bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary efficacy of a community health worker homebased intervention for the control and management of hypertension in Kiambu County, Kenya- A randomized control trial
Authors: Mbuthia Grace Wambura , Mwangi James , Magutah Karani , Oguta James Odhiambo , Ngure Kenneth , McGarvey Stephen T. 
Published: October 2023

AbstractIn Sub Saharan Africa, there is a growing burden of non-communicable diseases, which poses a big challenge to the weak health system in these resource-limited settings. The aim of this study was to determine the feasibility and preliminary efficacy of a community health workers (CHW) home-based lifestyle interventions to improve blood pressure (BP) control and body composition among hypertensive patients in low-income populations of Kiambu County, Kenya. This was a randomized controlled trial (RCT) involving 80 patients with uncontrolled high BP (systolic BP (SBP) ≥140mmHg and/or diastolic BP (DBP) ≥90) randomized to either a CHW homebased intervention or a usual care (control) arm and followed up for 6 months. The intervention involved monthly CHW home-visits for health education and audits on behavioral risk factors that affect BP. An adapted WHO stepwise questionnaire and international physical activity questionnaire was used to collect data on behavioral cardiovascular risk factors. To assess the main outcomes of BP, body mass index (BMI) and waist-height-ratio (WHtR), a survey was conducted at baseline, 3 months, and 6 months. Data regarding univariate, bivariate and multivariate (repeated measurements between and within groups) analysis at 5% level of significance were analyzed using STATA 18. Generalized estimating equations (GEE) for repeated measures were used to estimate changes in BP, BMI and WHtR, and to examine the association between the CHW intervention and BP control. The study revealed that 77.5% and 92.5% of the participants in usual care and intervention groups completed the follow-up, respectively. After 6 months of follow-up, there was a reduction in the mean SBP and DBP for both arms, and reductions in BMI and WHtR only in the intervention arm. The adjusted mean reduction in SBP (-8.4 mm Hg; 95% CI, -13.4 to -3.3; P=0.001) and DBP (-5.2 mm Hg 95% CI, -8.3 to -2.0; P<0.001) were significantly higher in the intervention group compared to the control group. The proportion of participants who achieved the controlled BP target of <140/90 mm Hg was 62.2% and 25.8% for the intervention and usual care arm, respectively. The proportion with controlled BP was significantly higher in the intervention arm compared to the usual care arm after adjusting for baseline covariates (AOR 2.8, 95% CI 1.3-6.0, p=0.008). There was no significant effect of the intervention on BMI and WHtR. In conclusion, a home-based CHW intervention was significantly associated with reduction in BP among hypertensive patients compared to usual care. Future fully powered RCTs to test the effectiveness of such interventions among low-income populations are recommended.
Comprehensive single cell aging atlas of mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer
Authors: Angarola Brittany L. , Sharma Siddhartha , Katiyar Neerja , Kang Hyeon Gu , Nehar-Belaid Djamel , Park SungHee , Gott Rachel , Eryilmaz Giray N. , LaBarge Mark A. , Palucka Karolina , Chuang Jeffrey H. , Korstanje Ron , Ucar Duygu , Anczukow Olga 
Published: October 2023

AbstractAging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. We investigate how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory, or cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk+, memory CD4+, γδ) and M2-like macrophages expand with age. Spatial transcriptomics reveal co-localization of aged immune and epithelial cellsin situ. Lastly, transcriptional signatures of aging mammary cells are found in human breast tumors, suggesting mechanistic links between aging and cancer. Together, these data uncover that epithelial, immune, and stromal cells shift in proportions and cell identity, potentially impacting cell plasticity, aged microenvironment, and neoplasia risk.
Discovery of a locus associated with susceptibility to esca dieback in grapevine
Authors: Guillaume Arnold , Emilce Prado , Vincent Dumas , Gisèle Butterlin , Eric Duchêne , Komlan Avia , Didier Merdinoglu 
Published: October 2023

AbstractEsca is the most destructive and predominant grapevine trunk diseases. The chronic infections and vine mortality caused by esca syndrome lead to huge economic losses and threatens the sustainability of vineyards worldwide. Although shown as associated with the presence of wood fungi, the etiology of esca remains still unclear and putatively involves multifactorial causes, which makes the development of effective control methods challenging. As differences in esca susceptibility had already been observed among grapevine varieties, we investigated in a biparental population the presence of genetic factors that can explain theses variations. Thanks to the destructive phenotyping of a 16-year-old vineyard plot, we discovered that the Gewurztraminer variety carries on chromosome 1 a locus linked to variations in trunk necrosis associated with esca, which we have namedENS1. Our study also suggests that there is a partial link between trunk vigor and necrosis due to esca. To our best knowledge,ENS1is the first instance of genetic factor identified as involved in the limitation of necrosis associated to grapevine esca. While the identification ofENS1alone may not provide a complete resolution of the esca issue, this discovery represents nonetheless a first step towards a genetic solution and paves the way for broader genetic investigations in the future.
Support Vector Machine based prediction models for drug repurposing and designing novel drugs for colorectal cancer
Authors: Sengupta Avik , Kumar Rahul 
Published: October 2023

