bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant East Asian affinity of Chinese Hui genomic structure suggesting their predominant cultural diffusion model in the genetic formation process
Authors: Liu Yan , Yang Junbao , Li Yingxiang , Tang Renkuan , Yuan Didi , Wang Yicheng , Wang Peixin , Deng Shudan , Zeng Simei , Li Hongliang , Chen Gang , Zou Xing , Wang Mengge , He Guanglin 
Published: January 2021

AbstractAncestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argued that an eastward migration of Central Asian given rise to modern Hui people, which was inferred as thedemic diffusion hypothesis, and others favored thecultural diffusion hypothesisthat posited indigenous East Asian adopted Muslim-like culture and formed the modern culturally different populations. However, the extent to which the observed Hui’s genetic structure was mediated by the movement of people or the assimilation of Muslim culture also remains one of the most contentious puzzles. Analyses of over 700K SNPs in 109 western Chinese individuals (49 Sichuan Hui and 60 geographically close Nanchong Han) together with the available ancient and modern Eurasians allowed us to fully explore the genomic makeup and origin of Huis and neighboring Hans. The results of the traditional and formal admixture-statistics (PCA, ADMIXTURE, and allele-sharing-basedf-statistics) illuminated a strong genomic affinity between Sichuan Hui and Neolithic-to-modern Northern East Asians, which suggested massive gene influx from East Asian into Sichuan Hui people. Three-way admixture models in theqpWave/qpAdmanalyses further revealed a small stream of gene influx from western Eurasian related to French or Andronovo into these Hui people, which was further directly confirmed via the admixture event from the temporally different western sources to Hui people in theqpGraph-based phylogenetic model, suggesting the key role of cultural diffusion model in the genetic formation of the modern East Asian Hui. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into East Asian Hui during the historic periods, concordant with the extensive western-eastern communication in the Silk Road and historically documented Hui’s migration history. Summarily, although significant cultural differentiation among Hui and their neighbors existed, our genomic analysis showed their strong affinity with modern and ancient Northern East Asians. Our results supported that modern Chinese Hui arose from the mixture of minor western Eurasian ancestry and predominantly East Asian ancestry.
Novel CHD8 genomic targets identified in fetal mouse brain byin vivoTargeted DamID
Authors: Wade A. Ayanna , van den Ameele Jelle , Cheetham Seth W. , Yakob Rebecca , Brand Andrea H. , Nord Alex S. 
Published: January 2021

ABSTRACTGenetic studies of autism spectrum disorder (ASD) have revealed a causal role for mutations in chromatin remodeling genes. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeler with one of the highestde novomutation rates in sporadic ASD. However, the relationship between CHD8 genomic function and autism-relevant biology remains poorly elucidated. CHD8 binding studies have relied onChromatin Immunoprecipitation followed by sequencing (ChIP-seq), however, these datasets exhibit significant variability. ChIP-seq has technical limitations in the context of weak or indirect protein-DNA interactions or when high-performance antibodies are unavailable. Thus, complementary approaches are needed overall, and, specifically, to establish CHD8 genomic targets and regulatory function. Here we used Targeted DamIDin uteroto characterize CHD8 binding in developing embryonic mouse cortex. CHD8 Targeted DamID followed by sequencing (CHD8 TaDa-seq) revealed binding at previously identified targets as well as loci sensitive toChd8haploinsufficiency. CHD8 TaDa-seq highlighted CHD8 binding distal to a subset of genes specific to neurodevelopment and neuronal function. These studies establish TaDa-seq as a useful alternative for mapping protein-DNA interactionsin vivoand provide insights into the relationship between chromatin remodeling by CHD8 and autism-relevant pathophysiology associated withCHD8mutations.
An optimized FM-index library for nucleotide and amino acid search
Authors: Anderson Tim , Wheeler Travis J 
Published: January 2021

