bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Retention and HIV Viral Suppression: A Cluster Randomised Pilot Trial of a Lay Counsellor Motivational Interviewing Training in South Africa
Authors: Onoya Dorina , Sineke Tembeka , Mokhele Idah , Vujovic Marnie , Holland Kate , Ruiter Robert A.C. 
Published: September 2024

ABSTRACTWe piloted a Motivational Interviewing (MI) training program for lay counsellors in South Africa (SA) to assess its impact on retention and viral suppression among newly diagnosed individuals living with HIV (PLHIV) at 12 months post-diagnosis. We randomized eight primary healthcare clinics (PHC) in Johannesburg to either the intervention clinics (n=4) where all lay counsellors were supported for 12 months before the PLHIV enrolment or the standard of care (n=4 clinics). Overall, 548 adults (≥ 18 years) PLHIV were recruited after HIV diagnosis from March 2020 to August 2021 (n=291 intervention, n=257 control). We conducted Poisson regression modelling to assess the intervention effect on patient attendance status (out of care – being ≥28 days late for the last appointment) and viral suppression (<50 copies/ml) at 12 months, reporting risk ratios (RR) with 95% confidence intervals (CIs). Of the 548 eligible participants enrolled, 56.3% were ≥28 days late (52.9% intervention vs 60.9% controls, RR 0.9, 95% CI: 0.7-1.0). Retention at 12 months positively correlated with baseline counselor MI skill levels (Cultivating change talk, RR 1.6, 95%CI: 1.1-2.5; Softening sustain talk, RR 1.5, 95%CI: 0.8-2.9; Empathy, RR 1.4, 95%CI: 1.0-1.8; Partnership RR 1.5, 95%CI: 1.2-1.9). Among those retained at 12 months, 65.3% of intervention participants were virally suppressed compared to 49.3% controls (RR 1.3, 95%CI: 1.0-1.7). Compared to control participants, the intervention group reported more positive counseling experiences, fewer concerns about HIV disclosure (RR 0.8 for high vs low-medium concerns, 95% CI: 0.7–1.0) and ART (RR 0.8, 95% CI: 0.7–1.0), and were more likely to express high confidence to take treatment in public (47.4% vs 28.8%, RR 1.4, 95% CI: 1.0–1.8) after counselling.
Investigating the oxidative stress-vascular brain injury axis in mild cognitive impairment of the Alzheimer type
Authors: Detcheverry Flavie E. , Senthil Sneha , Motue Winnie L.K. , Hosein Chris , Arnaoutelis Rozie , Araujo David , Fetco Dumitru , Assemlal Haz-Edine , Antel Samson , Arnold Douglas L. , Near Jamie , Schipper Hyman M. , Badhwar AmanPreet , Narayanan Sridar 
Published: September 2024

ABSTRACTINTRODUCTIONOxidative stress may contribute to brain injury in Alzheimer disease (AD) continuum. The antioxidant glutathione (GSH) can be assessed with magnetic resonance spectroscopy (MRS). Since the relationship between GSH and vascular-brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI).METHODS3T MRI/MRS data were obtained from 31 MCI participants. GSH and total N-acetylaspartate (tNAA; neuroaxonal integrity marker) were measured in posterior cingulate cortex (PCC) and frontal white matter (FWM). Cerebrovascular injury was assessed using white matter hyperintensity (WMH) volume. Global and regional brain tissue integrity were assessed using normalized brain (NBV) and hippocampal volumes.RESULTSSignificant associations were reported in FWM between GSH/total creatine (tCr) and tNAA/tCr, and between GSH and both WMH and NBV. tNAA, GSH/tCr, and tNAA/tCr were higher in PCC than FWM.DISCUSSIONOur results suggest that oxidative stress contributes to vascular-brain injury in MCI.
Caesarean myomectomy is not a risk factor for blood products transfusion among pregnant individuals with fibroids: a retrospective cohort study
Authors: Jarvi S , Aviram A , Joliffe C , Wortsman S , Liu GY , Berndl A , Barrett J , Kroft J 
Published: September 2024

