bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Inequalities in Mental Health by Family Structure during COVID-19 Lockdowns: Evidence from the UK Household Longitudinal Study
Authors: Green Michael J , Craig Peter , Demou Evangelia , Katikireddi S Vittal , Leyland Alastair H , Pearce Anna 
Published: October 2022

AbstractBackgroundThe COVID-19 pandemic increased psychiatric distress and impacts differed by family structure. We aimed to identify mechanisms contributing to these inequalities.MethodsSurvey data were from the UK Household Longitudinal Study. Psychiatric distress (GHQ-12) was measured in April 2020 (first UK lockdown; n=10,516), and January 2021 (lockdown re-introduced following eased restrictions; n=6,893). Pre-lockdown family structure comprised partner status and presence of children (<16 years). Mediating mechanisms included: active employment, financial strain, childcare/home-schooling, caring, and loneliness. Monte Carlo g-computation simulations were used to adjust for confounding and estimate total effects and decompositions into: controlled direct effects (effects if the mediator was absent), and portions eliminated (PE; representing differential exposure and vulnerability to the mediator).ResultsIn January 2021, after adjustment, we estimated increased risk of distress among couples with children compared to couples with no children (RR: 1.48; 95% CI: 1.15-1.82), largely because of childcare/home-schooling (PE RR: 1.32; 95% CI: 1.00-1.64). Single respondents without children also had increased risk of distress compared to couples with no children (RR: 1.55; 95% CI: 1.27-1.83), and the largest PE was for loneliness (RR: 1.16; 95% CI: 1.05-1.27), though financial strain contributed (RR: 1.05; 95% CI: 0.99-1.12). Single parents demonstrated the highest levels of distress, but confounder adjustment suggested uncertain effects with wide confidence intervals. Findings were similar in April 2020 and when stratified by sex.ConclusionsAccess to childcare/schooling, financial security and social connection are important mechanisms that need addressing to avoid widening mental health inequalities during public health crises.Key MessagesCouples with young children compared to those without, had raised risk of psychiatric distress during UK lockdowns. Effect decompositions suggested this was largely due to a combination of differential exposure and vulnerability to childcare and home-schooling.Among those without young children, being single compared to in a couple was associated with raised risk of psychiatric distress during UK lockdowns, with differential exposure to financial strain and loneliness both contributing to this inequality.There was not sufficient evidence to indicate that being single with young children increased risk of psychiatric distress relative to couples with young children or singles without.
Forecasting Influenza-Like Illness (ILI) during the COVID-19 Pandemic
Authors: Turner Stephen D. , Hulme-Lowe Chris , Nagraj VP 
Published: October 2022

AbstractNear-term probabilistic forecasts for infectious diseases such as COVID-19 and influenza play an important role in public health communication and policymaking. From 2013-2019, the FluSight challenge run by the Centers for Disease Control and Prevention invited researchers to develop and submit forecasts using influenza-like illness (ILI) as a measure of influenza burden. Here we examine how several statistical models and an autoregressive neural network model perform for forecasting ILI during the COVID-19 pandemic, where historical patterns of ILI were highly disrupted. We find that the autoregressive neural network model which forecasted ILI well pre-COVID still performs well for some locations and forecast horizons, but its performance is highly variable, and performs poorly in many cases. We found that a simple exponential smoothing statistical model is in the top half of ranked models we evaluated nearly 75% of the time. Our results suggest that even simple statistical models may perform as well as or better than more complex machine learning models for forecasting ILI during the COVID-19 pandemic. We also created an ensemble model from the limited set of time series forecast models we created here. The limited ensemble model was rarely the best or the worst performing model compared to the rest of the models assessed, confirming previous observations from other infectious disease forecasting efforts on the less variable and generally favorable performance of ensemble forecasts. Our results support previous findings that no single modeling approach outperforms all other models across all locations, time points, and forecast horizons, and that ensemble forecasting consortia such as the COVID-19 Forecast Hub and FluSight continue to serve valuable roles in collecting, aggregating, and ensembling forecasts using fundamentally disparate modeling strategies.
Automated and objective analysis of speech in premanifest and early-stage Huntington’s disease
Authors: Vogel Adam P. , Chan Cheuk S. J. , Stuart Geoffrey W. , Maruff Paul , Lie Yenni , Stout Julie C. 
Published: October 2022

