bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a livelihood intervention on gender roles and relationship power among people with HIV
Authors: Sheira Lila A. , Wekesa Pauline , Cohen Craig R. , Weke Elly , Frongillo Edward A. , Mocello A. Rain , Dworkin Shari L. , Burger Rachel L. , Weiser Sheri D. , Bukusi Elizabeth A. 
Published: October 2023

Objective:
To evaluate the impact of an agricultural livelihood intervention on gender role conflict and sexual relationship power among people with HIV (PWH) in western Kenya.

Design:
Study participants were enrolled in Shamba Maisha, a cluster randomized controlled trial of an agricultural intervention conducted among PWH across 16 health facilities during 2016–2020. Intervention participants received a water pump, seeds, and agricultural and financial training; control participants received standard of HIV care.

Methods:
We assessed men's views on masculinity and gender roles via the validated gender role conflict score (GRCS; range 18–78, higher = greater gender role conflict). We measured gender power imbalances among women via the validated Sexual Relationship Power Scale (SRPS), which combines subscales of relationship control and decision-making dominance (range 1–4, higher = female holds more power). We compared changes over the study period by arm using longitudinal multilevel difference-in-difference linear regression models accounting for clustering of facilities using the intention-to-treat cohort.

Results:
We enrolled 720 participants (366 intervention, 354 control); 2-year retention was 94%. Median age was 40 and approximately 55% of participants were female. Among men, after 24-months the decrease in GRCS scores was 4.3 points greater in the intervention than the control arm (P < 0.001). Among women, the intervention resulted in 0.25 points greater increase in the SRPS compared to the control arm (P < 0.001).

Conclusions:

Shamba Maisha resulted in less gender role conflict in men and greater sexual relationship power for women. Agricultural livelihood interventions may be a powerful tool to improve gender power imbalances, which may subsequently mitigate poverty and food insecurity.
Longitudinal associations of sustained low or high income and income variability with incident cardiovascular disease in individuals with type 2 diabetes: a retrospective population-based cohort study
Authors: Park Yong-Moon Mark , Baek Jong Ha , Lee Hong Seok , Elfassy Tali , Brown Clare C. , Schootman Mario , Narcisse Marie-Rachelle , Ko Seung-Hyun , McElfish Pearl A. , Thomsen Michael R. , Amick Benjamin C. , Lee Seong-Su , Han Kyungdo 
Published: October 2023

ABSTRACTBackground and AimsLongitudinal change in income is crucial in explaining cardiovascular health inequalities, but there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D).MethodsUsing a nationally representative sample from the Korean Health Insurance Service database, 1,528,108 adults with T2D aged 30-64 years and no history of CVD were enrolled between 2009-2012 (mean follow-up of 7.3 years). Using monthly health insurance premiums information, income levels were assessed annually for 4 years before the baseline year. Income variability was defined as the intraindividual standard deviation of the percent change in income across 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, stroke, and heart failure) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders.ResultsSustained low income (i.e., lowest income quartile) over 5 years was associated with increased CVD risk (HRn=5yearsvs.n=0years1.38, 95% CI 1.35-1.41; Ptrend<0.0001), whereas sustained high income (i.e., highest income quartile) was associated with decreased CVD risk (HR 0.71n=5yearsvs.n=0years95% CI 0.70-0.72; Ptrend<0.0001). High-income variability was associated with increased CVD risk (HRhighestvs.lowestquartile1.25, 95% CI 1.22-1.27; Ptrend<0.001). Individuals who experienced an income decline across 5 years leading up to baseline had increased CVD risk, particularly in a decrease to the lowest income level (i.e., Medical Aids beneficiaries), regardless of initial income status. Sensitivity analyses, including potential mediators, such as lifestyle-related factors and obesity, supported the results.ConclusionsAmong non-elderly Korean adults with T2D, sustained low income, higher income variability, and income declines were associated with increased CVD risk. Our findings highlight the need to understand better the mechanisms by which income dynamics impact CVD risk among individuals with T2D.
Epigenetic age and socioeconomic status contribute to racial disparities in cognitive and functional aging between Black and White older Americans
Authors: Yannatos Isabel , Stites Shana D. , Boen Courtney , Xie Sharon X. , Brown Rebecca T. , McMillan Corey T. 
Published: October 2023

AbstractEpigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.
The role of socio-economic disparities in the relative success of SARS-CoV-2 variants in New York City in early 2021
Authors: Vasylyeva Tetyana I. , Havens Jennifer L. , Wang Jade C. , Luoma Elizabeth , Hassler Gabriel W. , Amin Helly , Di Lonardo Steve , Taki Faten , Omoregie Enoma , Hughes Scott , Wertheim Joel O. 
Published: October 2023

ABSTRACTBackgroundSocio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation SARS-CoV-2 variants during the second wave in NYC.MethodsWe tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework.FindingsSeropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas.InterpretationDuring the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity.FundingWe acknowledge funding from the National Institutes of Health and the Centers for Disease Control and Prevention.
HPV detection patterns in young women from the PAPCLEAR longitudinal study: implications for HPV screening policies
Authors: Beneteau Thomas , Groc Soraya , Murall Carmen Lia , Boué Vanina , Elie Baptiste , Tessandier Nicolas , Bernat Claire , Bonneau Marine , Foulongne Vincent , Graf Christelle , Grasset Sophie , Rahmoun Massilva , Segondy Michel , Tribout Vincent , Reynes Jacques , Selinger Christian , Boulle Nathalie , Bravo Ignacio G. , Sofonea Mircea T. , Alizon Samuel 
Published: October 2023

AbstractObjectivesHPV infections are ubiquitous. For most infections, we lose track of the presence of the virus in host in less than three years after the start of infection. The mechanisms regulating the persistence of HPV infection are still partially understood. In this work, we focus on incident HPV detection in young women and we characterise the dynamics of these infections and evaluate the effect of genotype and host socio-economic factors on the duration of HPV detection and time between detection.MethodsWe investigated human papillomavirus (HPV) genotype detection patterns in 182 young women in Montpellier, France. We relied on SPF10-LiPA25 screening assay for the simultaneous de-tection of 25 HPV genotypes. We used survival analysis tools with frailty effects to investigate the contribution of viral and host factors to variations in the time of HPV detectability, time of first incident detection, and time before re-detection.ResultsWomen of the PAPCLEAR cohort experienced numerous positive HPV events, including frequent redetection of the same genotype. We retrieve classical results that HR-genotypes are detected for longer duration than LR-genotypes. HR-genotypes were also more liekly to be detected than LR-genotypes during the follow-up. The number of lifetime sexual partner was strongly associated with increased risk of new positive detection while vaccination was related to a lower risk of displaying incident infections. Covariates related to socio-economic difficulties were associated with longer duration of HPV positivity.ConclusionsYoung women display numerous event of HPV detection, with frequent codetections of multiple genotypes at the same time and redetection of the same type after periods of no detection. These new detection are almost certainly the result of new acquisition from sexual partners, with little evidence of re-emergence of latent infections. A better characterisation of transient infections might help unveil doubts and misconception on HPV physiopathology, favouring adherence to preventive policies.
Multi-modal transcriptomic analysis unravels enrichment of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer
Authors: Sahoo Sarthak , Ramu Soundharya , Nair Madhumathy G , Pillai Maalavika , San Juan Beatriz P , Milioli Heloisa Zaccaron , Mandal Susmita , Naidu Chandrakala M , Mavatkar Apoorva D , Subramaniam Harini , Neogi Arpita G , Chaffer Christine L , Prabhu Jyothi S , Somarelli Jason A , Jolly Mohit Kumar 
Published: October 2023