ABSTRACTBackgroundUterine fibroids are common benign tumors during reproductive age. Among pregnant individuals with uterine fibroids, myomectomy at the time of cesarean delivery (CD) allows individuals to avoid a second surgery later in life.ObjectiveTo examine the safety of myomectomy performed at the time of CD and the factors that increase the risk of greater blood loss in cesarean myomectomy.Study designThis was a retrospective cohort study of all cesarean myomectomies (CM) performed at a tertiary care center in Toronto, Ontario between January 1, 2012, and June 1, 2019. The study group included individuals who had CM, and the control group included individuals with fibroids who had a CD without removing their fibroids. The primary outcome was the rate of blood products transfusion. Secondary outcomes were the need for hysterectomy and estimated blood loss (EBL). Subgroup analyses were performed for fibroid size, previous CD, and elective vs urgent CD. Logistic regression analysis was performed to assess for confounders.ResultsOverall, 110 CM were compared with 152 CD. The overall transfusion rate for CM was 7.3% compared to 0.7% in the control group (p = 0.005). All procedures requiring transfusion from both groups were performed < 370/7weeks of gestation. In logistic regression analysis, performing a myomectomy was not associated with a higher risk for transfusion. The only factors associated with transfusion were preterm birth (aOR 14.43, p=0.049) and low pre-operative hemoglobin (aOR 0.90, p=0.02). The median reported EBL was 800 mL for CM and 700 mL for controls (p<0.001). No individuals in either group required concomitant hysterectomy. Subgroup analysis showed that fibroid size ≥5cm and previous CD were not associated with increased risk of transfusion among those who had a CM, while urgent CM was significantly associated with the need for transfusion (p=0.02).ConclusionThis study demonstrates that the transfusion rate was not significantly higher in those undergoing CM at term, compared to those with fibroids undergoing CD without a myomectomy.
VAREANT: a bioinformatics application for gene variant reduction and annotation
Authors: Narayanan Rishabh , DeGroat William , Peker Elizabeth , Ahmed Zeeshan 
Published: September 2024

AbstractThe analysis of high-quality genomic variant data may offer a more complete understanding of the human genome, enabling researchers to identify novel biomarkers, stratify patients based on disease risk factors, and decipher underlying biological pathways. Although the availability of genomic data has sharply increased in recent years, the accessibility of bioinformatic tools to aid in its preparation is still lacking. Limitations with processing genomic data primarily include its large volume, associated computational and storage costs, and difficulty in identifying targeted and relevant information. Here, we presentVAREANT, an accessible and configurable bioinformatic tool to support the preparation of variant data into a usable analysis-ready format. Designed to simplify the data pre-processing workflow,VAREANTenables the curation of targeted variant datasets.VAREANTis comprised of three standalone modules: (1) Pre- processing, (2) Variant Annotation, (3) Artificial Intelligence (AI) / Machine Learning (ML) Data Preparation. Pre-processing supports the fine-grained filtering of complex variant datasets to eliminate extraneous data. Variant Annotation allows for the addition of variant metadata from public annotation databases for subsequent analysis and interpretation. AI/ML Data Preparation supports the user in creating AI/ML-ready datasets suitable for immediate analysis with minimal pre-processing required. We have successfully tested and validated our tool on numerous variable-sized datasets and implementedVAREANTin two case studies involving patients with CVDs. Efficiently extracting relevant variants into an AI/ML ready format using tools likeVAREANThas important scientific implications, such as producing targeted and high-quality datasets and helping reduce overall computational costs.
Acute Kidney Injury and Perioperative complications based on modality of nephrectomy for the treatment of kidney cancer
Authors: Patel Maulinkumar N. , Shah Deep , Patel Heli , Jaimes Edgar A. 
Published: September 2024

