bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environment-wide and epigenome-wide association study of adiposity in “Children of 1997” birth cohort
Authors: Zhao Jie V , Fan Bohan , Huang Jian , Cowling BJ , Au Yeung SL , Baccarelli Andrea , Leung GM , Schooling C Mary 
Published: September 2022

AbstractBackgroundIncreasing childhood adiposity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of adiposity at the onset and end of puberty in Hong Kong the most economically developed major Chinese city.MethodsWe conducted an environment-wide association study (EWAS) and an epigenome-wide association study of adiposity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kong’s population-representative “Children of 1997” birth cohort. Univariable linear regression was used to select exposures related to adiposity at ~11.5 years (BMI n≤7,119, WHR n=5,691) and ~17.6 years (n = 3,618) at Bonferroni-corrected significance, and multivariable linear regression to adjust for potential confounders followed by replication (n=308) and CpG by CpG analysis (n=286) at ~23 years. Findings were compared with evidence from randomized controlled trials (RCTs) and Mendelian randomization (MR) studies.ResultsAt ~11.5 and ~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as seven and 12 associated with WHR respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with adiposity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, binge eating, and possibly earlier puberty are consistent with available evidence from RCTs or MR studies We found 21 CpGs related to BMI and 18 to WHR.ConclusionsThese novel insights into potentially modifiable factors associated with adiposity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings.FundingThis study was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction was supported by CFS-HKU1.
A Systems Biology Approach to Pathogenesis of Gastric Cancer: Gene Network Modeling and Pathway Analysis
Authors: Mottaghi-Dastjerdi Negar , Ghorbani Abozar , Montazeri Hamed 
Published: September 2022

AbstractIntroductionGastric cancer (GC) ranks among the most common malignancies worldwide. In our previous study, we found overexpressed genes in GC clinical samples. The goal of the current study was to find critical genes and key pathways involved in the pathogenesis of GC.MethodsGene interactions were analyzed using STRING, and Cytoscape was used to visualize the molecular interaction network. CytoHubba was used for drawing the PPI network and identifying hub proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) at STRING were used for the enrichment analysis of the hub genes. Cluster analysis of the network was done using CytoCluster. MEME Suite was used for promoter analysis of the hub genes using Tomtom and GoMo tools.Results and DiscussionOur results showed that the most affected processes in GC are the metabolic processes. The OXPHOS pathway was also considerably enriched in our analyses. These results showed the significant role of mitochondria in GC pathogenesis. Although many investigations have focused on the mitochondrial role in the pathogenesis of various cancers, the characteristics of respiratory and metabolic changes in GC have not been fully elucidated. Our results also showed that most of the affected pathways in GC were the pathways also involved in neurodegenerative diseases. Also, promoter analysis showed that negative regulation of signal transduction might play an important role in GC pathogenesis. The results of this study might open up new insights into GC pathogenesis. The identified genes might be novel diagnostic or prognostic biomarkers or potential therapeutic targets for GC. Nonetheless, these results were obtained by bioinformatics analysis and require further clinical validation.
Multiscale compression-induced restructuring of stacked lipid bilayers: from buckling delamination to molecular packing
Authors: Porras-Gómez Marilyn , Kim Hyunchul , Dronadula Mohan Teja , Kambar Nurila , Metellus Christopher J.B. , Aluru Narayana R. , van der Zande Arend , Leal Cecília 
Published: September 2022

AbstractLipid membranes in nature adapt and reconfigure to changes in composition, temperature, humidity, and mechanics. For instance, the oscillating mechanical forces on lung cells and alveoli influence membrane synthesis and structure during breathing. However, despite advances in the understanding of lipid membrane phase behavior and mechanics of tissue, there is a critical knowledge gap regarding the response of lipid membranes to micromechanical forces. Most studies of lipid membrane mechanics use supported lipid bilayer systems missing the structural complexity of pulmonary lipids in alveolar membranes comprising multi-bilayer interconnected stacks. Here, we elucidate the collective response of the major component of pulmonary lipids to strain in the form of multi-bilayer stacks supported on flexible elastomer substrates. We utilize X-ray diffraction, scanning probe microscopy, confocal microscopy, and molecular dynamics simulation to show that lipid multilayered films both in gel and fluid states evolve structurally and mechanically in response to compression at multiple length scales. Specifically, compression leads to increased disorder of lipid alkyl chains comparable to the effect of cholesterol on gel phases as a direct result of the formation of nanoscale undulations in the lipid multilayers, also inducing buckling delamination and enhancing multi-bilayer alignment. We propose this cooperative short- and long-range reconfiguration of lipid multilayered films under compression constitutes a mechanism to accommodate stress and substrate topography. Our work raises fundamental insights regarding the adaptability of complex lipid membranes to mechanical stimuli. This is critical to several technologies requiring mechanically reconfigurable surfaces such as the development of electronic devices interfacing biological materials.
Dispensing with unnecessary assumptions in population genetics analysis
Authors: Labayle Pabet Olivier , Tetley-Campbell Kelsey , van der Laan Mark J. , Ponting Chris P. , Beentjes Sjoerd Viktor , Khamseh Ava 
Published: September 2022

