bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D insufficiency is prevalent in severe COVID-19
Authors: Lau Frank H. , Majumder Rinku , Torabi Radbeh , Saeg Fouad , Hoffman Ryan , Cirillo Jeffrey D. , Greiffenstein Patrick 
Published: April 2020

BackgroundCOVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients.MethodsIn an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship.ResultsTwenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic.ConclusionsVDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.
CDC50A dependent phosphatidylserine exposure induces inhibitory post-synapse elimination by microglia
Authors: Park Jungjoo , Jung Eunji , Lee Seung-Hee , Chung Won-Suk 
Published: April 2020

AbstractGlia contribute to synapse elimination through phagocytosis in the central nervous system. Despite important roles during development and neurological disorders, the “eat-me” signal that initiates glia-mediated phagocytosis of synapses remains largely elusive. Here, by generating inducible conditional knockout mice ofCdc50a, we induced stable exposure of phosphatidylserine in the neuronal outer membrane. Surprisingly, acuteCdc50adeletion in neurons causes specific loss of inhibitory post-synapses without affecting other synapses, thereby generating excessive excitability with appearance of seizure. Ablating microglia or deleting microglialMertkrescues the loss of inhibitory post-synapses, indicating that microglial phagocytosis is responsible for inhibitory post-synapse elimination. Moreover, inhibitory post-synapses in normal juvenile brains also use phosphatidylserine for synapse pruning by microglia, suggesting that phosphatidylserine may serve as a general “eat-me” signal for inhibitory post-synapse elimination.One Sentence SummaryCdc50adependent phosphatidylserine exposure functions as an “eat-me” signal for microglia-dependent inhibitory post-synapse elimination
RIT1: A Novel Biomarker in Glioblastoma
Authors: Khalil Athar , Nemer Georges 
Published: April 2020

AbstractGlioblastoma is the most common type of malignant brain tumors and the most feared cancer among adults. Its high invasiveness and the lack of successful therapies are responsible for the poor prognosis among these patients. A comprehensive understanding for the early molecular mechanisms in glioblastoma would definitely enhance its diagnosis and treatment strategies. Based on in vitro and in vivo models, it was recently postulated that the deregulated expression of key genes that are known to be involved in early neurogenesis could be the instigator of brain tumorigenesis. RIT1 (Ras Like Without CAAX 1) which encodes an unusual “orphan” GTPase protein belongs to this category of critical genes involved in controlling sequential proliferation and differentiation of adult hippocampal neural progenitor cells. As such, we surveyedRIT1expression and its potential role in glioblastoma by in-silico means. Our results revealed a significant and progressive upregulation of RIT1 expression in various publicly available datasets.RIT1expression ranked among the top upregulated genes in glioblastoma cohorts and correlated with poor overall survival. Genetic and epigenetic analysis of RIT1 didn’t reveal significant aberrations that could underlie its deregulated expression. Moreover, our results pointed onRIT1transcriptional activity that could be significantly controlled by STAT3, one of the main players in the onset of glioblastoma. In conclusion, our results are the first proof for the role of RIT1 as an oncogene in glioblastoma paving the way for its potential use as a biomarker and therapeutic target as is the case of the other members in the RAS family.
PD-1 and PD-L1 are diagnostic biomarkers and PD-L1 a promising therapeutic target in HER2-positive and triple negative normal-like feline mammary carcinoma subtypes
Authors: Nascimento Catarina , Urbano Ana Catarina , Gameiro Andreia , Ferreira João , Correia Jorge , Ferreira Fernando 
Published: April 2020

AbstractTumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. In order to understand the role of the PD- 1/PD-L1 axis in cats with mammary carcinoma, serum PD-1 and PD-L1 levels were compared with healthy controls and with serum CTLA-4 and TNF-αlevels. PD-1 and PD-L1 expression was evaluated in TILs and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p=0.017; p=0.032) and triple negative (TN) normal-like mammary carcinomas (p=0.004; p=0.015). Besides, cats presenting these tumor subtypes showed a strong positive correlation between serum PD-1, PD-L1, CTLA-4 and TNF-αlevels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p=0.010), as the percentage of PD-L1-positive TILs (p=0.038). Results from the PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T, 3.8%; V252M, 42.3%) and one in exon 5 (T267S, 3.8%). In summary, results support that serum PD-1 and PD-L1 levels can be used as diagnostic biomarkers of HER2-positive and TN normal-like feline mammary carcinomas and suggest that the development of monoclonal antibodies may be a good therapeutic strategy.
Improved estimation of hemodynamic response in fNIRS using protocol constraint and wavelet transform decomposition based adaptive algorithm
Authors: Jahani Sahar , Setarehdan Seyed Kamaledin 
Published: April 2020