AbstractBackgroundNephrectomy, either partial or radical, is a key treatment for kidney cancer. The surgical approach—open, laparoscopic, or robot-assisted—can influence perioperative outcomes. This study evaluates acute kidney injury (AKI) and perioperative complications across these modalities.MethodsWe conducted a retrospective analysis using the National Inpatient Sample (NIS) of 2020–2021 to examine 12,676 kidney cancer patients who underwent nephrectomy. Patients were stratified by surgical approach: open, laparoscopic, and robot-assisted. Primary outcomes included AKI incidence, length of stay, and intra- and post-operative complications. Multivariable regression models adjusted for confounding variables, including age, sex, race, Charlson Comorbidity Index (CCI), hospital region, and teaching status.ResultsPatients undergoing open nephrectomy had the highest AKI rates, particularly for radical nephrectomy (22.13% vs. 16.52% for robotic, p < 0.001). Similarly, patients treated with open surgery had longer hospital stays and higher rates of complications, including pulmonary (7.71% vs. 4.17%, p < 0.001) and vascular (12.11% vs. 4.01%, p < 0.001) in radical nephrectomy. Multivariate analysis confirmed the increased risk of AKI and complications in open nephrectomy, with robotic-assisted surgery demonstrating the best perioperative outcomes.ConclusionOpen nephrectomy, whether partial or radical, is associated with higher AKI rates and perioperative complications compared to laparoscopic and robot-assisted surgeries. Robot-assisted nephrectomy, with its lower complication rates and shorter hospital stays, may be the preferred approach when feasible. Further efforts to expand access to minimally invasive techniques could improve outcomes for kidney cancer patients.
Erythropoietin single nucleotide polymorphisms are associated with anemia and dyslipidemia in a cardiovascular disease population
Authors: Northrup Victoria , Eadie Ashley L. , Nelson Victoria L. , D’Souza Kenneth , Hassan Ansar , Pulinilkunnil Thomas , Kienesberger Petra , Légaré Jean-Francois , Simpson Jeremy A. , Brunt Keith R. 
Published: September 2024

AbstractHuman erythropoietin (EPO) is an essential erythropoietic cytokine and recombinant biological therapeutic in anemia in chronic kidney disease. Single nucleotide polymorphisms (SNPs) in EPO have been linked to anemia and diabetic microvascular complications but no other cardiovascular comorbidities like dyslipidemia or hypertension. Here identified a clinical cohort of cardiovascular patients with anemia, dyslipidemia, hypertension, type-2 diabetes, or heart failure with preserved ejection fraction. Sanger sequencing was used for genotyping three EPO SNPs (rs1617640, rs507392 and rs551238), which were compared to clinical outcomes with SNPstat and clinical parameters profiles by student t-test. Nonstandard clinical chemistry measures of plasma EPO, hepcidin, transferrin, and ferritin were determined by ELISA. In the additive model, the C allele of rs1617640 was associated with lower EPO and anemia. In the recessive model, the SNP rs507392 genotype of GG was associated with dyslipidemia, which was associated with lower EPO in plasma and elevated total cholesterol and low-density lipoproteins. Interestingly, the G allele of rs507392 was found to be associated with hypertension, but only in females. Here we show that the SNPs in EPO are a potential risk factor for anemia, dyslipidemia, and hypertension in cardiovascular disease patients.
Depression Incidence in Patients with Hypertension in a Single Outpatient Center
Authors: Amoateng Richard , Arunthamakun Natthew , Tierliwaerdi Xiarepati , Johnston Alexandra , Gadani Mrudula 
Published: September 2024

AbstractIntroductionHypertension and depression are both highly prevalent in the United States and each condition is commonly managed in the outpatient setting. This study aims to investigate the incidence of depression in patients who are diagnosed with hypertension.MethodsA retrospective cohort study was conducted analyzing 9,240 adult patients at a single center outpatient clinic between 2019 and 2022. Blood pressure and PHQ-9 from the latest outpatient visit were recorded. Demographic data associated with hypertension were also obtained. Bivariate statistical analysis was performed. Multivariate linear and logistic regression models were adjusted for co-morbid conditions.ResultsOut of the 9,240 patients studied, 3,694 (40%) had a diagnosis of hypertension. Patients with hypertension were more likely to be older (61.96 ± 14.95 vs 39.85 ± 15.61, p=0.000), male (37% vs 33%, p =0.002) and black (45.2% vs 23.3%, p<0.001) compared with those without a diagnosis of hypertension. The mean PHQ-9 score was higher in patients with hypertension than in those without (2.97 ±4.66 vs 2.70 ± 4.93, p=0.000). Patients with hypertension were more likely to have uncontrolled depression defined as PHQ-9 score >4 (22.55% vs 19.4%, p<0.001) even when adjusted for co-morbid conditions (adj OR 1.216 95% CI 1.06 -1.34 p=0.005).ConclusionsIn this cohort of patients, a diagnosis of hypertension was associated with an increased rate of uncontrolled depressive symptoms. Hence patients with hypertension should be screened using validated PHQ-9 tools in the outpatient setting and offered appropriate treatment for depression.
Emergency admission plasma D-dimer and Prothrombin activity in acute ischemic stroke with large artery occlusion
Authors: Jiang Shandong , Guo Peizheng , Qian Cong , Yu Jun , Xu Liang , Li Xu , Chen Xianyi , Bing Fang , Yuan Yuan , Tan Zhongju , Xu Jing , Li Jianru 
Published: September 2024

