bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic Status and Women’s Mental Health and Wellbeing in Male-Factor Infertility Marital Circumstances: A Scoping Review
Authors: Umoh Nanji R. 
Published: October 2022

AbstractBackgroundInfertility is established where frequent intercourse and non-contraceptive use over 12 to 24-month periods do not result in live births. It is an underemphasized global public health challenge occurring mostly in countries with the highest fertility rates. Infertility can be female- or male-factor-based, combined, unexplained, or impaired. Fertility research emphasizes socio-cultural beliefs, patriarchy, insufficient distinctions between masculinity and virility, etc., as impacting women’s mental health and wellbeing. Conversely, research, policies, and interventions underemphasize the male-factor as central to reproduction. This is counter-productive for their female counterparts in the reproductive equation and contributes to gaps in reproductive health literature. Male-factor infertility, a sensitive, long-neglected public health issue caused by genetic and environmental factors, constitutes 20% of infertility cases globally. The biopsychosocial impacts of childlessness on women in male-factor infertility circumstances are almost equally deleterious across social groups and regions.ObjectiveTo present a scoping review of evidence on the extent to which reproductive health literature recognizes socioeconomic status as central to women’s mental health and wellbeing in male-factor infertility circumstances.MethodsLiterature was mapped across five databases (MedlinePlus, Google Scholar, PubMed, ScienceDirect and Publons Web of Science) without restrictions to geographical regions. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist-2018 was the review protocol.Results12 out of 2582 screened articles met the eligibility criteria. The impacts of childlessness on women in male-factor infertility circumstances are similar across regions, but aggravated by socioeconomic circumstances, particularly in low- and middle-income countries (LMICs) and societies that emphasize childbearing. Women with relatively high socioeconomic statuses and access to New/Assisted Reproduction Technologies (NRTs/ARTs) enjoy better mental health and wellbeing.Discussion/ConclusionThe Social Determinants of Health (SDHs) provided the analytical framework. The socioeconomic status influences the quality of the women’s overall wellbeing in male-factor infertility circumstances, with implications for access to and affordability of New/Assisted Reproduction Technologies (NRTs/ARTs) and other related male-factor infertility treatment options. The deleterious impacts are more for those who are unable to afford the fertility treatments. Asides this socioeconomic context of infertility, a politico-legal context exacerbates the suffering of women in male-factor infertility circumstances, through policy gaps that exist in the provision of interventions to cater to the needs of socioeconomically disadvantaged women.
Repeat polymorphisms in non-coding DNA underlie top genetic risk loci for glaucoma and colorectal cancer
Authors: Mukamel Ronen E. , Handsaker Robert E. , Sherman Maxwell A. , Barton Alison R. , Hujoel Margaux L. A. , McCarroll Steven A. , Loh Po-Ru 
Published: October 2022

AbstractMany regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). We recently showed that protein-coding VNTRs underlie some of the strongest known genetic associations with diverse phenotypes. Here, we assessed the phenotypic impact of VNTRs genome-wide, 99% of which lie in non-coding regions. We applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants. Association and statistical fine-mapping analyses identified 107 VNTR-phenotype associations (involving 58 VNTRs) that were assigned a high probability of VNTR causality (PIP≥0.5). Non-coding VNTRs atTMCO1andEIF3Happeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2- fold risk range across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health.
The role of uncertainty and negative feedback loops in the evolution of induced immune defenses
Authors: Asgari Danial , Stewart Alexander J. , Meisel Richard P. 
Published: October 2022

AbstractOrganisms use constitutive or induced defenses against pathogens, parasites, and herbivores. Constitutive defenses are constantly on, whereas induced defenses are activated upon exposure to an enemy. Constitutive and induced defenses each have costs and benefits, which can affect the type of defense that evolves in response to pathogens. Previous models that compared the two lacked mechanistic details about host defense, did not consider pathogen proliferation rates, or lacked both features. To address this gap, we developed a detailed mechanistic model of the well-characterizedDrosophila melanogasterimmune signaling network. We evaluated the factors favoring the evolution of constitutive and induced defenses by comparing the fitness of each strategy under stochastic fly-bacteria interactions. We show that an induced defense is favored when bacteria are at low density, heterogeneously distributed, or have fluctuating distributions in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate. We therefore conclude that an induced immune defense is favored in environments where bacterial encounters are uncertain—because of heterogeneity in spatial or temporal distributions—but that benefit depends on the mechanism of induction and pathogen properties.
Evolutionary impact of codon specific translation errors at the proteome scale
Authors: Landerer Cedric , Pöhls Jonas , Toth-Petroczy Agnes 
Published: October 2022