BackgroundNear infrared spectroscopy allows monitoring of oxy and deoxyhemoglobin concentration changes associated with hemodynamic response function (HRF). HRF is mainly affected by physiological interferences which occur in the superficial layers of the head. This makes HRF extracting a very challenging task. Recent studies have used an additional near channel which is sensitive to the systemic interferences of the superficial layers. This additional information can be used to remove the systemic interference from the HRF.New MethodThis paper presents a novel wavelet-based constrained adaptive procedure to define the proportion of the physiological interferences in the brain hemodynamic response. The proposed method decomposes the near channel signal into several wavelet transform (WT) scales and adaptively estimates proper weights of each scale to extract their share in the HRF. The estimation of the weights are done by applying data acquisition protocol as a coefficient on recursive least square (RLS), normalized least mean square (NLMS) and Kalman filter methods.ResultsPerformance of the proposed algorithm is evaluated in terms of the mean square error (MSE) and Pearson’s correlation coefficient (R2) criteria between the estimated and the simulated HRF.Comparison with Existing MethodsResults showed that using the proposed method is significantly superior to all past adaptive filters such as EMD/EEMD based RLS/NLMS on estimating HRF signals.Conclusionswe recommend the use of WT based constraint Kalman filter in dual channel fNIRS studies with a defined protocol paradigm and using WT based Kalman filter in studies without any pre-defined protocol.
Deficiency in reverse cholesterol transport in mice augments sepsis
Authors: Wang Qian , Guo Ling , Hao Dan , Ito Misa , Yu Kai-jiang , Wang Rui-tao , Mineo Chieko , Shaul Philip W. , Li Xiang-An 
Published: April 2020

ABSTRACTBackgroundSepsis claims over 215,000 lives and costs $16.7 billion per year in America alone. Recent studies revealed that HDL receptor scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. Using Scarb1I179N mice, a mutant SR-BI mouse model with 90% depletion in hepatic SR-BI, we previously reported that the mutant mice are susceptible to cecal ligation and puncture (CLP)-induced sepsis. However, using a hypo-AlbCreSR-BIfl/fl mouse model, Huby’s group showed that the liver-specific SR-BI KO mice are not more susceptible to CLP-induced sepsis. In this study, we generated a new floxed SR-BI mouse model to clarify the contribution of hepatic SR-BI in sepsis. SR-BI is known as a receptor that plays a key role in reverse cholesterol transport (RCT) by uptaking cholesterol to the liver. So, our established AlbCreSR-BIfl/fl mice (liver-specific SR-BI KO) is an RCT deficiency mice model that can be used to understand the mechanisms of RCT protecting against sepsis and may provide new insight into the pathogenesis of sepsis.Methods and ResultsWe generated SR-BIfl/fl mice by flanking exon 2. We bred the floxed mice with AlbCre mice to generate AlbCreSR-BIfl/fl mice (liver-specific SR-BI KO mice), then the mice were backcrossed to C57BL/6J for 10 generations. As shown in Fig 1, the liver SR-BI expression was normal in SR-BIfl/fl mice as compared to C57BL/6J (B6) mice, but completely depleted in AlbCreSR-BIfl/fl mice. Using this liver-specific SR-BI KO model, we observed that a deficiency in RCT rendered the mice highly susceptible to CLP-induced sepsis as shown by 80% and 14.3% survival of SR-BIfl/fl and AlbCreSR-BIfl/fl mice, respectively. We found aggravated inflammatory cytokine production, altered leukocyte recruitment and slightly increased in the blood and peritoneal bacteria. Moreover, we found RCT deficiency mice increased both free and total cholesterol levels in serum and showed severer hemolysis in AlbCreSR-BIfl/fl mice than SR-BIfl/fl mice during CLP-induced sepsis. Importantly, when we fed AlbCreSR-BIfl/fl mice with probucol to decrease the cholesterol level in serum before performing CLP, the survival rate of AlbCreSR-BIfl/fl mice improved to 88.9%.ConclusionsDeficiency RCT resulting in abnormal metabolism of cholesterol and lipid metabolism is a risk factor in sepsis and maintain normal metabolism of cholesterol may provide a new insight for sepsis therapies.
Matrix factorization recovers consistent regulatory signals from disparate datasets
Authors: Sastry Anand V. , Hu Alyssa , Heckmann David , Poudel Saugat , Kavvas Erol , Palsson Bernhard O. 
Published: April 2020