AbstractPattern matching is a key step in a variety of biological sequence analysis pipelines. The FM-index is a compressed data structure for pattern matching, with search run time that is independent of the length of the database text. We present AvxWindowedFMindex (AWFM-index), an open-source, thread-parallel FM-index library written in C that is optimized for indexing nucleotide and amino acid sequences. AWFM-index is easy to incorporate into bioinformatics software and is able to perform exact match count and locate queries ~2-4x faster than SeqAn3’s FM-index implementation for nucleotide search, and ~2-6x faster for amino acid search in a single-threaded context. This performance is due to (i) a new approach to storing FM-index data in a strided bit-vector format that enables extremely efficient computation of the FM-index occurrence function via AVX2 bitwise instructions, and (ii) inclusion of a cache-efficient lookup table for partial k-mer searches. AWFM-index also trivially parallelizes to multiple threads with good scaling, and enables efficient on-disk storage of the memory-intensive suffix array. The open-source library is available for download athttps://github.com/TravisWheelerLab/AvxWindowFmIndex.
Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer
Authors: Sivapalan Lavanya , Thorn Graeme , Gadaleta Emanuela , Kocher Hemant , Ross-Adams Helen , Chelala Claude 
Published: January 2021

AbstractThe utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in theKRASproto-oncogene. Here, we follow 3 patients with resectable disease and 4 patients with advanced unresectable disease, using exome sequencing of resected tissues and plasma samples (n=20) collected over a ∼2-year period from diagnosis through treatment to death or last follow-up. This includes 4 patients with ≥3 serial follow-up samples, of whom 2 are exceptionally long survivors (>5 years). Plasma from 3 chronic pancreatitis cases and 3 healthy controls were used as comparison for analysis of ctDNA mutations. We show that somatic mutation profiles in ctDNA are representative of matched tumour genomes. Furthermore, we detect and track ctDNA mutations within core PDAC driver genes, includingKRAS, NRAS, HRAS, TP53, SMAD4andCDKN2A, in addition to patient-specific variants within alternative cancer drivers(TP53, MTOR, ERBB2, EGFR, PBRM1, RNF43). Multiple trackable (≥ 2 plasma) ctDNA alterations with potential for therapeutic actionability in PDAC are also identified. These include variants predictive of treatment response to platinum chemotherapy and/or PARP inhibition and a unique chromosome 17 kataegis locus co-localising withERBB2driver variants and hypermutation signatures in one long-surviving patient. Finally, we demonstrate that exome profiling can facilitate the assessment of clonality within ctDNA mutations, for the determination of total ctDNA burden alongside temporal evolutionary relationships. These findings provide proof-of-concept for the use of whole exome sequencing of serial plasma samples to characterise ctDNA load and mutational profiles in patients with PDAC.
Prospective screening of liver fibrosis in a primary care cohort using systematic calculation of fib-4 in routine results
Authors: Halfon Philippe , Ansaldi Christelle , Penaranda Guillaume , Chiche Laurent , Dukan Patrick , Stavris Chloé , Plauzolles Anne , Retornaz Frédérique , Bourliere Marc 
Published: January 2021

AbstractBackground & AimLiver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis.MethodsBetween December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhône region.ResultsAmong the 29 707 patients, 2160 (7.3%) had significant fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1267 (1267/2160: 59%) patients who were not managed for any liver disease.ConclusionsThis work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Clinical Registering NumberMR-0314071019 (INDS: French National Institute for Medical Data)
ImplementingEssential Coaching for EveryMother during COVID-19: A Pilot Pre-Post Intervention Study
Authors: Dol Justine , Aston Megan , Grant Amy , McMillan Douglas , Murphy Gail Tomblin , Campbell-Yeo Marsha 
Published: January 2021