AbstractIntra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. It manifests along multiple phenotypic axes and decoding the interconnections among these different axes is crucial to understand its molecular origins and to develop novel therapeutic strategies to control it. Here, we use multi-modal transcriptomic data analysis – bulk, single-cell and spatial transcriptomics – from breast cancer cell lines and primary tumor samples, to identify associations between epithelial-mesenchymal transition (EMT) and luminal-basal plasticity – two key processes that enable heterogeneity. We show that luminal breast cancer strongly associates with an epithelial cell state, but basal breast cancer is associated with hybrid epithelial/mesenchymal phenotype(s) and higher phenotypic heterogeneity. These patterns were inherent in methylation profiles, suggesting an epigenetic crosstalk between EMT and lineage plasticity in breast cancer. Mathematical modelling of core underlying gene regulatory networks representative of the crosstalk between the luminal-basal and epithelial-mesenchymal axes recapitulate and thus elucidate mechanistic underpinnings of the observed associations from transcriptomic data. Our systems-based approach integrating multi-modal data analysis with mechanism-based modeling offers a predictive framework to characterize intra-tumor heterogeneity and to identify possible interventions to restrict it.
Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2
Authors: Myers Bianca L. , Brayer Kathryn J. , Paez-Beltran Luis E. , Keith Matthew S. , Suzuki Hideaki , Newville Jessie , Anderson Rebekka H. , Lo Yunee , Mertz Conner M. , Kollipara Rahul , Borromeo Mark D. , Bachoo Robert M. , Johnson Jane E. , Vue Tou Yia 
Published: October 2023

ABSTRACTGlioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM. Subsequently, the dynamic levels and reciprocal binding of ASCL1 and OLIG2 to each other and to downstream target genes then determine the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in defining GSCs by upregulating a collection of ribosomal protein, mitochondrial, neural stem cell (NSC), and cancer metastasis genes – all essential for sustaining the high proliferation, migration, and therapeutic resistance of GSCs.
Bile Acids Serve As Endogenous Antagonists Of The Leukemia Inhibitory Factor (LIF) Receptor in Oncogenesis
Authors: Di Giorgio Cristina , Morretta Elva , Lupia Antonio , Bellini Rachele , Massa Carmen , Urbani Ginevra , Bordoni Martina , Marchianò Silvia , Rapacciuolo Pasquale , Finamore Claudia , Sepe Valentina , Monti Maria Chiara , Moraca Federica , Natalizi Nicola , Graziosi Luigina , Distrutti Eleonora , Biagioli Michele , Catalanotti Bruno , Donini Annibale , Zampella Angela , Fiorucci Stefano 
Published: October 2023

SummaryThe leukemia inhibitory factor (LIF) is member of IL-6 family of cytokines involved immune regulation, morphogenesis and oncogenesis. In cancer tissues, LIF binds a heterodimeric receptor (LIFR), formed by a LIFRβ subunit and glycoprotein(gp)130, promoting epithelial mesenchymal transition and cell growth. Bile acids are cholesterol metabolites generated at the interface of host metabolism and the intestinal microbiota. Here we demonstrated that bile acids serve as endogenous antagonist to LIFR in oncogenesis. The tissue characterization of bile acids content in non-cancer and cancer biopsy pairs from gastric adenocarcinomas (GC) demonstrated that bile acids accumulate within cancer tissues, with glyco-deoxycholic acid (GDCA) functioning as negative regulator of LIFR expression. In patient-derived organoids (hPDOs) from GC patients, GDCA reverses LIF-induced stemness and proliferation. In summary, we have identified the secondary bile acids as the first endogenous antagonist to LIFR supporting a development of bile acid-based therapies in LIF-mediated oncogenesis.
Physical activity regulates the immune response to breast cancer by a hematopoietic stem cell-autonomous mechanism
Authors: Khair Lyne , Hayes Katherine , Tutto Amanda , Samant Amruta , Ferreira Lindsay , Nguyen Tammy T. , Brehm Michael , Messina Louis M. 
Published: October 2023

ABSTRACTPhysical activity is a modifiable lifestyle factor that is associated with a decreased risk for the development of breast cancer. While the exact mechanisms for the reduction in cancer risk due to physical activity are largely unknown, it is postulated that the biological reduction in cancer risk is driven by improvements in inflammation and immune function with exercise. Hematopoietic stem cells (HSCs) are the progenitor for all of the cells of the immune system and are involved in cancer immunosurveillance through differentiation into cytotoxic cell population. In this study, we investigate the role of physical activity (PA) in a spontaneously occurring model of breast cancer over time, with a focus on tumor incidence, circulating and tumor-infiltrating immune cells as well gene expression profiles of tumors and hematopoietic stem cells. Furthermore, we show that, in addition to a direct effect of PA on the immune cells of tumor-bearing mice, PA reduces the oxidative stress in HSCs of wildtype and tumor-bearing mice, and by doing so, alters the differentiation of the HSCs towards T cells in order to enhance cancer immunosurveillance.
Three distinct gamma oscillatory networks within cortical columns in macaque monkeys’ area V1
Authors: Drebitz Eric , Rausch Lukas-Paul , Gil Esperanza Domingo , Kreiter Andreas K. 
Published: October 2023