ABSTRACTBackgroundThe coagulation system is intrinsically linked to pathological mechanism and progression of ischemic stroke. However, the role of preoperative coagulation function in determining the functional outcomes of acute ischemic stroke patients following large artery occlusion (AIS-LVO) has not been extensively evaluated in peer-reviewed literature.MethodsWe utilized logistic regression analyses, complemented by the construction of receiver operating characteristic (ROC) curves, to identify significant predictive factors for poor prognosis following EVT. Additionally, subgroup analyses were conducted to further assess the prognostic efficacy of coagulation function across different subgroups.ResultsA total of 607 patients were enrolled, with 335 (55.19%) experiencing an unfavorable outcome. Multivariate regression analysis identified preoperative D-dimer and PTA as independent predictors of 3-month prognosis. After adjusting for confounders, elevated preoperative D-dimer levels (≥715 mg/L), identified by cut-off value, were a significant predictor of poor prognosis, with 2.51-fold higher risk compared to the normal range. Conversely, elevated PTA levels (≥85.5%) were significantly and inversely associated with poor prognosis, indicating a reduced risk of 0.39 times. Furthermore, the combination of elevated D-dimer and reduced PTA demonstrated a synergistic effect, markedly increasing the risk of poor outcomes in AIS-LVO patients. Subgroup analyses revealed that failed recanalization, comorbid diabetes, and non-middle cerebral artery (MCA) occlusion significantly influence the predictive value of D-dimer and PTA for clinical outcomes.ConclusionElevated admission D-dimer and reduced PTA levels are an independent predictor of poor prognosis in patients with AIS-LVO, and there is a synergistic interaction between the two variables.
Naturally acquired IgG responses toPlasmodium falciparumdo not target the conserved termini of the malaria vaccine candidate merozoite surface protein 2
Authors: Zerebinski Julia , Margerie Lucille , Han Nan Sophia , Moll Maximilian , Ritvos Matias , Jahnmatz Peter , Ahlborg Niklas , Ngasala Billy , Rooth Ingegärd , Sjöberg Ronald , Sundling Christopher , Yman Victor , Färnert Anna , Plaza David 
Published: September 2024

AbstractMalaria remains a significant burden, and a fully protective vaccine againstPlasmodium falciparumis critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen merozoite surface protein 2 (MSP2) are associated with protection fromP. falciparummalaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to more easily study the genetic diversity and immune responses towards antigens from clinical isolates. This study sought to better understand naturally acquired MSP2-specific antibody responses. IgG responses against recombinantly expressed full- length, central polymorphic regions, and peptides derived from the conserved termini of MSP2 variants sequenced from patient isolates, were tested in plasma from travelers with recent, acute malaria and from individuals living in an endemic area of Tanzania. IgG responses towards full MSP2 and truncated MSP2 antigens were variant specific. IgG antibodies in the plasma of first-time infected or previously exposed travelers did not recognize the conserved termini of expressed MSP2 variants by ELISA, but they bound 13- amino acid long linear epitopes from the termini in a custom-made peptide array. Alphafold3 modelling suggests extensive structural heterogeneity in the conserved termini upon antigen oligomerization. IgG from individuals living in an endemic region, many who were asymptomatically infected, did not recognize the conserved termini by ELISA. Our results suggest that responses to the variable regions are important for the development of naturally acquired immunity towards MSP2.
Calcium dynamics of skin-resident macrophages during homeostasis and tissue injury
Authors: Guerrero Pearl A. Leon , Rasmussen Jeffrey P. , Peterman Eric 
Published: September 2024