AbstractColorectal cancer (CRC) has witnessed a concerning increase in incidence and poses a significant therapeutic challenge due to its poor prognosis. There is a pressing demand to identify novel drug therapies to combat CRC. In this study, we addressed this need by utilizing the library of CRC pharmacological profiles of anticancer drugs and developed QSAR models for prediction of alternative and promiscuous anti-cancer compounds for CRC treatment. Our QSAR models demonstrated their robustness by achieving high correlation of determination (R2) after 10-fold cross validation. For 12 CRC cell lines, R2ranges from 0.609-0.827. Highest performance was achieved for SW1417 and GP5d cell lines with R2, 0.827 and 0.786, respectively. Further, we listed the most common descriptors in the drug profiles of the CRC cell lines and we also checked the correlation of the descriptors with the drug activity. The KRFP314 fingerprint was the predominantly occurring descriptor, with the KRFPC314 fingerprint following closely in prevalence within the drug profiles of the CRC cell lines. Beyond predictive modeling, we also successfully validated drug-to-oncogene relationship viain-silicomethods and identified FDA-approved drugs which could be used as potential anti-CRC drugs, paving the way for subsequentin vitroorin vivoexperiments to validate their efficacy. To provide easy accessibility and utility of our research findings, we have incorporated these models into a free-to-use user-friendly prediction webserver named, “ColoRecPred” hosted on project.iith.ac.in/cgntlab/colorecpred. This web-based tool can be used to screen for potential anti-cancer compounds for CRC.
LAVASET: Latent Variable Stochastic Ensemble of Trees. A novel ensemble method for correlated datasets
Authors: Kasapi Melpomeni , Xu Kexin , Ebbels Timothy M.D. , O’Regan Declan P. , Ware James S. , Posma Joram M. 
Published: October 2023

MotivationRandom Forests (RFs) can deal with a large number of variables, achieve reasonable prediction scores, and yield highly interpretable feature importance values. As such, RFs are appropriate models for feature selection and further dimension reduction (DR). However, RFs are often not appropriate for correlated datasets due to their mode of selecting individual features for splitting. Addressing correlation relationships in high dimensional datasets is imperative for reducing the number of variables that are assigned high importance, hence making the DR most efficient. Here, we propose the LAtent VAriable Stochastic Ensemble of Trees (LAVASET) method that derives latent variables based on the distance characteristics of each feature and aims to incorporate the correlation factor in the splitting step.ResultsWithout compromising on performance in the majority of examples, LAVASET outperforms RF by accurately determining feature importance across all correlated variables and ensuring proper distribution of importance values. LAVASET yields mostly non-inferior prediction accuracies to traditional RFs when tested in simulated and real 1D datasets, as well as more complex and high-dimensional 3D datatypes. Unlike traditional RFs, LAVASET is unaffected by single ‘important’ noisy features (false positives), as it considers the local neighbourhood. LAVASET, therefore, highlights neighbourhoods of features, reflecting real signals that collectively impact the model’s predictive ability.LAVASET is freely available as a standalone package fromhttps://github.com/melkasapi/LAVASET.
Effect of Soybean and Seaweed-based Diets on Growth Performance, Feed Utilization, and Gut Microbiota of Tilapia: A Systematic Review and Meta-analysis
Authors: Viagem Leonildo dos Anjo , Hakizimana Jean Nepomuscene , Rumisha Cyrus , Cerozi Brunno da Silva , Misinzo Gerald 
Published: October 2023