SummaryErrors in protein synthesis can lead to non-genetic phenotypic mutations, which contribute to generating a wide range of protein diversity. There are currently no methods to measure proteome-wide amino acid misincorporations in a high-throughput fashion, limiting their detection to specific sites and few codon-anticodon pairs. Therefore, it has been technically challenging to estimate the evolutionary impact of translation errors. Here, we developed a computational pipeline, integrated with a novel mechanistic model of translation errors, which can detect translation errors across organisms and conditions. We revealed hundreds of thousands of amino acid misincorporations and a rugged error landscape in datasets ofE. coliandS. cerevisiae. We provide proteome-wide evidence of how codon choice can locally reduce translation errors. Our analysis indicates that the translation machinery prevents strongly deleterious misincorporations while allowing for advantageous ones, and the presence of missing tRNAs would increase codon-anticodon cross-reactivity and misincorporation error rates.
Semaphorin 4B is an ADAM17-cleaved inhibitor of adipocyte thermogenesis
Authors: Amin Abdulbasit , Badenes Marina , Tüshaus Johanna , de Carvalho Érsika , Burbridge Emma , Faísca Pedro , Trávníčková Květa , Barros André , Carobbio Stefania , Domingos Pedro , Vidal-Puig Antonio , Moita Luís , Maguire Sarah , Stříšovský Kvido , Lichtenthaler Stefan F. , Adrain Colin 
Published: October 2022

AbstractObjectiveThe metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.MethodsWe used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.ResultsADAM17adipoq-creΔ/Δmice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues that acts to dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to dampen the expression of genes involved in thermogenesis, adipogenesis, lipid uptake, storage and catabolism.ConclusionOur findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that may act to limit uncontrolled energy depletion during thermogenesis.
Regional variations in primary percutaneous coronary intervention for acute myocardial infarction patients: A trajectory analysis using the national claims database in Japan
Authors: Itoshima Hisashi , Shin Jung-ho , Sasaki Noriko , Goto Etsu , Kunisawa Susumu , Imanaka Yuichi 
Published: October 2022

v.AbstractBACKGROUNDPrevious studies have demonstrated geographical disparities regarding the quality of care for acute myocardial infarction (AMI). The aim of this study was two-folds: first, to calculate the proportion of patients with AMI who received primary percutaneous coronary interventions (pPCIs) by secondary medical areas (SMAs), which provide general inpatient care, as a quality indicator (QI) of the process of AMI practice. Second, to identify patterns in their trajectories and to investigate the factors related to regional differences in their trajectories.METHODSWe included patients hospitalized with AMI between April 2014 and March 2020 from the national health insurance claims database in Japan and calculated the proportion of pPCIs across 335 SMAs and fiscal years. Using these proportions, we conducted group-based trajectory modeling to identify groups that shared similar trajectories of the proportions. In addition, we investigated area-level factors that were associated with the different trajectories.RESULTSThe median (interquartile range) proportions of pPCIs by SMAs were 63.5% (52.9% to 70.5%) in FY 2014 and 69.6% (63.3% to 74.2%) in FY 2020. Four groups, named low to low (LL; n =, low to middle (LM; n = 16), middle to middle (MM; n = 68), and high to high (HH; n = 208), were identified from our trajectory analysis. The HH and MM groups had higher population densities and higher numbers of physicians and cardiologists per capita than the LL and LM groups. The LL and LM groups had similar numbers of physicians per capita, but the number of cardiologists per capita in the LM group increased over the years of the study compared with the LL group.CONCLUSIONThe trajectory of the proportion of PCIs for AMI patients identified groups of SMAs. Among the four groups, the LM group showed an increasing trend in the proportions of pPCIs, whereas the three other groups showed relatively stable trends.vi.Summary boxesWhat is already known on this topicThe quality of health care for acute myocardial infarction (AMI) patients varies across regions.Door-to-balloon time is associated with patient outcomes, and one of the most easily measurable indicators is the provision of rapid treatment for AMI patients.What this study addsThe study demonstrated that there were not only cross-sectional regional differences in the proportion of PCIs for AMI patients but also differences in these trajectories.The cross-sectional regional differences in the proportion of pPCIs were maintained in many SMAs, but there were a few SMAs that increased yearly.
Quantifying changes in the IFR and IHR over 23 months of the SARS-CoV-2 pandemic in England
Authors: Eales Oliver , Haw David , Wang Haowei , Atchison Christina , Ashby Deborah , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Donnelly Christl A. , Chadeau-Hyam Marc , Elliott Paul , Riley Steven 
Published: October 2022