ABSTRACTImmune cells depend on rapid changes in intracellular calcium activity to modulate cell function. Skin contains diverse immune cell types and is critically dependent on calcium signaling for homeostasis and repair, yet the dynamics and functions of calcium in skin immune cells remain poorly understood. Here, we characterize calcium activity in Langerhans cells, skin-resident macrophages responsible for surveillance and clearance of cellular debris after tissue damage. Langerhans cells reside in the epidermis and extend dynamic dendrites in close proximity to adjacent keratinocytes and somatosensory peripheral axons. We find that homeostatic Langerhans cells exhibit spontaneous and transient changes in calcium activity, with calcium flux occurring primarily in the cell body and rarely in the dendrites. Triggering somatosensory axon degeneration increases the frequency of calcium activity in Langerhans cell dendrites. By contrast, we show that Langerhans cells exhibit a sustained increase in intracellular calcium following engulfment of damaged keratinocytes. Altering intracellular calcium activity leads to a decrease in engulfment efficiency of keratinocyte debris. Our findings demonstrate that Langerhans cells exhibit context-specific changes in calcium activity and highlight the utility of skin as an accessible model for imaging calcium dynamics in tissue-resident macrophages.SIGNIFICANCE STATEMENTCalcium activity in immune cells is thought to regulate cell function, but studies focusing on tissue-resident macrophages are limited.Skin-resident macrophages known as Langerhans cells exhibit rapid and transient changes in calcium activity in homeostatic conditions, which can change depending on the type of tissue injury inflicted. Pharmacological perturbation of calcium activity leads to a decrease in Langerhans cell engulfment.These findings suggest calcium activity is important for tissue surveillance by Langerhans cells.
Expansionin situgenome sequencing links nuclear abnormalities to hotspots of aberrant euchromatin repression
Authors: Labade Ajay S. , Chiang Zachary D. , Comenho Caroline , Reginato Paul L. , Payne Andrew C. , Earl Andrew S. , Shrestha Rojesh , Duarte Fabiana M. , Habibi Ehsan , Zhang Ruochi , Church George M. , Boyden Edward S. , Chen Fei , Buenrostro Jason D. 
Published: September 2024

AbstractMicroscopy and genomics are both used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. While emerging multiplexed imaging methods can simultaneously localize genomic regions and nuclear proteins, their ability to accurately measure DNA-protein interactions is constrained by the diffraction limit of optical microscopy. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. We applied ExIGS to fibroblast cells derived from an individual with Hutchinson-Gilford progeria syndrome to characterize how variation in nuclear morphology affects spatial chromatin organization. Using this data, we discovered that lamin abnormalities are linked to hotspots of aberrant euchromatin repression that may erode cell identity. Further, we show that lamin abnormalities heterogeneously increase the repressive environment of the nucleus in tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform for connecting nuclear abnormalities to changes in gene regulation across disease contexts.
Integration of light quality signals regulates ABA abundance and stomatal movements during seedling establishment
Authors: Gustavsson Mathilda , Hill Lionel , Franklin Keara A. , Pridgeon Ashley J. 
Published: September 2024

AbstractObtaining sufficient light for photosynthesis and avoiding desiccation are two key challenges faced by seedlings during early establishment. Perception of light quality via specialised photoreceptors signals the availability of sunlight for photosynthesis. Canopy shade is depleted in red (R) and enriched in far-red (FR) light, lowering R:FR ratio, while direct sunlight and sunflecks contain UV-B. The balance of these wavelengths can determine the developmental strategy adopted by seedlings to either avoid shade, via stem elongation, or promote the expansion of photosynthetic organs. How seedlings regulate stomatal movements in different light environments is poorly understood. Using FR and UV-B supplementation to mimic aspects of canopy shade and sunlight respectively, we monitored stomatal apertures inArabidopsis thalianacotyledons. We show that low R:FR inhibits stomatal opening via a mechanism involving PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and increased abscisic acid (ABA). In contrast, UV-B perceived by the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor antagonises this response to promote stomatal opening in a response requiring phototropin photoreceptors. The convergence of phytochrome and UVR8 signalling to control ABA abundance enables plants to coordinate stem elongation and water use during seedling establishment in dynamic light environments.