bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental health service activity during COVID-19 lockdown among individuals with potential neurodevelopmental disorders: South London and Maudsley data on services and mortality from January to July 2020
Authors: Martin Evangelia , Nuzum Eleanor , Broadbent Matthew , Stewart Robert 
Published: October 2020

AbstractThe lockdown and social distancing policy imposed due to the COVID-19 pandemic is likely to have had a widespread impact on mental healthcare service provision and use. Previous reports from the South London and Maudsley NHS Trust (SLaM; a large mental health service provider for 1.2m residents in South London) highlighted a shift to virtual contacts among those accessing community mental health and home treatment teams and an increase in deaths over the pandemic’s first wave. However, there is a need to quantify this for individuals with particular vulnerabilities, including those with learning disabilities and other neurodevelopmental disorders. Taking advantage of the Clinical Record Interactive Search (CRIS) data resource with 24-hourly updates of electronic mental health records data, this paper describes daily caseloads and contact numbers (face-to-face and virtual) for individuals with potential neurodevelopmental disorders across community, specialist, crisis and inpatient services. The report focussed on the period 1st January to 31st July 2020. We also report on daily accepted and discharged trust referrals, total trust caseloads and daily inpatient admissions and discharges for individuals with potential neurodevelopmental disorders. In addition, daily deaths are described for all current and previous SLaM service users with potential neurodevelopmental disorders over this period. In summary, comparing periods before and after 16th March 2020 there was a shift from face-to-face contacts to virtual contacts across all teams. The largest declines in caseloads and total contacts were seen in Home Treatment Team, Liaison/A&E and Older Adult teams. Reduced accepted referrals and inpatient admissions were observed and there was an 103% increase in average daily deaths in the period after 16th March, compared to the period 1st January to 15th March (or a 282% increase if the 2-month period from 16th March to 15th May was considered alone).
Findings from serological surveys (in August 2020) to assess the exposure of adult population to SARS Cov-2 infection in three cities of Odisha, India
Authors: Kshatri Jaya Singh , Bhattacharya Debdutta , Kanungo Srikanta , Giri Sidhartha , Palo Subrata Kumar , Parai Debaprasad , Turuk Jyotirmayee , Mansingh Asit , Choudhary Hariram , Dash Girish Chandra , Mishra Niranjan , Satapathy D.M. , Sahoo Sanjaya Ku , Pati Sanghamitra 
Published: October 2020

AbstractBackgroundThere is always an uncertainty of epidemiological, serological infectivity and virulence of the emerging novel coronavirus. Antibody test can be used for assessing whether immunity has developed in the infected person after 5-7 days of illness and understand cumulative exposure levels to the infection, make inferences on the actual burden of infection, its geographical spread, effect on specific demographic/risk groups, gaps in testing and infection fatality rates.ObjectiveTo estimate and compare the sero-prevalence, hidden prevalence and determine the demographic risk factors associated with SARS-CoV-2 infection among adults in three largest cities of Odisha, India.MethodologyThis was a population based cross sectional serological survey carried out in August 2020 in the three largest cities of the state of Odisha. Sample size per city was estimated to be 1500 and participants were enrolled from the community using multi-stage random sampling from 25 clusters from each city. Data was collected using ODK based tools by household visits and 3-4 ml of blood samples were collected after informed consent. Samples were transported to testing lab where Serum was separated and tested for anti-SARS CoV-2 antibodies using automated CLIA platform. Statistical analysis was done using R-software packages.ResultsA total of 4146 participants from the 3 cities of Bhubaneswar (BBS), Berhampur (BAM) and Rourkela (RKL) participated. A total of 5635 households were approached and the average non response rate in the community was 17.4%. The gender weighted seroprevalence across the three cities was 20.78% (95% CI: 19.56%-22.05%). Seroprevalence was highest in BAM at 31.14% (95% CI: 28.69-33.66%) followed by 24.59% (95% CI: 22.39-26.88%) in RKL and 5.24% (95% CI: 4.10-6.58%) in BBS. While females reported a higher seroprevalence (22.8%) as compared to males (18.8%), there was no significant difference in seroprevalence across age groups. A majority of the seropositive participants were asymptomatic (93.87%). Among those who reported symptoms, the most common symptom was fever (68.89%) followed by cough (46.06%) and myalgia (32.67%). The case to infection ratio on the date of serosurvey was 1: 6.6 in BBS, 1:61 in BAM and 1:29.8 in RKL.ConclusionThe study found a high seroprevalence against COVID-19 in urban Odisha as well as high numbers of asymptomatic infections.
Are the SIR and SEIR models suitable to estimate the basic reproduction number for the CoViD-19 epidemic?
Authors: Yang Hyun Mo , Lombardi Junior Luis Pedro , Yang Ariana Campos 
Published: October 2020

