bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population
Authors: Lim Charlie G.Y. , Ozkan Bige , Liang Yujian , Yao Jiali , Khaing Nang Ei Ei , Rooney Mary R. , Ndumele Chiadi E. , Tai E Shyong , Coresh Josef , Sim Xueling , van Dam Rob M. 
Published: July 2023

AbstractThe molecular mechanisms connecting obesity and cardiometabolic diseases are not fully understood. We evaluated the associations between body mass index (BMI), waist circumference (WC), and ∼5,000 plasma proteins in the Singapore Multi-Ethnic Cohort (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent dataset across two timepoints and externally in the Atherosclerosis Risk in Communities (ARIC) study. The BMI- and WC-protein signatures were highly correlated with total and visceral body fat, respectively. Furthermore, the protein signatures were significantly associated with cardiometabolic risk factors and were able to differentiate between metabolically healthy and unhealthy obesity. In prospective analyses, the protein signatures were strongly associated with type 2 diabetes risk in MEC1 (odds ratio per SD increment in WC-protein signature = 2.84, 95% CI 2.47 to 3.25) and ARIC (hazard ratio = 1.97, 95% CI 1.87 to 2.07). Pathways related to cell signaling, systemic inflammation, and glucose and fat metabolism were overrepresented in the BMI- and WC-protein signatures. Our protein signatures have potential uses for the monitoring of metabolically unhealthy obesity.Article HighlightsWe evaluated the associations between ∼5000 plasma proteins and BMI and WC in a multi-ethnic Asian population.We identified 410 proteins associated with BMI and 385 proteins associated with WC and derived protein signatures of BMI and WC, which we validated externally in a US cohort.Both the BMI- and WC-protein signatures were strongly associated with cardiometabolic risk factors and the risk of type 2 diabetes and were enriched in pathways relating to cell signaling, systemic inflammation, and glucose and fat metabolism.Our protein signatures have potential uses for monitoring metabolically unhealthy obesity.
On the detectability and accuracy of computational measurements of enlarged perivascular spaces from magnetic resonance images
Authors: Coello Roberto Duarte , Valdés Hernández Maria del C. , Zwanenburg Jaco J.M. , van der Velden Moniek , Kuijf Hugo J. , De Luca Alberto , Moyano José Bernal , Ballerini Lucia , Chappell Francesca M. , Brown Rosalind , Biessels Geert Jan , Wardlaw Joanna M. 
Published: July 2023

AbstractMagnetic Resonance Imaging (MRI) visible perivascular spaces (PVS) have been associated with age, decline in cognitive abilities, interrupted sleep, and markers of small vessel disease. Therefore, several computational methods have been developed for their assessment from brain MRI. But the limits of validity of these methods under various spatial resolutions, and the accuracy in detecting and measuring the dimensions of these structures have not been established. We use a digital reference object (DRO) previously developed for this purpose, to construct anin-silicophantom for answering these questions; and validate it using a physical phantom. Ourin-silicoand physical phantoms use cylinders of different sizes as models for PVS. Using both phantoms, we also evaluate the influence of the “PVS” orientation on the accuracy of the diameter measured, different sets of parameters for two vesselness filters that have been used for enhancing tubular structures, namely Frangi and RORPO filters, and the influence of the vesselness filterper-sein the accuracy of the measurements. Our experiments indicate that PVS measurements in MRI are only a proxy of their true dimensions, as the boundaries of their representation are consistently overestimated. The success in the use of the Frangi filter for this task relies on a careful tuning of several parameters. The combination of parameters α=0.5, β=0.5 and c=500 proved to yield the best results. RORPO, on the contrary, does not have these requirements, and allows detecting smaller cylinders in their entirety more consistently in the ideal scenarios tested. The segmentation of the cylinders using the Frangi filter seems to be best suited for voxel sizes equal or larger than 0.4 mm-isotropic and cylinders larger than 1 mm diameter and 2 mm length. “PVS” orientation did not influence their measures for image data with isotropic voxel size. Further evaluation of the emerging deep-learning methods is still required, and these results should be tested in “real” world data across several diseases.
KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution
Authors: Reis de Andrade J. , Scourfield E. , Peswani-Sajnani S. , Poulton K. , Ap Rees T. , Khooshemehri P. , Doherty G. , Ong S. , Ivan I. , Goudarzi N. , Gardiner I. , Caine E. , Maguire T. , Leightley D. , Torrico L. , Gasulla A. , Menendez-Vazquez A. , Ortega Prieto Ana Maria , Pickering Suzanne , Guardeño Jose Jimenez , Batra Rahul , Tan A.V.F. , Griffin A. , Papaioannou S. , Trouillet C. , Mischo H. , Giralt V. , Wilson S. , Kirk M. , Neil Stuart , Ribeiro Galao Rui Pedro , Martindale J. , Curtis C. , Zuckerman M. , Razavi R. , Malim M.H. , Martinez-Nunez R.T. 
Published: July 2023