AbstractParametric assumptions in population genetics analysis – including linearity, sources of population stratification and additivity of variance as part of a Gaussian noise – are often made, yet their (approximate) validity depends on variant and traits of interest, as well as genetic ancestry and population dependence structure of the sample cohort. We present a unified statistical workflow, called TarGene, for targeted estimation of effect sizes, as well as two-point and higher-order epistatic interactions of genomic variants on polygenic traits, which dispenses with these unnecessary assumptions. Our approach is founded on Targeted Learning, a framework for estimation that integrates mathematical statistics, machine learning and causal inference. TarGene maximises power whilst simultaneously maximising control over false discoveries by: (i) guaranteeing optimal bias-variance trade-off, (ii) taking into account potential covariate non-linearities, sources of population stratification and dependence structure, and (iii) detecting genetic non-linearities. The necessity of this model-independent approach is demonstrated via extensive simulations. We validate the effectiveness of our method by reproducing previously verified effect sizes on UK Biobank data, whilst simultaneously discovering non-linear effect sizes of additional allelic copies on trait or disease, in a PheWAS study involving 781 traits. Specifically, we demonstrate genetic non-linearity at the FTO locus is significant for 54 traits in this study. We further find three pairs of epistatic loci associated with skin color that have been previously reported to be associated with hair color. Finally, we illustrate how TarGene can be used to investigate higher-order interactions using three variants linked to the vitamin D receptor complex. TarGene provides a platform for comparative analyses across biobanks, or integration of multiple biobanks and heterogeneous populations to simultaneously increase power and control for type I errors, whilst taking into account population stratification and complex dependence structures.
Mathematical reconstruction of the metabolic network in anin-vitromultiple myeloma model
Authors: Vera-Siguenza Elias , Escribano-Gonzalez Cristina , Serrano-Gonzalo Irene , Eskla Kattri-Liis , Spill Fabian , Tennant Daniel 
Published: September 2022

AbstractIt is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies that exclusively utilisein-vitromono-culture models could prove to be limited for uncovering novel metabolic targets that can translate into clinical therapies. Although this is increasingly recognised, and work addressing this is becoming routinary in a rapidly emerging field, much remains unknown.This study employs an interdisciplinary approach that leverages the predictive power of mathematical modelling to enrich experimental findings. We develop a functional multicellularin-silicomodel that facilitates the qualitative and quantitative analysis of the metabolic network spawned by anin-vitroco-culture model of bone marrow mesenchymal stem- and myeloma cell lines. To procure this model, we devised a bespoke human genome constraint-based reconstruction workflow that combines aspects from the legacy mCADRE & Metabotools algorithms, the novel redHuman algorithm, along with13C-metabolic flux analysis. Our workflow transforms the latest human metabolic network matrix (Recon3D) into two cell-specific models coupled with a metabolic network spanning a shared growth medium. When cross-validating ourin-silicomodel against the in-vitro model, we found that thein-silicomodel successfully reproduces vital metabolic behaviours of itsin-vitrocounterpart; results include cell growth predictions, respiration rates, as well as support for observations which suggest cross-shuttling of redox-active metabolites between cells. Together, our methodology and its results provide yet another step toward the relevance of studies of this type in the field.
Histone chaperone ASF1 mediates H3.3-H4 deposition in Arabidopsis
Authors: Zhong Zhenhui , Wang Yafei , Wang Ming , Yang Fan , Thomas Quentin Angelo , Xue Yan , Zhang Yaxin , Liu Wanlu , Jami-Alahmadi Yasaman , Xu Linhao , Feng Suhua , Marquardt Sebastian , Wohlschlegel James A. , Ausin Israel , Jacobsen Steven E. 
Published: September 2022