AbstractBackgroundThe relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity in England approximately monthly from May 2020 to 31 March 2022. This period covers widespread circulation of the original strain, the emergence of the Alpha, Delta and Omicron variants and the rollout of England’s mass vaccination campaign.MethodsHere, we explore this changing relationship between prevalence of swab positivity and the infection fatality rate (IFR) and infection hospitalisation rate (IHR) over 23 months of the pandemic in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models and Bayesian P-spline models. We analyse data for all age groups together, as well as in two sub-groups: those aged 65 and over and those aged 64 and under.ResultsDuring 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late-2021/early-2022 the IFR and IHR had both decreased to 0.097% and 0.76% respectively. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta’s emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR of the virus decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late-2021/early-2022 these time-lags had decreased to 7 days for hospitalisations, and 18 days for deaths.ConclusionEven though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on IHR and IFR. As investments in community surveillance are scaled back, alternative methods should be developed to accurately track the ever changing relationship between infection, hospitalisation and death.
FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors
Authors: Nguyen-Dien Giang Thanh , Kozul Keri-Lyn , Cui Yi , Townsend Brendan , Kulkarni Prajakta Gosavi , Ooi Soo Siang , Marzio Antonio , Carrodus Nissa , Zuryn Steven , Pagano Michele , Parton Robert G. , Lazarou Michael , Millard Sean , Taylor Robert W. , Collins Brett M. , Jones Mathew J.K. , Pagan Julia K. 
Published: October 2022

AbstractCells selectively remove damaged or excessive mitochondria through mitophagy, a specialized form of autophagy, to maintain mitochondrial quality and quantity. Mitophagy is induced in response to diverse conditions, including hypoxia, cellular differentiation, and mitochondrial damage. However, the mechanisms by which cells remove specific dysfunctional mitochondria under steady-state conditions to fine-tune mitochondrial content are not well understood. Here, we report that SCFFBXL4, an SKP1/CUL1/F-box protein ubiquitin ligase complex, localizes to the mitochondrial outer membrane in unstressed cells and mediates the constitutive ubiquitylation and degradation of the mitophagy receptors NIX and BNIP3 to suppress basal levels of mitophagy. We demonstrate that, unlike wild-type FBXL4, pathogenic variants of FBXL4 that cause encephalopathic mtDNA depletion syndrome (MTDPS13), do not efficiently interact with the core SCF ubiquitin ligase machinery or mediate the degradation of NIX and BNIP3. Thus, we reveal a molecular mechanism that actively suppresses mitophagy via preventing NIX and BNIP3 accumulation and propose that excessive basal mitophagy in the FBXL4-associated mtDNA depletion syndrome is caused by dysregulation of NIX and BNIP3 turnover.
Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation
Authors: De-Souza Evandro A. , Thompson Maximillian A. , Taylor Rebecca C. 
Published: October 2022

AbstractAnimals rely on chemosensory cues to survive in pathogen-rich environments. InC. elegans, pathogenic bacteria are known to trigger aversive behaviors through neuronal perception, and to activate molecular defenses throughout the animal. This suggests that neurons may be able to coordinate the activation of organism-wide defensive responses upon pathogen perception. We find that exposure to volatile pathogen-associated compounds induces cell non-autonomous activation of the endoplasmic reticulum unfolded protein response (UPRER) in peripheral tissues followingxbp-1splicing in neurons. This odorant-induced UPRERactivation is dependent upon transforming growth factor beta (TGF-β) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Our data suggest that the cell non-autonomous UPRERrewires organismal proteostasis in response to pathogen detection, pre-empting the arrival of proteotoxic stress. Thus, chemosensation of particular odors may be a novel way to manipulate stress responses and longevity.
Multiscale Modeling of MT1-MMP-Mediated Cell Migration: Destabilization of Cell-Matrix Adhesion
Authors: Andasari V. , Zaman M. 
Published: October 2022