AbstractTesting was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. We performed 158,277 PCRs for our staff, students, and their household contacts, free of charge. Our average turnaround time was 16h and 37 mins from user registration to result delivery. KCL TEST combined open-source automation and in house non-commercial reagents, which allows for rapid deployment. Here we provide our blueprint, recently recommended for ISO15189 accreditation, and results to enable the rapid launch of diagnostic laboratories where and when needed, particularly in low-resource settings. Our data span over 18 months and parallels that of the UK Office for National Statistics, with a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing to decrease outbreaks and provide safe working spaces. Universities can therefore provide agile, resilient, and accurate testing that reflects the infection rate and trend of the general population. We call for the integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test and accommodate efficient low-cost pipelines.
Highly resolved genome assembly and comparative transcriptome profiling reveal genes related to developmental stages of tapewormLigula intestinalis
Authors: Nazarizadeh Masoud , Nováková Milena , Drábková Marie , Catchen Julian , Olson Peter D. , Štefka Jan 
Published: July 2023

AbstractLigula intestinalis(Cestoda: Diphyllobothriidae) is an emerging model organism for studies on parasite population biology and host-parasite interactions. However, a well resolved genome and catalogue of its gene content has not been previously developed. Here, we present the first genome assembly ofL. intestinalis, based on Oxford Nanopore Technologies, Illumina and Omni-C sequencing methodologies. We use transcriptome profiling to compare plerocercoid larvae and adult worms and identify differentially expressed genes associated with these life stages. The genome assembly is 775.5 Mbp in size, with scaffold N50 value of 118 Mbp and encodes 27,256 predicted protein-coding sequences. Over 60% of the genome consists of repetitive sequences. Synteny analyses showed that the 10 largest scaffolds representing 75% of the genome display high correspondence to full chromosomes of cyclophyllidean tapeworms. Mapping RNA-seq data to the new reference genome we identified 3,922 differentially expressed genes in adults compared to plerocercoids. Gene Ontology analyses revealed overrepresented genes involved in reproductive development of the adult stage (e.g. sperm production) and significantly enriched DEGs associated with immune evasion of plerocercoids in their fish host. This study provides the first insights into the molecular biology ofL. intestinalisand provides the most highly contiguous assembly to date of a diphyllobothriid tapeworm useful for population and comparative genomic investigations of parasitic flatworms.
Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions
Authors: Pierre Camille N. , Adams Lily E. , Anasti Kara , Goodman Derrick , Stanfield-Oakley Sherry , Powers John M. , Li Dapeng , Rountree Wes , Wang Yunfei , Edwards Robert J. , Alam S. Munir , Ferrari Guido , Tomaras Georgia D. , Haynes Barton F. , Baric Ralph S. , Saunders Kevin O. 
Published: July 2023

ABSTRACTAntibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of this non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb infusion did not suppress infectious viral titers in the lung as potently as NTD neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Finally, Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection in SARS-CoV-2 infection. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection.AUTHOR SUMMARYCOVID-19 has claimed over 6.8 million lives worldwide and caused economic and social disruption globally. Preventing more deaths from COVID-19 is a principal goal of antibody biologic and vaccine developers. To guide design of such countermeasures, an understanding of how the immune system prevents severe COVID-19 disease is needed. We demonstrate here that antibody functions other than neutralization can contribute to protection from severe disease. Specifically, the functions of antibodies that rely on its Fc portion were shown to confer antibody-mediated protection of mice challenged with a mouse adapted version of SARS-CoV-2. Mice given an antibody that could not neutralize SARS-CoV-2 still showed a decrease in the amount of infectious virus in the lungs and less lung damage than mice given an irrelevant antibody. The decrease in infectious virus in the lungs was even larger when the non-neutralizing antibody was engineered to mediate non-neutralizing effector functions such as antibody-dependent cellular cytotoxicity more potently. Thus, in the absence of neutralization activity, non-neutralizing binding antibodies can contribute to the overall defense against SARS-CoV-2 infection and COVID-19 disease progression.
The p53 Protein is a Suppressor of Atox1 Copper Chaperon in Tumor Cells Under Genotoxic Effects
Authors: Tsymbal Sergey A. , Refeld Alexander G. , Zatsepin Viktor V. , Kuchur Oleg A. 
Published: July 2023

