomes and could potentially represent an early detection marker of tumor recurrence in a subset of patients treated with TMZ.
Disease Risk Analysis in sea turtles: A baseline study to inform conservation efforts
Authors: Mashkour Narges , Jones Karina , Hipolito Teresa Valerio , Kophamel Sara , Ahasan Shamim , Walker Grant , Jakob-Hoff Richard , Whittaker Maxine , Hamann Mark , Bell Ian , Elliman Jennifer , Owens Leigh , Saladin Claire , Crespo-Picazo Jose Luis , Gardner Brett , Loganathan Aswini Leela , Bowater Rachel , Young Erina , Barnes Andrew , Robinson David , Baverstock Warren , Blyde David , March Duan , Eghbali Maryam , Mohammadi Maryam , Freggi Daniela , Giliam Jane , Hale Mike , Nicolle Nicholas , Spiby Kevin , Wrobel Daphne , Parga Mariluz , Mobaraki Asghar , Rajakaruna Rupika , Hyland Kevin P. , Read Mark , Ariel Ellen 
Published: March 2020

AbstractThe impact of a range of different threats has resulted in the listing of six out of seven sea turtle species on the IUCN Red List of endangered species. Disease risk analysis (DRA) tools are designed to provide objective, repeatable and documented assessment of the disease risks for a population and measures to reduce these risks through management options. To the best of our knowledge, DRAs have not previously been published for sea turtles, although disease is reported to contribute to sea turtle population decline. Here, a comprehensive list of health hazards is provided for all seven species of sea turtles. The possible risk these hazards pose to the health of sea turtles were assessed and “One Health” aspects of interacting with sea turtles were also investigated. The risk assessment was undertaken in collaboration with more than 30 experts in the field including veterinarians, microbiologists, social scientists, epidemiologists and stakeholders, in the form of two international workshops and one local workshop. The general finding of the DRA was the distinct lack of knowledge regarding a link between the presence of pathogens and diseases manifestation in sea turtles. A higher rate of disease in immunocompromised individuals was repeatedly reported and a possible link between immunosuppression and environmental contaminants as a result of anthropogenic influences was suggested. Society based conservation initiatives and as a result the cultural and social aspect of interacting with sea turtles appeared to need more attention and research. A risk management workshop was carried out to acquire the insights of local policy makers about management options for the risks relevant to Queensland and the options were evaluated considering their feasibility and effectiveness. The sea turtle DRA presented here, is a structured guide for future risk assessments to be used in specific scenarios such as translocation and head-starting programs.
Long-read sequencing to interrogate strain-level variation among adherent-invasiveEscherichia coliisolated from human intestinal tissue
Authors: Wang Jeremy , Bleich Rachel , Zarmer Sandra , Zhang Shiying , Dogan Belgin , Simpson Kenneth W , Arthur Janelle 
Published: March 2020

AbstractAdherent-invasiveEscherichia coli(AIEC) is a pathovar linked to inflammatory bowel diseases (IBD), especially Crohn’s disease, and colorectal cancer. AIEC are genetically diverse, and in the absence of a universal molecular signature, are defined byin vitrofunctional attributes. The relative ability of difference AIEC strains to colonize, persist, and induce inflammation in an IBD-susceptible host is unresolved. To evaluate strain-level variation among tissue-associatedE. coliin the intestines, we develop a long-read sequencing approach to identify AIEC by strain that excludes host DNA. We use this approach to distinguish genetically similar strains and assess their fitness in colonizing the intestine. Here we have assembled complete genomes using long-read nanopore sequencing for a model AIEC strain, NC101, and seven strains isolated from the intestinal mucosa of Crohn’s disease and non-Crohn’s tissues. We show these strains can colonize the intestine of IBD susceptible mice and induce inflammatory cytokines from cultured macrophages. We demonstrate that these strains can be quantified and distinguished in the presence of 99.5% mammalian DNA and from within a fecal population. Analysis of global genomic structure and specific sequence variation within the ribosomal RNA operon provides a framework for efficiently tracking strain-level variation of closely-relatedE. coliand likely other commensal/pathogenic bacteria impacting intestinal inflammation in experimental settings and IBD patients.
Insulin-like Growth Factor-1 Regulates the Mechanosensitivity of Chondrocytes by Modulating TRPV4
Authors: Trompeter Nicholas , Gardinier Joseph D. , DeBarros Victor , Boggs Mary , Gangadharan Vimal , Cain William J. , Hurd Lauren , Duncan Randall L. 
Published: March 2020

ABSTRACTBoth mechanical and IGF-1 stimulation are required for normal articular cartilage development and maintenance of the extracellular matrix. While much effort has been made to define the signaling pathways associated with these anabolic stimuli, we focused on how these pathways interact to regulate chondrocyte function. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. However, the mechanism by which TRPV4 is mechanically gated or regulated is not clear. In this study we propose that insulin-like growth factor 1 (IGF-1), which is important in regulating matrix production during mechanical load, modulates TRPV4 channel activity. Our studies indicate that IGF-1 reduces hypotonic-induced TRPV4 currents, and intracellular calcium flux by increasing stress fiber formation and apparent cell stiffness. Disruption of F-actin following IFG-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Furthermore, we highlight that IGF-1 suppresses TRPV4 mediated calcium flux through the MAP7 binding domain (aa. 798-809), where actin binds to the TRPV4 channel. IGF-1 treatment differentially influences the intracellular calcium flux of HEK 293 cells stably expressing either wild-type or mutant (P799L or G800D) TRPV4 during hypotonic challenge. A key down-stream response to mechanical stimulation of chondrocytes is ATP release. Data here indicate that activation of TRPV4 through hypotonic swelling induces ATP release, but this release is greatly reduced with IGF-1 treatment. Taken together this study indicates that IGF-1 modulates TRPV4 channel response to mechanical stimulation by increasing cell stiffness. As chondrocyte response to mechanical stimulation is greatly altered during OA progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.