AbstractHistone chaperones and chromatin remodelers control nucleosome dynamics, which are essential for transcription, replication, and DNA repair. The histone chaperone Anti-Silencing Factor 1 (ASF1) plays a central role in facilitating CAF-1-mediated replication-dependent H3.1 deposition and HIRA-mediated replication-independent H3.3 deposition in yeast and metazoans. Whether ASF1 function is evolutionarily conserved in plants is unknown. Here, we show that Arabidopsis ASF1 proteins display a preference for the HIRA complex. Simultaneous mutation of both Arabidopsis ASF1 genes caused a decrease in chromatin density and ectopic H3.1 occupancy at loci typically enriched with H3.3. Genetic, transcriptomic, and proteomic data indicate that ASF1 proteins strongly prefers the HIRA complex over CAF-1. asf1 mutants also displayed an increase in spurious Pol II transcriptional initiation and showed defects in the maintenance of gene body CG DNA methylation and in the distribution of histone modifications. Furthermore, ectopic targeting of ASF1 caused excessive histone deposition, less accessible chromatin, and gene silencing. These findings reveal the importance of ASF1-mediated histone deposition for proper epigenetic regulation of the genome.
PhysiPKPD: A pharmacokinetics and pharmacodynamics module for PhysiCell
Authors: Bergman Daniel , Marazzi Lauren , Chowkwale Mukti , Maheshvare M Deepa , Bidanta Supriya , Mapder Tarunendu , Li Jialun 
Published: September 2022

AbstractPharmacokinetics and pharmacodynamics are key considerations in any study of molecular therapies. It is thus imperative to factor their effects in to any in silico model of biological tissue involving such therapies. Furthermore, creation of a standardized and flexible framework will benefit the community by increasing access to such modules and enhancing their communicability. PhysiCell is an open source physics-based cell simulator, i.e. a platform for modeling biological tissue, that is quickly being adopted and utilized by the mathematical biology community. We present here PhysiPKPD, an open source PhysiCell-based package that allows users to include PKPD in PhysiCell models.Availability & ImplementationThe source code for PhysiPKPD is located here: https://github.com/drbergman/PhysiPKPD.
Phenotypic profiling of macrocyclic lactones on parasitic Schistosoma flatworms
Authors: Ryan Kaetlyn T. , Wheeler Nicolas J. , Kamara Isaac K. , Johnson Hailey , Humphries Judith E , Zamanian Mostafa , Chan John D. 
Published: September 2022

AbstractMacrocyclic lactones are front-line therapies for parasitic roundworm infections, but there are no comprehensive studies on the activity of this drug class against parasitic flatworms. Ivermectin is well known to be inactive against flatworms. However, the structure-activity relationship of macrocyclic lactones may vary across phyla, and it is entirely possible other members of this drug class do in fact show antiparasitic activity on flatworms. For example, there are several reports hinting at the anti-schistosomal activity of doramectin and moxidectin. To explore this class further, we developed an automated imaging assay combined with measurement of lactate levels from worm media. This assay was applied to the screening of 21 macrocyclic lactones (avermectins, milbemycins and others such as spinosyns) against adult schistosomes. These in vitro assays identified several macrocyclic lactones (emamectin, milbemycin oxime, and the moxidectin metabolite 23-ketonemadectin) that caused contractile paralysis and lack of lactate production. Several of these were also active against miracidia, a juvenile life cycle stage of the parasite. Hits prioritized from these in vitro assays were administered to mice harboring patent schistosome infections. However, no reduction in worm burden was observed. Nevertheless, these data show the utility of a multiplexed in vitro screening platform to quantitatively assess drug action and prioritize hits in a chemical series for in vivo studies. While the prototypical macrocyclic lactone ivermectin displays minimal activity against adult Schistosoma mansoni, this family of compounds does contain schistocidal compounds which may serve as a starting point for development of new anti-flatworm chemotherapies.
Life expectancy, quality of life, and hope among Japanese patients receiving home medical care
Authors: Yasunaka Masakazu , Tsugihashi Yukio , Hayashi Shinu , Iida Hidekazu , Hirose Misaki , Shirahige Yutaka , Kurita Noriaki ,   the ZEVIOUS group
Published: September 2022