AbstractThe p53 protein is crucial for regulating cell survival and apoptosis in response to DNA damage. However, its influence on therapy effectiveness is controversial: when DNA damage is high p53 directs cells toward apoptosis, while under moderate genotoxic stress it saves the cells from death and promote DNA repair. Furthermore, these processes are influenced by the metabolism of transition metals, particularly copper since they serve as cofactors for critical enzymes. The metallochaperone Atox1 is under intensive study in this context because it serves as transcription factor allegedly mediating described effects of copper. Investigating the interaction between p53 and Atox1 could provide insights into tumor cell survival and potential therapeutic applications in oncology. This study explores the relationship between p53 and Atox1 in HCT116 and A549 cell lines with wild type and knockout TP53. The study found an inverse correlation between Atox1 and p53 at the transcriptional and translational levels in response to genotoxic stress. Atox1 expression decreased with increased p53 activity, while cells with inactive p53 had significantly higher levels of Atox1. Suppression of both genes increased apoptosis, while suppression of the ATOX1 gene prevented apoptosis even under the treatment with chemotherapeutic drugs. The findings suggest that Atox1 may act as one of key elements in promotion of cell cycle under DNA-damaging conditions, while p53 works as an antagonist by inhibiting Atox1. Understanding of this relationship could help identify potential targets in cell signaling pathways to enhance the effectiveness of antitumor therapy, especially in tumors with mutant or inactive p53.
The Vk*MYC Mouse Model recapitulates human multiple myeloma evolution and genomic diversity
Authors: Maura Francesco , Coffey David G. , Stein Caleb K , Braggio Esteban , Ziccheddu Bachisio , Sharik Meaghen E , Du Megan , Alvarado Yuliza Tofaya , Shi Chang-Xin , Zhu Yuan Xiao , Meermeier Erin W. , Morgan Gareth J. , Landgren Ola , Leif Bergsagel P. , Chesi Marta 
Published: July 2023

ABSTRACTDespite advancements in profiling multiple myeloma (MM) and its precursor conditions, there is limited information on mechanisms underlying disease progression. Clincal efforts designed to deconvolute such mechanisms are challenged by the long lead time between monoclonal gammopathy and its transformation to MM. MM mouse models represent an opportunity to overcome this temporal limitation. Here, we profile the genomic landscape of 118 genetically engineered Vk*MYC MM and reveal that it recapitulates the genomic heterogenenity and life history of human MM. We observed recurrent copy number alterations, structural variations, chromothripsis, driver mutations, APOBEC mutational activity, and a progressive decrease in immunoglobulin transcription that inversely correlates with proliferation. Moreover, we identified frequent insertional mutagenesis by endogenous retro-elements as a murine specific mechanism to activate NF-kB and IL6 signaling pathways shared with human MM. Despite the increased genomic complexity associated with progression, advanced tumors remain dependent onMYCexpression, that drives the progression of monoclonal gammopathy to MM.
Benchmarking DNA Isolation Methods for Marine Metagenomics Studies
Authors: Demkina Alina , Slonova Darya , Mamontov Viktor , Konovalova Olga , Yurikova Daria , Rogozhin Vladimir , Belova Vera , Korostin Dmitriy , Sutormin Dmitry , Severinov Konstantin , Isaev Artem 
Published: July 2023

AbstractMetagenomics is a powerful tool to study marine microbial communities. However, obtaining high-quality environmental DNA suitable for downstream sequencing applications is a challenging task. The quality and quantity of isolated DNA heavily depend on the choice of purification procedure and the type of sample. Selection of an appropriate DNA isolation method for a new type of material often entails a lengthy trial and error process. Further, each DNA purification approach introduces biases and thus affects the composition of the studied community. To account for these problems and biases, we systematically investigated efficiency of DNA purification from three types of samples (water, sea sediment, and digestive tract of a model invertebrateMagallana gigas) with eight commercially available microbial DNA isolation kits. For each kit-sample combination we measured the quantity of purified DNA, extent of DNA fragmentation, the presence of PCR-inhibiting contaminants, admixture of eukaryotic DNA, alpha-diversity, and reproducibility of the resulting community composition based on 16S rRNA amplicons sequencing. Additionally, we determined a “kitome”, e.g., a set of contaminating taxa inherent for each type of purification kit used. The resulting matrix of evaluated parameters allows one to select the best DNA purification procedure for a given type of sample.
cloudrnaSPAdes: Isoform assembly using bulk barcoded RNA sequencing data
Authors: Meleshko Dmitry , Prjbelski Andrey D. , Raiko Mikhail , Tomescu Alexandru I. , Tilgner Hagen , Hajirasouliha Iman 
Published: July 2023