AbstractBackgroundClinical markers that show change in performance in people with Huntington’s disease (HD) during the presymptomatic and prodromal stages remain a target of investigation in clinical medicine. Alongside genetic and neuroimaging initiatives, digital speech analytics has shown promise as a sensitive clinical marker of premanifest HD.ObjectiveTo investigate the sensitivity of digital speech measures for detecting subtle cognitive-linguistic and fine motor features in people carrying the expanded HD gene, with and without symptoms.MethodsSpeech data were acquired from 110 participants (55 people with the expanded HD gene including 16 presymptomatic HD; 16 prodromal HD; 14 early-stage HD; 9 mid-stage HD; and 55 matched healthy controls). Objective digital speech measures were derived from speech tasks that fit along a continuum of motor and cognitive complexity. Acoustic features quantified speakers’ articulatory agility, voice quality and speech-timing. Subjects also completed the tests of cognition and upper limb motor function.ResultsSome presymptomatic HD (furthest from disease onset) differed to healthy controls on timing measures derived from the syllable repetition and monologue. Prodromal HD presented with reduced articulatory agility, reduced speech rate and longer and variable pauses. Speech agility correlated with poorer performance on the upper limb motor test.ConclusionTasks with a mix of cognitive and motor demands differentiated prodromal HD from their matched control groups. Motor speech tasks alone did not differentiate groups until participants were relatively closer to disease onset or symptomatic. Data demonstrated how ubiquitous behaviors like speech, when analyzed objectively, provide insight into disease related change.
The Novel Role of Midbody-Associated mRNAs in Regulating Abscission
Authors: Farmer Trey , Vaeth Katherine F. , Han Ke-Jun , Goering Raeann , Taliaferro J. Matthew , Prekeris Rytis 
Published: October 2022

AbstractMidbodies (MBs) have been shown to function during telophase as a recruiting hub, especially for ESCRT-III complex subunits, to regulate the abscission step of cytokinesis. However, the molecular machinery governing specific protein targeting and activation at the MB remains poorly understood. Until recently, it was thought that abscission regulating proteins, such as ESCRT-III complex subunits, accumulate at the MB by directly or indirectly binding to the MB resident protein, CEP55. However, recent studies have shown that depletion of CEP55 does not fully block ESCRT-III targeting to the MB, and cells in CEP55 knock-out mice divide normally. Additionally, since MBs are microtubule-rich, proteinaceous structures, it is conceptually hard to imagine how large protein complexes, such as the ESCRT-III complex, can successfully diffuse into the MB from the cytosol in a rapid and highly regulated manner. Here, we show that MBs contain mRNAs and that these MB-associated mRNAs can be locally translated, resulting in the accumulation of abscission-regulating proteins. We also demonstrate that localized MB-associated translation of CHMP4B is required for its targeting to the abscission site and that 3′ UTR-dependent CHMP4B mRNA targeting to the MB is required for successful completion of cytokinesis. Finally, we identify regulatorycis-elements within RNAs that are necessary and sufficient for mRNA trafficking to the MB. Based on all this data, we propose a novel method of regulating cytokinesis and abscission by MB-associated targeting and localized translation of selective mRNAs.
Transformer-based deep learning integrates multi-omic data with cancer pathways
Authors: Cai Zhaoxiang , Poulos Rebecca C. , Aref Adel , Robinson Phillip J. , Reddel Roger R. , Zhong Qing 
Published: October 2022