AbstractThe transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes pandemic but presents different incidences in the world. Mathematical models were formulated to describe the coronavirus disease 2019 (CoViD-19) epidemic in each country or region. At the beginning of the pandemic, many authors used the SIR (susceptible, infectious, and recovered compartments) and SEIR (including exposed compartment) models to estimate the basic reproduction numberR0for the CoViD-19 epidemic. These simple deterministic models assumed that the only available collection of the severe CoViD-19 cases transmitted the SARS-CoV-2 and estimated lower values forR0, ranging from 1.5 to 3.0. However, the major flaw in the estimation ofR0provided by the SIR and SEIR models was that the severe CoViD-19 patients were hospitalized, and, consequently, not transmitting. Hence, we proposed a more elaborate model considering the natural history of CoViD-19: the inclusion of asymptomatic, pre-symptomatic, mild and severe CoViD-19 compartments. The model also encompassed the fatality rate depending on age. This SEAPMDR model estimatedR0using the severe CoViD-19 data from São Paulo State (Brazil) and Spain, yielding higher values forR0, that is, 6.54 and 5.88, respectively. It is worth stressing that this model assumed that severe CoViD-19 cases were not participating in the SARS-CoV-2 transmission chain. Therefore, the SIR and SEIR models are not suitable to estimateR0at the beginning of the epidemic by considering the isolated severe CoViD-19 data as transmitters.
Determining subpopulation methylation profiles from bisulfite sequencing data of heterogeneous samples using DXM
Authors: Fong Jerry , Gardner Jacob R. , Andrews Jared M. , Cashen Amanda F. , Payton Jacqueline E. , Weinberger Kilian Q. , Edwards John R. 
Published: October 2020

ABSTRACTEpigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM’s performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM to a cohort of 31 DLBCLs and relate allelic subpopulation methylation profiles to relapse. We thus demonstrate that DXM can robustly find allelic subpopulation methylation profiles that may contribute to disease progression using bisulfite sequencing data of any heterogeneous sample.
LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency
Authors: O’Connor Marie N. , Kallenberg David M. , Jackstadt Rene , Watson Angharad H. , Alatsatianos Markella , Ohme Julia , Camilli Carlotta , Pilotti Camilla , Dritsoula Athina , Bowers Chantelle E. , Dowsett Laura , George Jestin , Wang Xiaomeng , Ager Ann , Sansom Owen J. , Moss Stephen E. , Greenwood John 
Published: October 2020

ABSTRACTVascular dysfunction contributes to the pro-oncogenic tumor microenvironment and impedes the delivery of therapeutics. Normalizing of the tumor vasculature has therefore become a potential therapeutic objective. We previously reported that the secreted glycoprotein, leucine-rich α-2-glycoprotein 1 (LRG1), contributes to the formation of pathogenic neovascularization. Here we show that in mouse models of cancer,Lrg1is induced in tumor endothelial cells. We demonstrate that the expression of LRG1 impacts on tumor progression asLrg1deletion or treatment with a LRG1 function-blocking antibody inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function resulting in significantly enhanced efficacy of cisplatin chemotherapy, adoptive T-cell therapy and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent (cold) to immune active (hot). LRG1 therefore drives vascular abnormalization and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics.
Integrated analysis of multimodal single-cell data
Authors: Hao Yuhan , Hao Stephanie , Andersen-Nissen Erica , Mauck William M. , Zheng Shiwei , Butler Andrew , Lee Maddie J. , Wilk Aaron J. , Darby Charlotte , Zagar Michael , Hoffman Paul , Stoeckius Marlon , Papalexi Efthymia , Mimitou Eleni P. , Jain Jaison , Srivastava Avi , Stuart Tim , Fleming Lamar B. , Yeung Bertrand , Rogers Angela J. , McElrath Juliana M. , Blish Catherine A. , Gottardo Raphael , Smibert Peter , Satija Rahul 
Published: October 2020