AbstractMotivationRecent advancements in long-read RNA sequencing have enabled the examination of full-length isoforms, previously uncaptured by short-read sequencing methods. An alternative powerful method for studying isoforms is through the use of barcoded short-read RNA reads, for which a barcode indicates whether two short-reads arise from the same molecule or not. Such techniques included the 10x Genomics linked-read based SParse Isoform Sequencing (SPIso-seq), as well as Loop-Seq, or Tell-Seq. Some applications, such as novel-isoform discovery, require very high coverage. Obtaining high coverage using long reads can be difficult, making barcoded RNA-seq data a valuable alternative for this task. However, most annotation pipelines are not able to work with a set of short reads instead of a single transcript, also not able to work with coverage gaps within a molecule if any. In order to overcome this challenge, we present an RNA-seq assembler allowing the determination of the expressed isoform per barcode.ResultsIn this paper, we present cloudrnaSPAdes, a tool for assembling full-length isoforms from barcoded RNA-seq linked-read data in a reference-free fashion. Evaluating it on simulated and real human data, we found that cloudrnaSPAdes accurately assembles isoforms, even for genes with high isoform diversity.AvailabilitycloudrnaSPAdes is a feature release of a SPAdes assembler and available athttps://cab.spbu.ru/software/cloudrnaspades/.Contactdmm2017@med.cornell.edu
“You can change your life through sports”: Physical activity interventions to improve the health and wellbeing of adults experiencing homelessness: a mixed methods systematic review
Authors: Dawes Jo , Rogans-Watson Raphael , Broderick Julie 
Published: July 2023

ABSTRACTObjectivesSystematically synthesise evidence of physical activity interventions for people experiencing homelessness (PEH).DesignMixed-methods systematic review.Data sourcesEMBASE, Web of Science, CINAHL, PubMed (MEDLINE), PsycINFO, SPORTDiscus, and Cochrane Library, searched from inception to October 2022.Eligibility CriteriaPICO framework: Population (quantitative and qualitative studies of PEH from high-income countries); Intervention (physical activity, any setting); Comparison (with/ without comparator); Outcome (any health/wellbeing-related outcome).Results3,614 records screened, generating 17 reports [16 studies, 11 qualitative and 5 quantitative (1 RCT, 3 quasi-experimental, 1 analytical cross-sectional)] from UK, USA, Denmark and Australia, including 539 participants (501 PEH, 38 staff). Interventions: soccer (n= 6), group exercise [indoor (n=3), outdoor (n=5)] and individual activities (n=2). Risk of bias assessed using JBI critical appraisal tools. Mixed methods synthesis identified physical and mental health benefits. Qualitative evidence highlighted benefits carried into wider life, challenges participating and positive impact on addiction. Qualitative and quantitative evidence was aligned for the mental health benefits of outdoor exercise and increase in physical activity from indoor group exercise. Quantitative evidence suggested improved bone health and blood lipid markers.ConclusionDiverse interventions were identified with soccer predominating. Qualitative evidence suggested physical activity can benefit health and wellbeing with positive translation to wider daily life. There was some positive quantitative evidence, although most was inconclusive. Evidence suggests a tentative recommendation for physical activity interventions for PEH, however a limitation is that results may not be transferable outside high-income countries. More high-quality research is required to determine effectiveness and optimal programme design.What is already known?People experiencing homelessness suffer a disproportionally higher burden of physical and mental health conditions than housed populations.Regular physical activity can address many health conditions prevalent amongst people experiencing homelessness.What are the new findings?There is evidence of a variety of physical activity interventions that have been designed and provided to engage people experiencing homelessness (for example: soccer, outdoor and indoor group activities, and individual activities).The synthesis of qualitative and quantitative evidence suggests that physical activity can benefit the mental and physical health of people experiencing homelessness with positive translation of benefits to wider life.
Rapid disassembly and Piwi-independent reassembly ofDrosophilapiRNA cluster heterochromatin following acute heat shock
Authors: Rice Nicholas , Ho Samantha , Weng Zhiping , Theurkauf William E. 
Published: July 2023

SummaryEnvironmental stress activates transposons and is proposed to generate genetic diversity that facilitates adaptive evolution. piRNAs guide germline transposon silencing, but the impact of stress on the piRNA pathway is not well understood. InDrosophila,the Rhino-Deadlock-Cuff complex (RDC) drives transcription of clusters composed of nested transposon fragments, generating precursors that are processed into mature piRNAs in the cytoplasm. We show that acute heat shock triggers rapid, reversable, loss of RDC localization and cluster transcript expression with coordinate changes in the cytoplasmic processing machinery. Maternal piRNAs bound to Piwi are proposed to guide Rhino localization to clusters during early embryogenesis. However, RDC re-localization after heat shock is accelerated inpiwimutants and delayed inthoc7mutants, which disrupt piRNA precursor binding to THO complex, and we show that maternally deposited piRNAs are dispensable for RDC localization to the major 42AB cluster. Cluster specification is reconsidered in light of these findings.