bluuebunny/crossref_metadata_2025_split huggingface dataset:
New phenotype discovery method by unsupervised deep representation learning empowers genetic association studies of brain imaging
Authors: Patel Khush , Xie Ziqian , Yuan Hao , Islam Sheikh Muhammad Saiful , Zhang Wanheng , Gottlieb Assaf , Chen Han , Giancardo Luca , Knaack Alexander , Fletcher Evan , Fornage Myriam , Ji Shuiwang , Zhi Degui 
Published: December 2022

AbstractUnderstanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6,130 UK Biobank (UKBB) participants’ T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as endophenotypes (ENDOs). GWAS of these ENDOs in held-out UKBB subjects (n = 22,962 discovery and n = 12,848/11,717 replication cohorts for T1/T2) identified 658 significant replicated variant-ENDO pairs involving 43 independent loci. Thirteen loci were not reported in earlier T1 and T2 IDP-based UK Biobank GWAS. We developed a perturbation-based decoder interpretation approach to show that these loci are associated with ENDOs mapped to multiple relevant brain regions. Our results established unsupervised deep learning can derive robust, unbiased, heritable, and interpretable endophenotypes from imaging data.
RNA-Chrom: a manually-curated analytical database of RNA–chromatin interactome
Authors: Ryabykh G. K. , Kuznetsov S. V. , Korostelev Y. D , Sigorskikh A. I. , Zharikova A. A. , Mironov A. A. 
Published: December 2022

AbstractEvery year there is more and more evidence that non-coding RNAs play an important role in biological processes affecting various levels of organisation of living systems: from the cellular (regulation of gene expression, remodeling and maintenance of chromatin structure, co-transcriptional suppression of transposons, splicing, post-transcriptional RNA modifications, etc.), to cell populations and even organismal ones (development, aging, cancer, cardiovascular and many other diseases). The development and creation of mutually complementary databases that will aggregate, unify and structure different types of data can help to reach the system-level of studying non-coding RNAs. Here we present the RNA-Chrom manually-curated analytical database, which contains the coordinates of billions of contacts of thousands of human and mouse RNAs with chromatin. Through the user-friendly web interface (https://rnachrom2.bioinf.fbb.msu.ru/), two approaches to the analysis of the RNA–chromatin interactome were implemented. Firstly, to find out whether the RNA of interest to a user contacts with chromatin, and if so, with which genes or DNA loci? Secondly, to find out which RNAs are in contact with the DNA locus of interest to a user (and probably participate in its regulation), and if there are such, what is the nature of their interaction? For a more detailed study of contact maps and their comparison with other data, the web interface allows a user to view them in the UCSC Genome Browser.
Chronomodulated administration of chemotherapy in advanced colorectal cancer. A systematic review and meta-analysis
Authors: Nassar Ahmed , Abdelhamid Amir , Ramsay George , Bekheit Mohamed 
Published: December 2022

AbstractAimIn this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as delivery of chemotherapy timed according to the human circadian rhythm, were assessed, and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer.MethodsElectronic English-language studies published until October 2020 were searched. Randomised Controlled Trials (RCTs) compared chronomodulated chemotherapy with non-chronomodulated (Conventional) chemotherapy for management of advanced colorectal cancer were included. Main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic database search in Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review (CDSR).ResultsIn total, 7 RCTs including 1137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range: 47.2 - 64) years.There is no significant difference between chronomodulated and conventional chemotherapy in ORR ((risk ratio (RR) 1.15; 95%CI [0.87-1.53]). There was no significant difference in gastrointestinal toxicity under the random effect model RR 1.02; CI 95% [0.68 – 1.51]. No significant difference was found regarding neurological and skin toxicities, (RR 0.64,95%CI [0.32 – 1.27]) and (RR 2.11, 95%CI [0.33-13.32]), respectively. However, patients who received chronomodulated chemotherapy had fewer haematological toxicity, (RR 0.36, 95%CI [0.27-0.48]).ConclusionThere was no overall difference in ORR or toxicity but haematologic, between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy could be considered in patients at high risk of haematological toxicities.
Frailty increases the risk of adverse outcomes among 38,950 UK Biobank participants with prediabetes: A prospective cohort study
Authors: Cao Xingqi , Li Xueqin , Zhang Jingyun , Sun Xiaoyi , Yang Gan , Zhao Yining , Li Shujuan , Hoogendijk Emiel O. , Wang Xiaofeng , Zhu Yimin , Allore Heather , Gill Thomas M. , Liu Zuyun 
Published: December 2022