AbstractMulti-omic data analysis incorporating machine learning has the potential to significantly improve cancer diagnosis and prognosis. Traditional machine learning methods are usually limited to omic measurements, omitting existing domain knowledge, such as the biological networks that link molecular entities in various omic data types. Here we develop a Transformer-based explainable deep learning model, DeePathNet, which integrates cancer-specific pathway information into multi-omic data analysis. Using a variety of big datasets, including ProCan-DepMapSanger, CCLE, and TCGA, we demonstrate and validate that DeePathNet outperforms traditional methods for predicting drug response and classifying cancer type and subtype. Combining biomedical knowledge and state-of-the-art deep learning methods, DeePathNet enables biomarker discovery at the pathway level, maximizing the power of data-driven approaches to cancer research. DeePathNet is available on GitHub athttps://github.com/CMRI-ProCan/DeePathNet.HighlightsDeePathNet integrates biological pathways for enhanced cancer analysis.DeePathNet utilizes Transformer-based deep learning for superior accuracy.DeePathNet outperforms existing models in drug response prediction.DeePathNet enables pathway-level biomarker discovery in cancer research.
Bourbon virus transmission, New York State
Authors: Dupuis Alan P. , Prusinski Melissa A. , O’Connor Collin , Maffei Joseph G. , Koetzner Cheri A. , Zembsch Tela E. , Zink Steven D. , White Alexis L. , Santoriello Michael P. , Romano Christopher L. , Xu Guang , Ribbe Fumiko , Campbell Scott R. , Rich Stephen M. , Backenson P. Bryon , Kramer Laura D. , Ciota Alexander T. 
Published: October 2022

AbstractIn July 2019, Bourbon virus RNA was detected in anAmblyomma americanumtick removed from a resident of Long Island, New York. Tick infection and white-tailed deer (Odocoileus virginianus) serosurvey results demonstrate active transmission in New York, especially Suffolk County, emphasizing a need for surveillance anywhereA. americanumis reported.
Extensive Dysregulation of SLK Splicing in Cancers Impacts Metastasis
Authors: Yang Ying-Qun , Hu Yue , Zhang Si-Rui , Li Jie-Fu , Guan Jia-Wen , Zhang Wen-Jing , Sun Yu , Feng Xiao-Yan , Sun Jing , Yang Yun , Wang Zefeng , Wei Huan-Huan 
Published: October 2022

AbstractRNA splicing control is a pivotal aspect of gene regulation and is closely associated with cancer development. From a pan-cancer transcriptome investigation in the splicing layer, we discovered a critical cancer-associated alternative splicing (AS) event at exon 13 of SLK which produces two isoforms, SLK-L and SLK-S. The splicing is dramatically shifted towards SLK-L across multiple prevalent cancer types. We demonstrated that SLK-L plays an essential role in cancer development, especially in metastasis both in cells and in mice, whereas splicing toward SLK-S inhibits cancer development. RNA-seq revealed the two SLK isoforms play different roles in pathways related to cell migration. Furthermore, different SLK isoforms demonstrate varying binding affinities to certain cell junction markers, in part indicating the AS of SLK contributes to cancer cell migration. In addition, the splicing factor Rbfox2 was identified to specifically inhibit the inclusion of exon 13 by binding intron 12 of SLK. Collectively, our study innovatively uncovers the biological consequences and underlying mechanisms for one of the most mis-spliced genes in cancer, highlighting its potential significance in cancer diagnosis and treatment.
Ubiquitination steers SRF3 plasma membrane nano-organization to specify signaling outputs
Authors: Pierre Platre Matthieu , Matias Gleason Flores , Lukas Brent , Min Cao , Ling Zhang , Satbhai Santosh B. , Julie Neveu , Gregory Vert , Wolfgang Busch 
Published: October 2022