AbstractObjectivesThe primary objective was to evaluate the preliminary impact ofEssential Coaching for Every Motheron self-efficacy, social support, postpartum anxiety and postpartum depression. The second objective was to explore the acceptability of theEssential Coaching for Every Motherprogram provided during the COVID-19 pandemic.MethodsA prospective pre-post study was conducted with first time mothers in Nova Scotia, Canada between July 15thand September 19th, 2020. Participants completed a self-report survey at enrolment (after birth) and six-weeks postpartum. Various standardized measures were used and qualitative feedback on the program was also collected. Paired t-tests were carried out to determine changes from baseline to follow-up on psychosocial outcomes and qualitative feedback was analysed through thematic analysis.ResultsA total of 88 women enrolled. Self-efficacy increased between baseline (B) and follow-up (F) (B:33.33;F:37.11,p=0.000) while anxiety (STAI) declined (B:38.49;F:34.79; p=0.004). In terms of acceptability, 89% of participants felt that the number of messages were just right, 84.5% felt the messages contained all the information they needed relative to caring for a newborn and 98.8% indicated they would recommend this program to other new mothers.ConclusionEssential Coaching for Every Mothermay play a role in increasing maternal self-efficacy and decreasing anxiety, although future work with a control group is needed to delineate the true effects of the program. Overall, mothers were satisfied with theEssential Coaching for Every Motherprogram and would recommend it for other mothers, during COVID-19 and beyond.
A Novel Multiplex PCR Based Detection Assay Using Saliva or Nasopharyngeal Samples for SARS-Cov-2, Influenza A and B – Clinical Validation and Utility for Mass Surveillance
Authors: Sahajpal Nikhil S , Mondal Ashis K , Ananth Sudha , Njau Allan , Ahluwalia Pankaj , Oza Eesha , Ross Ted M , Kota Vamsi , Kothandaraman Arvind , Fulzele Sadanand , Hegde Madhuri , Chaubey Alka , Rojiani Amyn M , Kolhe Ravindra 
Published: January 2021

AbstractBackgroundThe COVID-19 pandemic has resulted in a significant diversion of human and material resources to COVID-19 diagnostics, to the extent that testing of viral pathogens normally contributing to seasonal respiratory tract infections have been markedly neglected. The global health burden due to influenza viruses and co-infection in COVID-19 patients remains undocumented but clearly pose serious public health consequences. To address these clinical and technical challenges, we have optimized and validated a highly sensitive RT-PCR based multiplex assay for the detection of SARS-CoV-2, Influenza A and B viruses in a single test.MethodsThis study evaluated clinical specimens (n=1411) that included 1019 saliva and 392 nasopharyngeal swab (NPS) samples collected in either healthcare or community setting. Samples were tested using two assays: FDA-EUA approved SARS-CoV-2 assay that targets N and ORF1ab gene, and the PKamp RT-PCR based assay that targets SARS-CoV-2, Influenza viruses A and B. The limit of detection (LoD) studies was conducted as per the FDA guidelines using SARS-CoV-2 and Influenza A and B reference control materials.ResultsOf the 1019 saliva samples, 17.0% (174/1019) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [91.9% (160/174) vs. 87.9% (153/174)], respectively. Of the 392 NPS samples, 10.4% (41/392) tested positive for SARS-CoV-2 using either assay. The detection rate for SARS-CoV-2 was higher with our multiplex assay compared to SARS-specific assay [97.5% (40/41) vs. 92.1% (39/41)], respectively. The Ct values for SARS-CoV-2 were comparable between the two assays, whereas the Ct values of the housekeeping gene was significantly lower with multiplex assay compared to SARS-specific assay. The LoD was established as 60 copies/ml for SARS-CoV-2 and 180 copies/ml for Influenza A and B viruses for both saliva and NPS samples.ConclusionThis study presents clinical validation of a multiplex PCR assay for testing SARS-CoV-2, Influenza A and B viruses, using NPS and saliva samples, and demonstrates the feasibility of implementing the assay without disrupting the existing laboratory workflow. This novel assay uses the same instruments, sample types, supplies, and laboratory personnel as needed for the testing of SARS-CoV-2 virus.
Smartphone-based digital biomarkers for Parkinson’s disease in a remotely-administered setting
Authors: Goñi María , Eickhoff Simon B. , Far Mehran Sahandi , Patil Kaustubh R. , Dukart Juergen 
Published: January 2021