AbstractThe simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on multiple data types. Here, we introduce ‘weighted-nearest neighbor’ analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of hundreds of thousands of human white blood cells alongside a panel of 228 antibodies to construct a multimodal reference atlas of the circulating immune system. We demonstrate that integrative analysis substantially improves our ability to resolve cell states and validate the presence of previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets, and to interpret immune responses to vaccination and COVID-19. Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets, including paired measurements of RNA and chromatin state, and to look beyond the transcriptome towards a unified and multimodal definition of cellular identity.AvailabilityInstallation instructions, documentation, tutorials, and CITE-seq datasets are available athttp://www.satijalab.org/seurat
A CRISPR interference platform for selective downregulation of gene expression inBorrelia burgdorferi
Authors: Takacs Constantin N. , Scott Molly , Chang Yunjie , Kloos Zachary A. , Irnov Irnov , Rosa Patricia A. , Liu Jun , Jacobs-Wagner Christine 
Published: October 2020

ABSTRACTThe spirocheteBorrelia burgdorfericauses Lyme disease, an increasingly prevalent infection. While previous studies have provided important insight intoB. burgdorferibiology, many aspects, including basic cellular processes, remain underexplored. To help speed up the discovery process, we adapted a CRISPR interference (CRISPRi) platform for use inB. burgdorferi. For efficiency and flexibility of use, we generated various CRISPRi template constructs that produce different basal and induced levels ofdcas9and carry different antibiotic resistance markers. We characterized the effectiveness of our CRISPRi platform by targeting the motility and cell morphogenesis genesflaB, mreB, rodA,andftsI,whose native expression levels span two orders of magnitude. For all four genes, we obtained gene repression efficiencies of at least 95%. We showed by darkfield microscopy and cryo-electron tomography that flagellin (FlaB) depletion reduced the length and number of periplasmic flagella, which impaired cellular motility and resulted in cell straightening. Depletion of FtsI caused cell filamentation, implicating this protein in cell division inB. burgdorferi. Finally, localized cell bulging in MreB- and RodA-depleted cells matched the locations of new peptidoglycan insertion specific to spirochetes of theBorreliagenus. These results therefore implicate MreB and RodA in the particular mode of cell wall elongation of these bacteria. Collectively, our results demonstrate the efficiency and ease of use of ourB. burgdorferiCRISPRi platform, which should facilitate future genetic studies of this important pathogen.IMPORTANCEGene function studies are facilitated by the availability of rapid and easy-to-use genetic tools. Homologous recombination-based methods traditionally used to genetically investigate gene function remain cumbersome to perform inB. burgdorferi, as they often are relatively inefficient. In comparison, our CRISPRi platform offers an easy and fast method to implement as it only requires a single plasmid transformation step and IPTG addition to obtain potent (>95%) downregulation of gene expression. To facilitate studies of various genes in wild-type and genetically modified strains, we provide over 30 CRISPRi plasmids that produce distinct levels ofdcas9expression and carry different antibiotic resistance markers. Our CRISPRi platform represents a useful and efficient complement to traditional genetic and chemical methods to study gene function inB. burgdorferi.
Codon usage pattern reveals SARS-CoV-2 as a monomorphic pathogen of hybrid origin with role of silent mutations in rapid evolutionary success
Authors: Bansal Kanika , Kumar Sanjeet , Patil Prabhu B. 
Published: October 2020