AbstractThe availability of gene expression data has dramatically increased in recent years. This data deluge could result in detailed inference of underlying regulatory networks, but the diversity of experimental platforms and protocols introduces critical biases that could hinder scalable analysis of existing data. Here, we show that the underlying structure of theE. colitranscriptome, as determined by Independent Component Analysis (ICA), is conserved across multiple independent datasets, including both RNA-seq and microarray datasets. We also show that echoes of this structure remain in the proteome, accelerating biological discovery through multi-omics analysis. We subsequently combined five transcriptomics datasets into a large compendium containing over 800 expression profiles and discovered that its underlying ICA-based structure was still comparable to that of the individual datasets. ICA thus enables deep analysis of disparate data to uncover new insights that were not visible in the individual datasets.
NMR microsystem for label-free characterization of 3D nanoliter microtissues
Authors: Grisi Marco , Conley Gaurasundar M. , Rodriguez Kyle J. , Riva Erika , Egli Lukas , Moritz Wolfgang , Lichtenberg Jan , Brugger Jürgen , Boero Giovanni 
Published: April 2020

AbstractPerforming chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise1. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical informationin-vivois nuclear magnetic resonance (NMR)2,3. For its renowned informative power and ability to foster discoveries and life-saving applications4,5, efficient NMR at microscopic scales is highly sought after6–10, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease (NAFLD), demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.
Widespread variation in heat tolerance of the coralAcropora hyacinthusspanning variable thermal regimes across Palau
Authors: Cornwell Brendan , Hounchell Katrina , Walker Nia , Golbuu Yimnang , Nestor Victor , Palumbi Stephen R. 
Published: April 2020

ABSTRACTClimate change is poised to dramatically change ecosystem composition and productivity, leading scientists to consider the best approaches to fostering population resilience and diversity in the face of these changes. Here we present results of a large-scale experimental assessment of bleaching resistance, a critical trait for coral population persistence as oceans warm, in 293 colonies of the coralAcropora hyacinthusacross 39 reefs in Palau. We find bleaching resistant individuals originate significantly more often from warmer reefs, although they inhabit almost every reef regardless of temperature at low frequency. High levels of variationwithinreefs, where colonies experience similar temperatures, suggests that bleaching resistance is not solely due to phenotypic plasticity, but also involves adaptive alleles and host-symbiont interactions. To the extent that it is heritable, bleaching resistance could be used in promoting nursery growth, habitat restoration, or breeding, while employing large numbers of resistant colonies to preserve genetic variation.
A novel single-cell based method for breast cancer prognosis
Authors: Li Xiaomei , Liu Lin , Goodall Greg , Schreiber Andreas , Xu Taosheng , Li Jiuyong , Le Thuc Duy 
Published: April 2020