AbstractBackgroundWe aimed to systematically evaluate the associations of frailty, a simple health indicator, with risks of multiple adverse outcomes in late life among adults with prediabetes.MethodsWe evaluated 38,950 adults aged 40-64 years with prediabetes from the baseline survey of the UK Biobank. Frailty was assessed using the frailty phenotype (FP, 0-5), and participants were grouped into non-frail (FP =0), pre-frail (1≤ FP ≤2), and frail (FP ≥3). Multiple health outcomes were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations.ResultsAt baseline, 49.1% and 5.9% of adults with prediabetes were identified as pre-frail and frail, respectively. Both pre-frailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <0.001). For instance, compared with their non-frail counterparts, frail participants with prediabetes had a significantly higher risk (P <0.001) of type 2 diabetes mellitus (T2DM) (hazard ratio [HR]: 1.73), diabetes-related microvascular disease (HR: 1.89), cardiovascular disease (HR: 1.66), chronic kidney disease (HR: 1.76), eye disease (HR: 1.31), dementia (HR: 2.03), depression (HR: 3.01), and all-cause mortality (HR: 1.81) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%.ConclusionsIn UK adults with prediabetes, both pre-frailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into the routine care for middle-aged adults with prediabetes, to improve the allocation of healthcare resources and reduce diabetes-related burdens.
Lateral diffusion of NKCC1 contributes to neuronal chloride homeostasis and is rapidly regulated by the WNK signaling pathway
Authors: Côme Etienne , Blachier Simon , Gouhier Juliette , Russeau Marion , Lévi Sabine 
Published: December 2022

AbstractAn upregulation of the Na+-K+-2Cl-co-transporter NKCC1, the main chloride importer in mature neurons, can lead to depolarizing/excitatory responses mediated by GABAAreceptors and thus to hyperactivity. Understanding the regulatory mechanisms of NKCC1 would help prevent intra-neuronal chloride accumulation that occurs in pathologies with defective inhibition. The cellular and molecular regulatory mechanisms of NKCC1 are poorly understood. Here, we report in mature hippocampal neurons that GABAergic activity controls the membrane diffusion and clustering of NKCC1 via the chloride-sensitive WNK1 kinase and the downstream SPAK kinase that directly phosphorylates NKCC1 on key threonine residues. At rest, this signaling pathway has little effect on intracellular Cl-concentration but it participates to the elevation of intraneuronal Cl-concentration in hyperactivity condition associated with an up-regulation of NKCC1. The fact that the chloride exporter KCC2 is also regulated in mature neurons by the WNK1 pathway indicates that this pathway will be a target of choice in the pathology.
Non-Local Conceptual Combination
Authors: Parrish Alicia , Rodriguez Amilleah , Pylkkänen Liina 
Published: December 2022

ABSTRACTIt is uncontroversial that the syntax of an expression largely determines its meaning. For example, there is no way to interpret a sentence like “the blue hat has a white bow” as telling you that there is a white hat that has blue bow. But to what extent are the brain’s combinatory interpretive routines exclusively locked into the structures given by syntax? Consider another example: “The blue color of his hat is pretty.” This sentence tells us that a color is pretty, that the color is blue and that the color belongs to a hat. What the syntax of this sentence does not give us is a combination of “blue” and “hat.” But clearly, if we were to draw a picture of the meaning of this sentence, it would have a blue hat in it. We asked: upon encountering “hat” in this sentence, do our brains combine the features of “blue” with the features of “hat,” despite the long distance between them and no direct syntactic relation? By using a known neural measure of conceptual combination in the left anterior temporal lobe, we obtained evidence using MEG that our brains appear to perform such a long-distance conceptual combination that does not track the syntax. Intriguingly, word (or rather concept) order affected the directionality of the effect. While the effect of concept order remains a topic for future work, our results overall suggest that the meaning composition system of language is likely richer than the combinatory steps predicted from syntactic structures.
3D Graph Contrastive Learning for Molecular Property Prediction
Authors: Moon Kisung , Im Hyeon-Jin , Kwon Sunyoung 
Published: December 2022