AbstractViruses are dependent on the host tRNA pool, and an optimum codon usage pattern (CUP) is the driving force in its evolution. Systematic analysis of CUP of the coding sequences (CDS) of representative major pangolin lineages A and B of SARS-CoV-2 indicate a single transmission event of a codon-optimized virus from its source into humans. Here, no direct congruence could be detected in CUP of all CDS of SARS-CoV-2 with the non-human natural SARS viruses further reiterating its novelty. Several CDS show similar CUP with bat or pangolin, while others have distinct CUP pointing towards a possible hybrid nature of the virus. At the same time, phylogenetic diversity suggests the role of even silent mutations in its success by adapting to host tRNA pool. However, genomes of SARS-CoV-2 from primary infections are required to investigate the origins amongst the competing natural or lab leak theories.
A Systematic Review and Meta-analysis for Association of Helicobacter pylori Colonization and Celiac Disease
Authors: Amlashi Fazel Isapanah , Norouzi Zahra , Sohrabi Ahmad , Shirzad-Aski Hesamaddin , Norouzi Alireza , Ashkbari Ali , Gilani Naghme , Fatemi Seyed Alireza , Besharat Sima 
Published: October 2020

AbstractBackground and objectivesBased on some previous observational studies there is a theory that suggests a potential relationship between Helicobacter pylori (H. pylori) colonization and celiac disease (CD), however, the type of this relationship is still controversial. Therefore, we aimed to conduct a systematic review and meta-analysis to explore all related primary studies to find any possible association between CD and human H. pylori colonization.Data sourcesStudies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After screening, the quality and risk of bias assessment of the selected articles were evaluated.Synthesis methodsMeta-analysis calculated pooled odds ratio (OR) on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed.ResultsTwenty-four studies were included in this systematic review, with a total of 5241 cases and 132947 control people. The results of meta-analysis on 24 studies showed a significant and negative association between H. pylori colonization and CD (pooled OR= 0.58; 95% CI = 0.45 - 0.76; P < 0.001), with no publication bias (P = 0.407). The L’Abbé plots also showed a trend of having more H. pylori colonization in the control group. Among subgroups, ORs were notably different only when the data were stratified by continents or risk of bias; however, subgroup analysis could not determine the source of heterogeneity.ConclusionsAccording to the meta-analysis, H. pylori has a mild protective role toward CD. Although this negative association is not strong, it is statistically significant and should be further considered. Further investigations in both molecular and clinic fields with proper methodology and more detailed information are needed to discover more evidence and underlying mechanisms to clear the interactive aspects of H. pylori colonization in CD patients.Systematic review registration number (PROSPERO)CRD42020167730
Targeted-Antibacterial-Plasmids (TAPs) combining conjugation and CRISPR/Cas systems achieve strain-specific antibacterial activity
Authors: Reuter Audrey , Hilpert Cécile , Dedieu-Berne Annick , Lematre Sophie , Gueguen Erwan , Launay Guillaume , Bigot Sarah , Lesterlin Christian 
Published: October 2020

AbstractThe global emergence of drug-resistant bacteria leads to the loss of efficacy of our antibiotics arsenal and severely limits the success of currently available treatments. Here, we developed an innovative strategy based on Targeted-Antibacterial-Plasmids (TAPs) that use bacterial conjugation to deliver CRISPR/Cas systems exerting a strain-specific antibacterial activity. TAPs are highly versatile as they can be directed against any specific genomic or plasmid DNA using the custom algorithm (CSTB) that identifies appropriate targeting spacer sequences. We demonstrate the ability of TAPs to induce strain-selective killing by introducing lethal double strand breaks (DSBs) into the targeted genomes. TAPs directed against a plasmid-born carbapenem resistance gene efficiently resensitise the strain to the drug. This work represents an essential step towards the development of an alternative to antibiotic treatments, which could be used forin situmicrobiota modification to eradicate targeted resistant and/or pathogenic bacteria without affecting other non-targeted bacterial species.
The Himalayan Uplift and the Evolution of Aquatic Biodiversity Across Asia: Snowtrout (Cyprininae: Schizothorax) as a Test Case
Authors: Regmi Binod , Douglas Marlis R. , Edds David R. , Wangchuk Karma , Lu Chang , Khanal Gopal Prasad , Norbu Pema , Norbu Sangay , Dorji Sonam , Tshering Singye , Angel Zachary , Chafin Tyler K. , Zbinden Zachery D. , Douglas Michael E. 
Published: October 2020