ABSTRACTOrganisms cope with myriads of competing and conflicting environmental signals. These signals are often perceived by cell surface receptor kinases to mount appropriate adaptive responses. However, it is not well understood by which mechanism single receptor kinases can transduce different signals. The plant receptor kinase SRF3 transduces low iron and bacteria-derived signals. We found that upon these signals, ubiquitinated SRF3 is recognized by clathrin-mediated endocytosis for vacuolar targeting. Live super resolution microscopy revealed that cell surface SRF3 is present in a fast diffusible fraction, which is sustained by ubiquitination, and that non-ubiquitinated SRF3 is present in immobile nanodomains. Ubiquitination-mediated degradation of SRF3 is required for signaling only under low iron but not upon flg22 perception. Flg22-triggered SRF3 phosphorylation leads to SRF3 accumulation in the immobile fraction in which degradation is restricted, thereby preventing low iron signaling. We therefore propose that ubiquitination-dependent plasma membrane nano-organization of SRF3 specifies its signal transduction pathways.
Protection against reinfection with SARS-CoV-2 omicron BA.2.75*sublineage
Authors: Chemaitelly Hiam , Tang Patrick , Coyle Peter , Yassine Hadi M. , Al-Khatib Hebah A. , Smatti Maria K. , Hasan Mohammad R. , Ayoub Houssein H. , Altarawneh Heba N. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar H. , Latif Ali N. , Shaik Riyazuddin M. , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed G. , Butt Adeel A. , Al-Romaihi Hamad E. , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J. 
Published: October 2022

Abstract
An energy-saving glasshouse film reduces seasonal, and cultivar dependent Capsicum yield due to light limited photosynthesis
Authors: Chavan Sachin G. , He Xin , Maier Chelsea , Alagoz Yagiz , Anwar Sidra , Chen Zhong-Hua , Ghannoum Oula , Cazzonelli Christopher I. , Tissue David T. 
Published: October 2022

AbstractGlasshouse films can be used to reduce energy costs by limiting non-productive heat-generating radiation, but the impact on yield of greenhouse horticultural crops remains unknown. The effects of energy-saving film ULR-80 (referred to as Smart Glass; SG) designed to block long wavelength light that generates heat also reduced photosynthetically active radiation (PAR) consequently affecting crop morphology, photosynthesis, leaf pigments, and yield of two hydroponically grown capsicum (Capsicum annuumL.) cultivars (Red and Orange). The crops were grown in four high-tech glasshouse bays over two seasons of similar daily light integrals (DLI) during ascending (Autumn) and descending (Summer) photoperiods. The Red cultivar exhibited higher photosynthetic rates (light saturated -Asatand maximal -Amax) and yield than the Orange cultivar in control but displayed stronger reductions in modelled photosynthetic rates at growth light and yield in SG without changes in photosynthetic capacity. Foliar pigment ratios of chlorophyll a/b and carotenoid: chlorophyll remained unaffected by the SG during both seasons indicating that chloroplast homeostasis was similar between SG and control. The seasonal differences in photosynthetic pigments and xanthophyll de-epoxidation state (DPS) revealed that cultivars were able to sense the SG-altered light environment during the ascending, but not descending photoperiod. The descending photoperiod correlated with a lower daily light level and a substantial yield reduction of 29 % and 13 % in Red and Orange cultivars, respectively. Thus, SG-induced higher reductions in yield during the descending photoperiod indicate that SG may be more beneficial for capsicum crops planted during Autumn with an ascending photoperiod.HighlightsA potential energy saving SG film limited net photosynthesis of capsicumThe SG film reduced yield of two capsicum cultivars that can be mitigated by planting during the low light growth season with a shorter photoperiodSG reduced genotype-dependent capsicum yield was associated with alterations in the level of foliar pigments required for photoprotection under adverse light conditions
Expression of terminal deoxynucleotidyl transferase (TdT) identifies lymphoid-primed progenitors in human bone marrow
Authors: Kim YeEun , Calderon Ariel A. , Favaro Patricia , Glass David R. , Tsai Albert G. , Borges Luciene , Greenleaf William J. , Bendall Sean C. 
Published: October 2022

AbstractLymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conducted a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identified terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincided with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions showed enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs was inversely related to the SLAM family member CD84. Prospective isolation of CD84loGMPs demonstrated robust lymphoid potentialex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies previously unappreciated lymphoid-primed progenitors, redefining the lympho-myeloid axis in human hematopoiesis.
Virulence factors among isolates of extraintestinalEscherichia coli(ExPEC) from hospitals in the United Kingdom
Authors: Turton Jane F 
Published: October 2022