AbstractMotivationSelf-supervised learning (SSL) is a method that learns the data representation by utilizing supervision inherent in the data. This learning method is in the spotlight in the drug field, lacking annotated data due to time-consuming and expensive experiments. SSL using enormous unlabeled data has shown excellent performance for molecular property prediction, but a few issues exist. (1) Existing SSL models are large-scale; there is a limitation to implementing SSL where the computing resource is insufficient. (2) In most cases, they do not utilize 3D structural information for molecular representation learning. The activity of a drug is closely related to the structure of the drug molecule. Nevertheless, most current models do not use 3D information or use it partially. (3) Previous models that apply contrastive learning to molecules use the augmentation of permuting atoms and bonds. Therefore, molecules having different characteristics can be in the same positive samples. We propose a novel contrastive learning framework, small-scale 3D Graph Contrastive Learning (3DGCL) for molecular property prediction, to solve the above problems.Results3DGCL learns the molecular representation by reflecting the molecule’s structure through the pre-training process that does not change the semantics of the drug. Using only 1,128 samples for pre-train data and 0.5 million model parameters, we achieved state-of-the-art or comparable performance in six benchmark datasets. Extensive experiments demonstrate that 3D structural information based on chemical knowledge is essential to molecular representation learning for property prediction.AvailabilityData and codes are available inhttps://github.com/moonkisung/3DGCL.Contactsy.kwon@pusan.ac.kr
Heat wave, COVID-19, and mortality excess in the 2022 summer: a cohort study on data from Italian surveillances
Authors: Venturelli Francesco , Mancuso Pamela , Vicentini Massimo , Ottone Marta , Storchi Cinzia , Roncaglia Francesca , Bisaccia Eufemia , Ferrarini Chiara , Pezzotti Patrizio , Rossi Paolo Giorgi 
Published: December 2022

AbstractWe aimed to assess differences in the summer excess of mortality by COVID-19 history using data from the mortality and COVID-19 surveillances. We found 4% excess risk in 2022 summer, compared to 2015-2019. A mortality rate ratio of 1.59 (95%CI 1.39-1.82) for COVID-19 survivors compared to naïve, was found. Both were higher in people aged ≥75 years. During the July heat wave, the excess for COVID-19 survivors decreased and disappeared when excluding people living in nursing homes.Funding statementThis study was partially supported by the Italian Ministry of Health –CCM 2020 - “Sorveglianza epidemiologica e controllo del COVID-19 in aree urbane metropolitane e per il contenimento della circolazione del Sars-CoV-2 nella popolazione immigrata in Italia” and by the Ricerca Corrente 2023Highlightsthe excess of mortality in COVID-19 survivors is not exacerbated by heatwavesan excess of mortality during the whole summer in COVID-19 survivors aged over 75 suggest that no harvesting effect is appreciable in the older population that survived COVID-19For COVID-19 survivors aged over 75, a lower mortality than the naïve population was observed only during the July heat wave when we stratified by residency
Comparable in vivo joint kinematics between self-reported stable and unstable knees after TKA can be explained by muscular adaptation strategies: a retrospective observational study
Authors: Rao Longfeng , Horn Nils , Meister Nadja , Preiss Stefan , Taylor William R. , Santuz Alessandro , Schütz Pascal 
Published: December 2022

AbstractBackgroundPostoperative knee instability is one of the major reasons accounting for unsatisfactory outcomes, as well as a major failure mechanism leading to total knee arthroplasty (TKA) revision. Nevertheless, subjective knee instability is not well defined clinically, plausibly because the relationships between instability and implant kinematics during functional activities of daily living remain unclear. Although muscles play a critical role in supporting the dynamic stability of the knee joint, the influence of joint instability on muscle synergy patterns is poorly understood. Therefore, this study aimed to understand the impact of self-reported joint instability on tibiofemoral kinematics and muscle synergy patterns after TKA during functional gait activities of daily living.MethodsTibiofemoral kinematics and muscle synergy patterns were examined during level walking, downhill walking, and stair descent in eight self-reported unstable knees after TKA (3M:5F, 68.9±8.3 years, BMI 26.1±3.2 kg/m2, 31.9±20.4 months postoperatively), and compared against ten stable TKA knees (7M:3F, 62.6±6.8 years, 33.9±8.5 months postoperatively, BMI 29.4±4.8 kg/m2). For each knee joint, clinical assessments of postoperative outcome were performed, while joint kinematics were evaluated using moving video-fluoroscopy, and muscle synergy patterns were recorded using electromyography.ResultsOur results reveal that average condylar A-P translations, rotations, as well as their ranges of motion were comparable between stable and unstable groups. However, the unstable group exhibited more heterogeneous muscle synergy patterns and prolonged activation of knee flexors compared to the stable group. In addition, subjects who reported instability events during measurement showed distinct, subject-specific tibiofemoral kinematic patterns in the early/mid-swing phase of gait.ConclusionsOur findings suggest that accurate movement analysis is sensitive for detecting acute instability events, but might be less robust in identifying general joint instability. Conversely, muscle synergy patterns seem to be able to identify muscular adaptation associated with underlying chronic knee instability.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Estimating Subnational Excess Mortality in Times of Pandemic. An application to Frenchdépartementsin 2020
Authors: Bonnet Florian , Camarda Carlo Giovanni 
Published: December 2022