The Himalayan uplift, a tectonic event of global importance, seemingly disseminated aquatic biodiversity broadly across Asia. But surprisingly, this hypothesis has yet to be tested. We do so herein by sequencing 1,140 base-pair of mtDNA cytochrome-b for 72 tetraploid Nepalese/Bhutanese Snowtrout (Schizothorax spp.), combining those data with 67 GENBANK® sequences (59 ingroup/8 outgroup), then reconstructing phylogenetic relationships using maximum likelihood/ Bayesian analyses. Results indicate Snowtrout originated in Central Asia, dispersed across the Qinghai-Tibetan Plateau (QTP), then into Bhutan via south-flowing tributaries of the east-flowing Yarlung-Tsangpo River (YLTR). The headwaters of five large Asian rivers provided dispersal corridors into southeast Asia. South of the Himalaya, the YLTR transitions into a westward-flowing Brahmaputra River that facilitated successive colonization of Himalayan drainages: First Bhutan, then Nepal, followed by far-western drainages subsequently captured by the Indus River. We found greater species-divergences across rather than within-basins, implicating vicariant evolution as a driver. The Himalaya is a component of the “third-pole” [Earth’s largest (but rapidly shrinking) glacial reservoir outside the Arctic/Antarctic]. Its unique aquatic biodiversity must not only be recognized (as herein) but also conserved through broad, trans-national collaborations. Our results effectively contrast phylogeography with taxonomy as a necessary first step in this process.The Himalaya is the most extensive and recently evolved mountain system on Earth (length=2400km; width=240km; elevation=75-8800m), with a global significance underscored by its large-scale lithospheric, cryospheric, and atmospheric interactions [1]. These have not only driven global climate, but also defined the cultural and biological endemism of the region [2]. Massive, tectonically derived mountain chains such as the Alps and the Himalaya are hypothesized as being fundamental to the formation of global biodiversity gradients via vicariance and local adaptation, with a significantly stronger signal in terrestrial rather than aquatic systems [3]. Here we test how orogeny (the deformation and folding of Earth’s crust by lateral compression) has contributed to the diversification of freshwater fishes broadly across Asia. We do so by evaluating the phylogeography of an endemic high-elevation fish, the Snowtrout (Schizothorax: Cyprinidae).
Conserved and divergent aspects of Robo receptor signaling and regulation betweenDrosophilaRobo1 andC. elegansSAX-3
Authors: Daiber Trent , VanderZwan-Butler Christine J. , Bashaw Greg J. , Evans Timothy A. 
Published: October 2020

AbstractThe evolutionarily conserved Roundabout (Robo) family of axon guidance receptors control midline crossing of axons in response to the midline repellant ligand Slit in bilaterian animals including insects, nematodes, and vertebrates. Despite this strong evolutionary conservation, it is unclear whether the signaling mechanism(s) downstream of Robo receptors are similarly conserved. To directly compare midline repulsive signaling in Robo family members from different species, here we use a transgenic approach to express the Robo family receptor SAX-3 from the nematodeCaenorhabditis elegansin neurons of the fruit fly,Drosophila melanogaster. We examine SAX-3’s ability to repelDrosophilaaxons from the Slit-expressing midline in gain of function assays, and test SAX-3’s ability to substitute forDrosophilaRobo1 during fly embryonic development in genetic rescue experiments. We show thatC. elegansSAX-3 is properly translated and localized to neuronal axons when expressed in theDrosophilaembryonic CNS, and that SAX-3 can signal midline repulsion inDrosophilaembryonic neurons, although not as efficiently asDrosophilaRobo1. Using a series of Robo1/SAX-3 chimeras, we show that the SAX-3 cytoplasmic domain can signal midline repulsion to the same extent as Robo1 when combined with the Robo1 ectodomain. We show that SAX-3 is not subject to endosomal sorting by the negative regulator Commissureless (Comm) inDrosophilaneuronsin vivo, and that peri-membrane and ectodomain sequences are both required for Comm sorting ofDrosophilaRobo1.