Abstract182 genes associated with virulence were sought from the whole genome sequences of all non-duplicate isolates ofEscherichia colireceived by the UK Health Security Agency’s Antimicrobial Resistance and HealthCare Associated Infections laboratory for typing between June 2019 and March 2021 from hospitals in the United Kingdom and Republic of Ireland (n=593). These were from healthcare associated investigations and were not associated with diarrhoeal disease. Genes that were very common or very rare were excluded from further analysis. The frequency of detection of genes was compared among isolates from invasive infection, screening, urine samples and from neonates.cnf1(coding for cytotoxic necrotising factor),clbK(coding for colibactin),focCDF(coding for F1 fimbriae),kpsM_K1,neuBD(associated with the K1 capsule),mchBC,mcmA(coding for microcins),papG_alleleIII (part of a cluster encoding P fimbriae),pic(protein involved in intestinal colonization),sfaE/sfafoCDE(coding for S fimbriae),tcpC(encoding TLR domain containing-protein C) andvat(encoding toxin vacuolating autotransporter) were 4 to 28 times more prevalent among isolates from invasive infections than among those from carriage. Representatives of sequence types (ST) 12, 73, 998 and 127 carried multiple of these virulence factors, no matter whether they were from screening swabs or from blood or other infection sites. Isolates carrying multiple virulence factors were more prevalent from neonatal screens than those from general screens. Genes associated with the K1 capsule (ibeA,neuBD,kpsM_K1) were particularly found in STs 1193, 10, 998, 538, 80 and 141. Nanopore sequencing of 14 isolates representing 10 different STs showed that the virulence elements sought were largely carried in chromosomal genomic islands, which were mosaic in nature. Some 9 % of isolates carried more than six of the main virulence genes/gene sets sought, highlighting the potential for significant numbers of carriage isolates to cause extraintestinal infections.
LSR Targets YAP to Modulate Intestinal Paneth Cell Differentiation
Authors: An Yanan , Wang Chao , Fan Baozhen , Li Ying , Kong Feng , Zhou Chengjun , Cao Zhang , Liu Jieying , Wang Mingxia , Sun Hui , Zhao Shengtian , Gong Yongfeng 
Published: October 2022

SUMMARYLipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that is best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis and pathogenesis of intestinal disease. By using multiple conditional deletion mouse models andex vivocultured organoids, we find that LSR elimination in intestinal stem cells results in disappearance of Paneth cell without affecting the differentiation of other cell lineages. Mechanistic studies reveal that LSR deficiency increases abundance and nuclear localization of YAP by modulating its phosphorylation and proteasomal degradation. Using gain- and loss-of-function studies we show that LSR protects against necrotizing enterocolitis through enhancement of Paneth cell differentiation in small intestinal epithelium. Thus, this study identifies LSR as an upstream negative regulator of YAP activity, an essential factor for Paneth cell differentiation, and a potential novel therapeutic target for inflammatory bowel disease.
Striatal neurons are recruited dynamically into collective representations of self-initiated and learned actions in freely-moving mice
Authors: Tiroshi Lior , Atamna Yara , Gilin Naomi , Goldberg Joshua A. 
Published: October 2022

SummaryStriatal spiny projection neurons are hyperpolarized-at-rest (HaR) and are driven to spike threshold by a small number of powerful inputs – an input-output configuration that is detrimental to response reliability. Because the striatum is important for habitual behaviors and goal-directed learning, we conducted microendoscopic imaging in freely-moving mice that express a genetically-encoded calcium indicator sparsely in striatal HaR neurons to compare their response reliability during self-initiated movements and operant conditioning. The sparse expression was critical for longitudinal studies of response reliability, and for studying correlations among HaR neurons while minimizing spurious correlations arising from contamination by the background neuropil signal. We found that HaR neurons are recruited dynamically into action representation through a moment-by-moment formation of distinct cell assemblies. While individual neurons respond with little reliability, the population response remained reliable. Moreover, we found evidence for the formation of correlated cell assemblies during conditioned (but not innate) behaviors, but this correlation was independent of the distance between neurons.