AbstractTilapia, a significant aquaculture species globally, relies heavily on feed for its production. While numerous studies have investigated the impact of soybean and seaweed-based diets on tilapia, a comprehensive understanding remains elusive. This review aimed at evaluating and synthesizing the existing literature on these diets’ effects, focusing on growth performance, feed utilization, and gut microbiota. A systematic search of databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a total of 57 studies were included in the qualitative analysis and 24 in the meta-analysis. The results indicated that soybean-based diets, at a 59.4% inclusion level improved the Specific Growth Rate (SGR) of tilapia with an effect size of -2.14 (95% CI: -2.92, -1.37;p< 0.00001;I2= 99%) and did not improve the feed conversion rate (FCR), as the effect size was 1.80 (95% CI: 0.72, 2.89;p= 0.001;I2= 100%). For seaweed-based diets, at a 15,9% inclusion level did not improve SGR, with an effect size of -0.74 (95% CI: -1.70, 0.22;p= 0.13;I2= 99%), and the FCR with an effect size of -0.70 (95% CI: -1.94, 0.54;p= 0.27;I2= 100%). Regarding the gut microbiota, was noted a lack of studies meeting the inclusion criteria for tilapia. However, findings from studies on other farmed fishes suggested that soybean and seaweed-based diets could have diverse effects on gut microbiota composition and promote the growth of beneficial microbiota. This study suggests that incorporating soybean-based diets at 59.4% inclusion can improve the SGR of tilapia. Seaweed-based diets, while not demonstrating improvement in the analyzed parameters with an inclusion level of 15.9%, have the potential to contribute to the sustainability of the aquaculture industry when incorporated at lower levels.
C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity
Authors: Morin Cécile , Faure Flora , Guenoun David , Sautet Irvin , Diao Sihao , Faivre Valérie , Hua Jennifer , Schwendimann Leslie , Mokhtari Amazigh , Martin Rebeca , Chadi Sead , Demené Charlie , Delahaye-Duriez Andrée , Diaz-Heijtz Rochellys , Fleiss Bobbi , Matrot Boris , Auger Sandrine , Tanter Mickael , Van Steenwinckel Juliette , Gressens Pierre , Bokobza Cindy 
Published: October 2023

AbstractInfants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis (Dammann, O. and Leviton, A.,Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res, 2014.75(3): p. 376-80). In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery (Luca, A.,et al.,Birth trauma in preterm spontaneous vaginal and cesarean section deliveries: A 10-years retrospective study.PloS one,2022, 17(10), e0275726.) We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation (Favrais, G.,et al.,Systemic inflammation disrupts the developmental program of white matter.Ann Neurol,2011.70(4): p. 550-65). This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.Significance StatementIn a well-established mouse model of the encephalopathy of prematurity, we observed that C-section exacerbates the deleterious effects of neonatal systemic inflammation (intraperitoneal injections of IL-1β between postnatal days one and five) on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced brain functional connectivity. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.
Identification of NanoLuciferase Substrates Transported by Human ABCB1 and ABCG2 and their Zebrafish Homologs at the Blood-Brain Barrier
Authors: Inglut Collin T. , Quinlan John A. , Robey Robert W. , Thomas Joanna R. , Walker Joel R. , Zhou Wenhui , Huang Huang-Chiao , Gottesman Michael M. 
Published: October 2023

AbstractATP-binding cassette (ABC) transporters expressed at the blood-brain barrier (BBB) impede delivery of therapeutic agents to the brain, including agents to treat neurodegenerative diseases and primary and metastatic brain cancers. Two transporters, P-glycoprotein (P-gp, ABCB1) and ABCG2, are highly expressed at the BBB and are responsible for the efflux of numerous clinically useful chemotherapeutic agents, including irinotecan, paclitaxel, and doxorubicin. Based on a previous mouse model, we have generated transgenic zebrafish in which expression of NanoLuciferase (NanoLuc) is controlled by the promoter of glial fibrillary acidic protein, leading to expression in zebrafish glia. To identify agents that disrupt the BBB, including inhibitors of ABCB1 and ABCG2, we identified NanoLuc substrates that are also transported by P-gp, ABCG2, and their zebrafish homologs. These substrates will elevate the amount of bioluminescent light produced in the transgenic zebrafish with BBB disruption. We transfected HEK293 cells with NanoLuc and either human ABCB1, ABCG2, or their zebrafish homologs Abcb4 or Abcg2a, respectively, and expressed at the zebrafish BBB. We evaluated the luminescence of ten NanoLuc substrates, then screened the eight brightest to determine which are most efficiently effluxed by the ABC transporters. We identified one substrate efficiently pumped out by ABCB1, two by Abcb4, six by ABCG2, and four by Abcg2a. These data will aid in the development of a transgenic zebrafish model of the BBB to identify novel BBB disruptors and should prove useful in the development of other animal models that use NanoLuc as a reporter.Significance StatementThe ATP-Binding Cassette (ABC) transporters ABCB1 and ABCG2 at the blood-brain barrier (BBB) hinder pharmacological treatment of brain-related diseases. Consequently, there is a need for tools to identify BBB disruptors. We conducted a screen of ten NanoLuciferase substrates, identifying the brightest and those that were transported by human and zebrafish ABC transporters at the BBB. This work supports and complements our development of a transgenic zebrafish model, in which NanoLuciferase is expressed within glial cells, enabling detection of BBB disruption.
Insect Pollinators: The Time is Now for Identifying Species of Greatest Conservation Need
Authors: deMaynadier Phillip , Schlesinger Matthew D. , Hardy Spencer P. , McFarland Kent P. , Saucier Laura , White Erin L. , Zarrillo Tracy A. , Young Bruce E. 
Published: October 2023