AbstractBreast cancer prognosis is challenging due to the heterogeneity of the disease. Various computational methods using bulk RNA-seq data have been proposed for breast cancer prognosis. However, these methods suffer from limited performances or ambiguous biological relevance, as a result of the neglect of intra-tumor heterogeneity. Recently, single cell RNA-sequencing (scRNA-seq) has emerged for studying tumor heterogeneity at cellular levels. In this paper, we propose a novel method,scPrognosis, to improve breast cancer prognosis with scRNA-seq data.scPrognosisuses the scRNA-seq data of the biological process Epithelial-to-Mesenchymal Transition (EMT). It firstly infers the EMT pseudotime and a dynamic gene co-expression network, then uses an integrative model to select genes important in EMT based on their expression variation and differentiation in different stages of EMT, and their roles in the dynamic gene co-expression network. To validate and apply the selected signatures to breast cancer prognosis, we use them as the features to build a prediction model with bulk RNA-seq data. The experimental results show thatscPrognosisoutperforms other benchmark breast cancer prognosis methods that use bulk RNA-seq data. Moreover, the dynamic changes in the expression of the selected signature genes in EMT may provide clues to the link between EMT and clinical outcomes of breast cancer.scPrognosiswill also be useful when applied to scRNA-seq datasets of different biological processes other than EMT.Author summaryVarious computational methods have been developed for breast cancer prognosis. However, those methods mainly use the gene expression data generated by the bulk RNA sequencing techniques, which average the expression level of a gene across different cell types. As breast cancer is a heterogenous disease, the bulk gene expression may not be the ideal resource for cancer prognosis. In this study, we propose a novel method to improve breast cancer prognosis using scRNA-seq data. The proposed method has been applied to the EMT scRNA-seq dataset for identifying breast cancer signatures for prognosis. In comparison with existing bulk expression data based methods in breast cancer prognosis, our method shows a better performance. Our single-cell-based signatures provide clues to the relation between EMT and clinical outcomes of breast cancer. In addition, the proposed method can also be useful when applied to scRNA-seq datasets of different biological processes other than EMT.
Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis
Authors: Zeng Zipeng , Huang Biao , Parvez Riana K. , Li Yidan , Chen Jyunhao , Vonk Ariel , Thornton Matthew E. , Patel Tadrushi , Rutledge Elisabeth A. , Kim Albert D. , Yu Jingying , Pastor-Soler Nuria , Hallows Kenneth R. , Grubbs Brendan H. , McMahon Jill A. , McMahon Andrew P. , Li Zhongwei 
Published: April 2020

AbstractKidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generatedde novofrom pluripotent human stem cells. UB organoids differentiate into CD organoidsin vitro, with differentiated cell types adopting spatial assemblies reflective of the adult kidney collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoidsin vitroresults in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Combining efficient gene editing with the UB organoid model will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting system.One sentence summaryCollecting duct organoids derived from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells provide anin vitroplatform for genetic dissection of development, regeneration and diseases of the mammalian collecting system.
Selection for the bacterial capsule in the absence of biotic and abiotic aggressions depends on growth conditions
Authors: Buffet Amandine , Rocha Eduardo P.C. , Rendueles Olaya 
Published: April 2020

SUMMARYExtracellular capsules protect the cell against both abiotic and biotic stresses such as bacteriophages and the host immune system. Yet, it is unclear if capsules contribute to fitness in the absence of external aggressions, in spite of the cost of production. Here, we enquire if there are conditions favouring the presence of the capsule inKlebsiella, where it is a major virulence factor. We shortly experimentally evolved 19 different strains, and show that small changes in growth media have a strong impact on the maintenance of the capsule. Competitions with capsule mutants in nine different strains showed that capsules provide ∼20% of fitness advantage in nutrient-poor conditions, due to faster growth rates and higher yields. In contrast, the capsule was readily lost in nutrient-rich media. The growth environment, as well as the capsule serotype, strongly influenced the role of the capsule in major virulence traits like hypermucoviscosity and biofilm formation. Our data shows that the capsule is selected for in situations lacking abiotic, but also biotic stresses and further supports that the capsule role in virulence may be a by-product of adaptation outside the host, hinting that it may have important roles in bacterial physiology yet to be discovered.SIGNIFICANCEBacterial capsules are a wide-spread virulence factor that limits efficacy of antimicrobial therapy. Whereas most studies focus on the role of the capsule in pathogenesis, very few have addressed the conditions under which the capsule is primarily selected for. Here, we show that small changes in growth media have a strong impact in the maintenance of the capsule and the fitness advantage they confer. Our results raise the question whether conditions lacking biotic or abiotic stresses, in addition of selecting for the maintenance of the capsule, can also play a role in selecting for serotype variation. Our results further support that the role of the capsule in virulence may be a by-product of adaptation outside the host, hinting that there may be other functionalities yet to be discovered for it.