ABSTRACTSmartphone-based digital biomarker (DB) assessments provide objective measures of daily-life tasks and thus hold the promise to improve diagnosis and monitoring of Parkinson’s disease (PD). To date, little is known about which tasks perform best for these purposes and how different confounds including comorbidities, age and sex affect their accuracy. Here we systematically assess the ability of common self-administered smartphone-based tasks to differentiate PD patients and healthy controls (HC) with and without accounting for the above confounds. Using a large cohort of PD patients and healthy volunteers acquired in the mPower study, we extracted about 700 features commonly reported in previous PD studies for gait, balance, voice and tapping tasks. We perform a series of experiments systematically assessing the effects of age, sex and comorbidities on the accuracy of the above tasks for differentiation of PD patients and HC using several machine learning algorithms. When accounting for age, sex and comorbidities, the highest balanced accuracy on hold-out data (73%) was achieved using random forest when combining all tasks followed by tapping using relevance vector machine (67%). Only moderate accuracies were achieved for other tasks (60% for balance, 56% for gait and 53% for voice data). Not accounting for the confounders consistently yielded higher accuracies of up to 77% when combining all tasks. Our results demonstrate the importance of controlling DB data for age and comorbidities.
Mass Testing with Contact Tracing Compared to Test and Trace for Effective Suppression of COVID-19 in the UK: A rapid review
Authors: Mbwogge Mathew 
Published: January 2021

AbstractBackgroundMaking testing available to everyone and tracing contacts might be the gold standard towards the control of COVID-19, particularly when significant transmissions are without symptoms. This study evaluated the effectiveness of mass testing and contact tracing in the suppression of COVID-19 compared to conventional Test and Trace in the UK.DesignA rapid review of available evidencePrimary research questionIs there evidence that mass testing and tracing could suppress community spread of SARS-CoV-2 infections better than Test and Trace?Secondary research questionWhat is the proportion of asymptomatic cases of SARS-CoV-2 reported during mass testing interventions?MethodsLiterature was searched in September through December 2020 in Google Scholar, ScienceDirect, Mendeley and PubMed.ResultsLiterature search yielded 286 articles from Google Scholar, 20 from Science Direct, 14 from Mendeley, 27 from Pubmed and 15 through manual search. Altogether 35 articles were included, making a sample size of close to a million participants.ConclusionThere was a very low level but promising evidence of 76.9% (95% CI: 46.2 – 95.0, P=0.09) majority vote in favour of the intervention under the primary objective. The overall proportion of asymptomatic cases among those tested positive and tested sample populations under the secondary objective was 40.7% (95% CI: 38.8– 42.5) and 0.01% (95% CI: 0.01 – 0.012) respectively. Conventional test and trace should be superseded by a decentralised and regular mass rapid testing and contact tracing, championed by GP surgeries and low cost community services.
Optimal piecewise constant vaccination and lockdown policies for COVID-19
Authors: Salcedo-Varela Gabriel A. , Peñuñuri F. , González-Sánchez D. , Díaz-Infante Saúl 
Published: January 2021

AbstractWe formulate a controlled system of ordinary differential equations, with vaccination and lockdown interventions as controls, to simulate the mitigation of COVID-19. The performance of the controls is measured through a cost functional involving vaccination and lockdown costs as well as the burden of COVID19 quantified in DALYs. We calibrate parameters with data from Mexico City and Valle de Mexico. By using differential evolution, we minimize the cost functional subject to the controlled system and find optimal policies that are constant in time intervals of a given size. The main advantage of these policies relies on its practical implementation since the health authority has to make only a finite number of different decisions. Our methodology to find optimal policies is relatively general, allowing changes in the dynamics, the cost functional, or the frequency the policymaker changes actions.
Systematic identification of cis-interacting lncRNAs and their targets
Authors: Agrawal Saumya , Kulakovskiy Ivan V. , Severin Jessica , Koido Masaru , Alam Tanvir , Abugessaisa Imad , Buyan Andrey , Chang Howard Y. , Dostie Josee , Itoh Masayoshi , Kere Juha , Kondo Naoto , Li Yunjing , Makeev Vsevolod J. , Mendez Mickaël , Okazaki Yasushi , Ramilowski Jordan A. , Sigorskikh Andrey I. , Strug Lisa J. , Yagi Ken , Yasuzawa Kayoko , Yip Chi Wai , Hon Chung Chau , Hoffman Michael M. , Terao Chikashi , Kasukawa Takeya , Shin Jay W. , Carninci Piero , de Hoon Michiel JL 
Published: January 2021