ABSTRACTSevere declines in the abundance of insects, including economically and ecologically important pollinators are alarming conservationists and the public. Yet despite these increasingly well documented declines, relatively few pollinating insects other than some butterflies and bumble bees have appeared as Species of Greatest Conservation Need (SGCN) in State Wildlife Action Plans, decadal-scale blueprints for wildlife conservation efforts across the United States that require updating in 2025. Species absent from SGCN lists are ineligible for congressionally appropriated State Wildlife Grants that direct millions of dollars annually for their conservation. In the past, knowledge about the distribution and abundance of many insect pollinators was too poor to identify those meeting state guidelines for inclusion as SGCN. Using case studies from 4 northeastern states, we demonstrate that sufficient conservation status data now exists for many pollinators, including bees, butterflies, moths, beetles, and flower flies, to identify at-risk species meriting inclusion on SGCN lists in many states. Doing so will increase funding available for surveys, habitat protection and enhancement, and other conservation activities that will benefit this vitally important guild.
Origins and Evolution of NovelBacteroidesin Captive Apes
Authors: Nishida Alexandra H. , Ochman Howard 
Published: October 2023

AbstractBacterial strains evolve in response to the gut environment of their hosts, with genomic changes that influence their interactions with hosts as well as with other members of the gut community. Great apes in captivity have acquired strains ofBacteroides xylanisolvens, which are common within gut microbiome of humans but not typically found other apes, thereby enabling characterization of strain evolution following colonization. Here, we isolate, sequence and reconstruct the history of gene gain and loss events in numerous captive-ape-associated strains since their divergence from their closest human-associated strains. We show that multiple captive-ape-associatedB. xylanisolvenslineages have independently acquired gene complexes that encode functions related to host mucin metabolism. Our results support the finding of high genome fluidity inBacteroides, in that several strains, in moving from humans to captive apes, have rapidly gained large genomic regions that augment metabolic properties not previously present in their relatives.Significance statementChronicling the changes that occur in bacterial genomes after a host-switch event is normally difficult due to age of most bacteria-host associations, which renders uncertainties about the bacterial ancestor (and ancestral genome) prior to colonization of the new host. However, the gut microbiomes of great apes in captivity contain bacterial strains that are unique to humans, allowing fine-scale assessment and reconstruction of the genomic changes that follow colonization. By sequencing and comparing closely related strains ofBacteroidesthat are restricted both to human and to captive great apes, we found that multiple bacterial lineages convergently acquired sets of genes involved in the metabolism of dietary polysaccharides. These results show that over relatively short timescales, the incorporation of strains into microbiomes involves large-scale genomic events that correspond to characteristics of the new host environment.
Experimental exposure to winter thaws reveals tipping point in yellow birch bud mortality and phenology in the northern temperate forest of Québec, Canada
Authors: Marquis Benjamin , Lajoie Geneviève 
Published: October 2023

AbstractClimate change is expected to increase the frequency and intensity of winter thaws, which could have two contrasting effects on leaf phenology. Phenology could either be advanced through the acceleration of forcing accumulation or chilling completion, or be postponed through a reduction in chilling associated with warming air temperature. We tested the influence of winter thaws on budburst phenology by exposing 300 tree cuttings of sugar maple and yellow birch trees to five different frequencies and durations of winter thaws in the lab. In spring, half of the cuttings were exposed to air temperature in two cities representing an air temperature gradient of + 2.0 °C to mimic the ongoing climate warming and bud phenology was monitored three times a week. Irrespective of thaw treatment, yellow birch phenology occurred earlier in the warmer city, showing the importance of spring temperature in triggering budburst. The treatment with the highest frequency and duration of thawing increased bud mortality and delayed the onset of spring phenology whereas low frequency treatments did not, thereby identifying a tipping point in the impact of winter thaws on bud phenology. Past this point, winter thaws could slow the acceleration of bud phenology induced by warmer spring temperature and limit carbon uptake by delaying the closure of the canopy. Climate change simulations projected by the CMIP6 Canadian downscaled climate scenario show that winter thaws will increase in frequency. Hence the expected advance in the spring phenology associated with warmer spring is not necessarily as straightforward as previously thought.Graphical abstract