AbstractA fundamental property of the neocortex is its columnar organization in many species. Generally, neurons of the same column share stimulus preferences and have strong anatomical connections across layers. These features suggest that neurons within a column operate as one unified network. Other features, like the different patterns of input and output connections of neurons located in separate layers and systematic differences in feature tuning, hint at a more segregated and possibly flexible functional organization of neurons within a column. To distinguish between these views of columnar processing, we conducted laminar recordings in macaques’ area V1 while they performed a demanding attention task. We found three separate regions with strong gamma oscillatory current source density (CSD) signals, one each in the supragranular, granular, and infragranular laminar domains. Their characteristics differed significantly in terms of their dominant gamma frequency and attention-dependent modulation of their gramma power and gamma frequency. In line, spiking activity in the supragranular, infragranular, and upper part of the granular domain exhibited strong phase coherence with their domain’s CSD signals but showed much weaker coherence with the other domains’ CSD signals. These results indicate that columnar processing involves a certain degree of independence between neurons in the three laminar domains, consistent with the assumption of multiple, separate intracolumnar ensembles. Such a functional organization offers various possibilities for dynamic network configuration, indicating that neurons in a column are not restricted to operate as one unified network. Thus, the findings open interesting new possibilities for future concepts and investigations on flexible, dynamic cortical ensemble formation and selective information processing.
Development of properly-polarized trophoblast stem cell-derived organoids to model early human pregnancy
Authors: Zhou J , Sheridan MA , Tian Y , Dahlgren KJ , Messler M , Peng T , Ezashi T , Schulz LC , Ulery BD , Roberts RM , Schust DJ 
Published: October 2023

SummaryThe development of human trophoblast stem cells (hTSC) and stem cell-derived trophoblast organoids has enabled investigation of placental physiology and disease and early maternal-fetal interactions during a stage of human pregnancy that previously had been severely restricted. A key shortcoming in existing trophoblast organoid methodologies is the non-physiologic position of the syncytiotrophoblast (STB) within the inner portion of the organoid, which neither recapitulates placental villous morphologyin vivonor allows for facile modeling of STB exposure to the endometrium or the contents of the intervillous space. Here we have successfully established properly-polarized human trophoblast stem cell (hTSC)-sourced organoids with STB forming on the surface of the organoid. These organoids can also be induced to give rise to the extravillous trophoblast (EVT) lineage with HLA-G+migratory cells that invade into an extracellular matrix-based hydrogel. Compared to previous hTSC organoid methods, organoids created by this method more closely mimic the architecture of the developing human placenta and provide a novel platform to study normal and abnormal human placental development and to model exposures to pharmaceuticals, pathogens and environmental insults.MotivationHuman placental organoids have been generated to mimic physiological cell-cell interactions. However, those published models derived from human trophoblast stem cells (hTSCs) or placental villi display a non-physiologic “inside-out” morphology.In vivo, the placental villi have an outer layer of syncytialized cells that are in direct contact with maternal blood, acting as a conduit for gas and nutrient exchange, and an inner layer of progenitor, single cytotrophoblast cells that fuse to create the syncytiotrophoblast layer. Existing “inside-out” models put the cytotrophoblast cells in contact with culture media and substrate, making physiologic interactions between syncytiotrophoblast and other cells/tissues and normal and pathogenic exposures coming from maternal blood difficult to model. The goal of this study was to develop an hTSC-derived 3-D human trophoblast organoid model that positions the syncytiotrophoblast layer on the outside of the multicellular organoid.Graphical abstract
Cryo-EM structure of the CBC-ALYREF complex
Authors: Clarke Bradley P. , Angelos Alexia E. , Mei Menghan , Hill Pate S. , Xie Yihu , Ren Yi 
Published: October 2023

ABSTRACTIn eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5’ end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5’ end of mRNA. However, the molecular mechanism for CBC mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.