AbstractThe human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Studying lncRNAs is challenging due to their low expression level, cell type-specific occurrence, poor sequence conservation between orthologs, and lack of information about RNA domains. LncRNAs direct the regulatory factors in the locations that are in cis to their transcription sites. We designed a model to predict if an lncRNA acts in cis based on its features and trained it using RNA-chromatin interaction data. The trained model is cell type-independent and does not require RNA-chromatin data. Combining RNA-chromatin and Hi-C data, we showed that lncRNA-chromatin binding sites are determined by chromosome conformation. For each lncRNA, the spatially proximal genes were identified as their potential targets by combining Hi-C and Cap Analysis Gene Expression (CAGE) data in 18 human cell types. RNA-protein and RNA-chromatin interaction data suggested that lncRNAs act as scaffolds to recruit regulatory proteins to target promoters and enhancers. We provide the data through an interactive visualization web portal athttps://fantom.gsc.riken.jp/zenbu/reports/#F6_3D_lncRNA.
Inferring long-term effective population size with Mutation-Selection models
Authors: Latrille T. , Lanore V. , Lartillot N. 
Published: January 2021

AbstractMutation-selection phylogenetic codon models are grounded on population genetics first principles and represent a principled approach for investigating the intricate interplay between mutation, selection and drift. In their current form, mutation-selection codon models are entirely characterized by the collection of site-specific amino-acid fitness profiles. However, thus far, they have relied on the assumption of a constant genetic drift, translating into a unique effective population size (Ne) across the phylogeny, clearly an unreasonable hypothesis. This assumption can be alleviated by introducing variation inNebetween lineages. In addition toNe, the mutation rate (μ) is susceptible to vary between lineages, and both should co-vary with life-history traits (LHTs). This suggests that the model should more globally account for the joint evolutionary process followed by all of these lineage-specific variables (Ne,μ, and LHTs). In this direction, we introduce an extended mutation-selection model jointly reconstructing in a Bayesian Monte Carlo framework the fitness landscape across sites and long-term trends inNe,μand LHTs along the phylogeny, from an alignment of DNA coding sequences and a matrix of observed LHTs in extant species. The model was tested against simulated data and applied to empirical data in mammals, isopods and primates. The reconstructed history ofNein these groups appears to correlate with LHTs or ecological variables in a way that suggests that the reconstruction is reasonable, at least in its global trends. On the other hand, the range of variation in Ne inferred across species is surprisingly narrow. This last point suggests that some of the assumptions of the model, in particular concerning the assumed absence of epistatic interactions between sites, are potentially problematic.
Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation
Authors: Eriksson David , Schneider Artur , Thirumalai Anupriya , Alyahyay Mansour , de la Crompe Brice , Sharma Kirti , Ruther Patrick , Diester Ilka 
Published: January 2021

SummarySimultaneous large-scale recordings and optogenetic interventions hold the promise to decipher the fast-paced and multifaceted dialogue between neurons that sustains brain function. Here we developed unprecedentedly thin, cell-sized Lambertian side-emitting optical fibers and combined them with silicon probes to achieve high quality recordings and ultrafast multichannel optogenetic inhibition in freely moving animals. Our new framework paves the way for large-scale photo tagging and controlled interrogation of rapid neuronal communication in any combination of brain areas.HighlightsTo combine large-scale recordings with optical perturbation we have developed a number of new techniques such as thin optical side-emitting fibers, a fiber matrix connector for thin fibers, an electro-optical commutator for multiple thin fibers, an active patch cord, a flexible fiber bundle ribbon cable, and a modular multi-optrode implantation holder.