ABSTRACTBackgroundSpiritual care should be included in home medical care for patients with limited life expectancy. However, the effect of shortened life expectancy on patients’ quality of life (QOL) and hopes is poorly understood.MethodsThis multicenter cross-sectional study involved 29 home medical care centers in Japan. Exposures were life expectancy (≥ one year / ≥ six months to < one year / < six months) as assessed by home medical care physicians. The outcomes were QOL in home medical care measured via the Quality-of-Life Scale for Elderly Patients Receiving Professional Home Care (QOL-HC), the domain scores of health-related hope (“health,” “role and connectedness,” and “something to live for”), and decrease in life functioning measured using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Linear mixed models were fitted for analyses, with the facilities treated as clusters.ResultsShorter life expectancy was associated with higher WHODAS 2.0 scores and significantly lower “something to live for” scores (< six months vs. ≥ one year). In contrast, “role and connectedness” scores did not change remarkably with decreased life expectancy, whereas QOL-HC scores were significantly higher with shorter life expectancy.ConclusionHome medical care physicians who engage in spiritual care should facilitate thoughtful dialogue with their patients by recognizing declines in life functions and hope for fulfillment, which are associated with short life expectancy.
Pregnant women’s attitudes and behaviours towards antenatal vaccination against Influenza and COVID-19 in the Liverpool City Region, United Kingdom: cross-sectional survey
Authors: Kilada Samantha , French Neil , Perkins Elizabeth , Hungerford Dan 
Published: September 2022

AbstractObjectiveInfluenza poses a serious health risk to pregnant women and their babies. Despite this risk, influenza vaccine uptake in pregnant women in the UK is less than 50%. Little is known about how COVID-19 affects pregnant women, but its management may affect attitudes and behaviours towards vaccination in pregnancy. The study objectives were to establish attitudes and knowledge of pregnant women towards influenza disease and influenza vaccination and to compare these to attitudes and knowledge about COVID-19 and COVID-19 vaccination.DesignA cross-sectional survey was conducted using an online questionnaire distributed through local advertisement and social media outlets. Information was sought on attitudes and knowledge of influenza and COVID-19 and their respective vaccines.Participants and settingPregnant women residing in Liverpool City Region, UKResultsOf the 237 respondents, 73.8% reported receiving an influenza vaccine. Over half (56.5%) perceived themselves to be at risk from influenza, 70.5% believed that if they got influenza, their baby would get ill, and 64.6% believed getting influenza could hurt their baby, 60.3% believed that the influenza vaccine would prevent their baby from getting ill, and 70.8% believed it would protect their baby. Only 32.9% of respondents stated they would receive the COVID-19 vaccine if it were available to them. However, 80.2% stated they would receive a COVID-19 vaccine if they were not pregnant. Most of the women stated that they would accept a vaccine if recommended to them by healthcare professionals.ConclusionsAcceptance of the influenza and COVID-19 vaccines during pregnancy seems to be more related to the safety of the baby rather than the mother. Women perceived their child to be more at risk than themselves. Information about influenza and COVID-19 vaccine safety as well as healthcare provider recommendations play an important role in vaccine uptake in pregnant women.Strengths and limitations of this studyThe study provides information on how a pandemic affects vaccine attitudes and behaviours during pregnancy.The study compares and contrasts attitudes and behaviours towards influenza and COVID-19 vaccines.The study provides new information relating to barriers to COVID-19 vaccine acceptance and provides insights into mechanisms for improving uptake.The sample size is small and self-selected which might lead to an over-representation of women likely to accept or have strong opinions on vaccinations.Responses to the questions on vaccine status are self-reported, not provided from healthcare records.
Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates
Authors: Zhang Chenqi , Herbig Maik , Zhou Yuqi , Nishikawa Masako , Shifat-E-Rabbi Mohammad , Kanno Hiroshi , Yang Ruoxi , Ibayashi Yuma , Xiao Ting-Hui , Rohde Gustavo K. , Sato Masataka , Kodera Satoshi , Daimon Masao , Yatomi Yutaka , Goda Keisuke 
Published: September 2022

ABSTRACTMicrovascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.