AbstractThe Covid-19 pandemic did not affect sub-national regions in a uniform way. Knowledge of the impact of the pandemic on mortality at the local level is therefore an important issue for better assessing its burden. Vital statistics are now available for an increasing number of countries for 2020 and 2021, and allow the calculation of sub-national excess mortality. However, this calculation faces two important methodological challenges: (1) it requires appropriate mortality projection models; (2) small populations implies important uncertainty in the estimates, commonly neglected. We address both issues by adopting a method to forecast mortality at sub-national level and by incorporating uncertainty in the computation of mortality measures. We illustrate our approach to Frenchdépartements(NUTS 3, 95 geographical units) and produce estimates for 2020 and both sexes. Nonetheless, the proposed approach is so flexibility to allow estimation of excess mortality during Covid-19 in most demographic scenarios as well as for past pandemics.
Neurogenetic Mechanisms of Risk for ADHD: Examining Associations of Functionally-Annotated Polygenic Scores and Brain Volumes in a Population Cohort
Authors: He Quanfa , Keding Taylor , Zhang Qi , Miao Jiacheng , Herringa Ryan J. , Lu Qiongshi , Travers Brittany G. , Li James J. 
Published: December 2022

AbstractBackgroundADHD polygenic scores (PGS) are reliably predictive of ADHD outcomes across studies. However, traditional PGS arestatisticalindices of genetic liability – predictive of ADHD but uninformed bybiologicalinformation. The objective of our study was to determine whether a novel, biologically-informed, functionally annotated ADHD PGS can reveal specific brain mechanisms of risk for ADHD.MethodsData were from the Philadelphia Neurodevelopmental Cohort (n=555). Multiple mediation models were tested to examine the indirect effects of ADHD PGS (including one using a functionally annotated approach, i.e.,AnnoPred) on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Age-stratified analyses (children, adolescents, and young adults) were also conducted to account for developmental differences.ResultsA direct effect was detected betweenAnnoPredPGS and IA symptoms in adolescents only. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, ADHD PGS were consistently associated with the DLPFC.ConclusionsA biologically-informed PGS yielded a more powerful (and developmentally-specific) signal in detecting a direct effect of ADHD PGS on adolescent IA symptoms. However, no indirect effects between ADHD PGS and ADHD symptomology via the brain emerged. ADHD will become increasing predictive as discovery sample sizes climb. Studies that integrate both genetic and neuroimaging information are critical to advancing our understanding of the biological mechanisms underlying ADHD.
Sporting tournaments and changed birth rates 9 months later: a systematic review
Authors: Masukume Gwinyai , Grech Victor , Ryan Margaret 
Published: December 2022

AbstractIntroductionEmerging evidence suggests that major sporting tournaments are associated with increased birth rates 9 months afterwards. This increase has been attributed to the celebratory atmosphere encouraging more conception through increased sexual activity among the populace.MethodsStudies that examined the relationship between a major sporting tournament and altered birth metrics (number of births and/or birth sex ratio, defined as male divided by total live births) 9(±1) months later were sought out systematically through searches of PubMed and Scopus. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in conducting this study.ResultsFive major sporting tournaments were linked to noticeably increased birth metrics 9(±1) months later. The Super Bowl (increased United States birth sex ratio in multiple years, however, from 2004 to 2013 there were no observable birth increases in winning counties and losing was not associated with a changed number of births), the 2009 UEFA Champions League (16% increase in Solsonès and Bages births in Spain), the 2010 FIFA World Cup (increased birth sex ratio and over 1000 extra births in South Africa), the 2016 UEFA Euros (2% increase in Northern Ireland births) and the 2019 Rugby World Cup (increased birth sex ratio in some Japanese prefectures). Nine months after the most popular provincialla Ligasoccer teams unexpectedly lost matches, there were 0.8% fewer births in those provinces from 2001 to 2015; the number of births were unaffected by unexpected wins. After the 1998 FIFA World Cup a changed sex ratio at birth was not witnessed 9 months on. Nine months following a performance improvement of one standard deviation by a European national soccer team at the FIFA World Cup or UEFA Euro Championships, from 1960 to 2016, there was a 0.3% decline in births 9 months on.ConclusionsWith a few exceptions, major American football, Association football (soccer) and Rugby apex tournaments in Africa, North America, Asia and Europe were associated with increases in the number of babies born and/or in the birth sex ratio 9(±1) months following notable team wins and/or hosting the tournament. Related to this, unexpected losses by teams from a premier soccer league were associated with a decline in births 9 months on. In conclusion, Nelson Mandela was correct when he averred, “Sport has the power to change the world. It has the power to inspire, it has the power to unite people in a way that little else does.”PROSPERO registrationCRD42022382971