AbstractOne of several ways MT1-MMP promotes cell migration is by modifying cell adhesion properties. MT1-MMP directly processes cell adhesion properties by shedding cell transmembrane receptors that attach cells to the extracellular matrix (ECM). The shedding leads to the destabilization and disassembly of firm cell-matrix adhesion that holds cells in their stationary position, prompting cells to migrate. In this paper, we present a multiscale mathematical model of single cell migration driven by MT1-MMP destabilization of cell-matrix adhesion. The dynamics of MT1-MMP are modeled using a system of differential equations that are integrated with the Cellular Potts Model (CPM) for a combined modeling at the intracellular and cellular scale, respectively. The CPM is extended to include a local feedback mechanism from MT1-MMP on the membrane that enhances cell membrane fluctuations, resulting in actively migrating cells. The results of computational simulation show that MT1-MMP is capable of destabilizing strong cell-matrix adhesion and stimulating cell migration, and at the same time, also producing cell polarization and motile cell morphology.
Anin vivoavian model of human melanoma to perform rapid and robust preclinical studies
Authors: Jarrosson Loraine , Dalle Stéphane , Costechareyre Clélia , Tang Yaqi , Grimont Maxime , Plaschka Maud , Lacourrège Marjorie , Teinturier Romain , Le Bouar Myrtille , Maucort-Boulch Delphine , Eberhardt Anaïs , Castellani Valérie , Caramel Julie , Delloye-Bourgeois Céline 
Published: October 2022

AbstractMetastatic melanoma patients carrying a BRAFV600mutation can be treated with BRAF inhibitors (BRAFi), in combination with MEK inhibitors (MEKi), but innate and acquired resistance invariably occurs. Resistance can involve transcriptional- and epigenetic-based phenotypic adaptations, as yet unpredictable. Predicting patient response to targeted therapies is crucial to guide clinical decision. We describe here the development of a highly efficient patient-derived xenograft model adapted to patient melanoma biopsies, using the avian embryo as a host (AVI-PDX™). In thisin vivoparadigm, we depict a fast and reproducible tumor engraftment of patient samples within the embryonic skin, preserving key molecular and phenotypic features. We show that sensitivity and resistance to BRAFi/MEKi targeted therapies can be reliably modeled in these AVI-PDX™, as well as synergies with other drugs, such as HDACi. We further provide proof-of-concept that the AVI-PDX™models the diversity of responses of melanoma patients to BRAFi/MEKi, within days, hence positioning it as a valuable tool for the design of personalized medicine assays and for the evaluation of novel combination strategies.
Tissue-specific transcriptomes reveal mechanisms of microbiome regulation in an ancient fish
Authors: Thorstensen Matt J. , Weinrauch Alyssa M. , Bugg William S. , Jeffries Ken M. , Anderson W. Gary 
Published: October 2022

AbstractThe lake sturgeon (Acipenser fulvescens) is an ancient, octoploid fish faced with conservation challenges across its range in North America but a lack of genomic resources has hindered molecular research in the species. To support such research we aimed to provide a transcriptomic database from 13 tissues: brain, esophagus, gill, head kidney, heart, white muscle, liver, glandular stomach, muscular stomach, anterior intestine, pyloric cecum, spiral valve, and rectum. The transcriptomes for each tissue were sequenced and assembled individually from a mean of 98.3 million (±38.9 million std. dev.) reads each. In addition, an overall transcriptome was assembled and annotated with all data used for each tissue-specific transcriptome. All assembled transcriptomes and their annotations were made publicly available as a scientific resource. The non-gut transcriptomes provide important resources for many research avenues, however, the gut represents a compartmentalized organ system with compartmentalized functions and the sequenced gut tissues were from each of these portions. Therefore, we focused our analysis on mRNA transcribed in different tissues of the gut and explored evidence of microbiome regulation. Gene set enrichment analyses were used to reveal the presence of photoperiod and circadian-related transcripts in the pyloric caecum, which may support periodicity in lake sturgeon digestion. Similar analyses were used to identify different types of innate immune regulation across the gut, while analyses of unique transcripts annotated to microbes revealed heterogeneous genera and genes among different gut tissues. The present results provide a scientific resource and information about the mechanisms of compartmentalized function across gut tissues in a phylogenetically ancient vertebrate.