bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary healthcare providers’ perspectives on six-month dispensing of HIV medication in South Africa: a cross-sectional survey
Authors: Ntjikelane Vinolia , Huber Amy , Morgan Allison , Pascoe Sophie , Manganye Musa , Malala Lufuno , Rosen Sydney 
Published: January 2025

AbstractBackgroundIn many African countries the dispensing duration for antiretroviral therapy (ART) medication for HIV treatment has increased from 3 months to 6 months for stable clients. To help inform a decision about whether to move from three-month dispensing (3MMD) to six-month dispensing (6MMD) in South Africa, we surveyed healthcare providers about their perspectives on dispensing and scripting durations.MethodsWe conducted a cross-sectional survey of healthcare providers (nurses, managers, pharmacists) at 24 primary healthcare clinics in South Africa from May to September 2024, asking closed- and open-ended questions. Results are reported as frequencies.Results182 providers were enrolled from four provinces (median age 44, 88% female). Most (>70%) respondents said that the 3MMD guideline offered multiple benefits for providers and patients, compared to the previous two-month dispensing rule; most (64%) also said there were no challenges in implementing 3MMD. >80% of respondents across all cadres reported that they would be comfortable dispensing 6 months of ART at a time, believing that it would reduce facility overcrowding, lighten staff workloads, and be advantageous to clients by decreasing their visit burden and travel costs. Two thirds (63%) of participating nurses, who provide the largest share of direct ART care, were also in favour of resuming 12-month scripting for ART; the remaining 37% expressed concerns about decreases in treatment adherence and clinical monitoring of clients.ConclusionMost healthcare providers at primary healthcare clinics in South Africa are in favour of allowing six-month dispensing and 12-month prescriptions as options for established ART clients.
Single-Cell Temporal Atlas of Myeloid Cells in the Live Haemorrhagic Brain
Authors: Kawamura Yuki , Johnson Conor W. , DeLong Jonathan , de Lima Camillo Lucas Paulo , Takahashi Munetomo , Beatty Hannah E. , Herbert Ryan , Cord Branden J. , Matouk Charles , Askenase Michael , Sansing Lauren H. 
Published: January 2025

AbstractCNS-resident microglia and recruited myeloid cells populate the haematoma in intracerebral haemorrhage (ICH), but the contribution of these cell populations to injury and repair has been controversial. To better characterise myeloid cell changes over time, we employed single-cell RNA sequencing to generate a unique paired dataset of live haematoma and peripheral blood samples from 10 ICH patients. This work presents a temporal atlas of ICH myeloid populations and identifies population-specificin-situtranscriptional drivers. In addition to distinct populations of activated microglia and TNF-low microglia, we found a unique and highly activated population of CD14+monocytes in the haematoma. Perturbation analysis comparing haematoma-associated monocytes to shared populations in blood and haematomas identified TNF signalling as the primary driver of their activation. Employing a custom temporal trajectory analysis based on the embeddings of a single-cell foundation model, we found that this TNF response in monocytes was transient, peaking early after haemorrhage and decreasing over the ensuing 48 hours. Our analysis further identified a transient population of highly activated microglia as the likely source of TNF during the acute stage of ICH. Acute TNF signalling in CD14+monocytes associated with better adjusted outcomes both in our and external cohorts. Overall, our results suggest that acute TNF signalling between transient populations of activated microglia and unique haematoma-associated monocytes could potentially be beneficial in recovery after ICH.One sentence summaryWe present a single-cell temporal atlas of myeloid cells in intracerebral haemorrhage and identify TNF signalling as a driver of haematoma dynamics.
Cardiometabolic biomarkers and systemic inflammation in US adolescents and young adults with latent tuberculosis infection: a population-based cohort study
Authors: Magodoro IM , Ntusi NAB , Jao J , Heather JZ , Claggett BL , Siedner MJ , Wilkinson KA , Wilkinson RJ 
Published: January 2025

AbstractBackgroundMycobacterium tuberculosis(M.tb) infection in adults increases incident type 2 diabetes and atherosclerotic cardiovascular disease risk, but it is unknown if this cardiometabolic detriment occurs in the young. We sought to determine if young persons with latent tuberculosis infection (LTBI) have worse cardiometabolic health than their tuberculosis (TB) uninfected peers.MethodsPeripubescent adolescents (12-15 years old) and older adolescents and young adults (16-30 years old) (older participants) were cross-sectionally surveyed. LTBI was assessed by tuberculin skin testing (induration ≥10mm). Fasting plasma glucose (FPG), HbA1c, c-peptide, NTproBNP, hs-Troponin T, c-reactive protein (CRP), ferritin, diabetes/prediabetes (FPG ≥5.6 mmol/L and/or HbA1c ≥5.7%) and homeostatic model of insulin resistance (IR) (HOMA2-IR) were measured as study outcomes. LTBI cases were propensity score matched 1:4 on sociodemographic and lifestyle indicators with TB uninfected controls to estimate adjusted median (adjMedian), mean differences (adjMD), and odds ratios (adjOR) of cardiometabolic indices.ResultsSeventy-five young persons with LTBI were matched with 300 TB uninfected peers of similar age [mean (SD): 18.3 (5.5) vs. 18.0 (5.5) years], race [Hispanic: 74.7% vs. 76.7%], and sedentary time [3.5 (1.5%) vs. 3.5 (1.6) hours/day]. LTBI was associated with higher inflammation [adjMedian (IQR) CRP: 0.22 (0.05, 0.34) vs. 0.11 (0.04, 0.35) mg/dL; p=0.027; ferritin: 55.0 (25.1, 90.3) vs. 41.1 (29.5, 136.2) ng/mL; p=0.047] among older participants, but not peripubescent adolescents [CRP: 0.08 (0.04, 0.36) vs. 0.05 (0.02, 0.17) mg/dL; p=0.42; ferritin: 23.0 (18.5, 33.5) vs. 32.7 (21.5, 48.2) ng/mL; p=0.011]. By contrast, there were no meaningful differences in FPG [adjMD (95%CI): −0.05 (−0.22, 0.12) mmol/L; p=0.57], HbA1c [0.0 (−0.17, 0.17) %; p=0.98] or diabetes/prediabetes prevalence [adjOR (95%CI): 0.9 (0.29, 2.29); p=0.85] by LTBI status. Insulin secretion and resistance, NTproBNP and hs-Troponin T were also similar.ConclusionOlder adolescents and young adults with LTBI had greater markers of inflammation than those without LTBI while cardiometabolic profiles were similar across TB and/or age strata. Unlike in adults,M.tbinfection in young persons does not appear associated with cardiometabolic derangement, although longterm consequences of chronic inflammation requires further study.
Cytotoxic activity against human leukemia cells of Kaempferol-3-O-rhamnoside from VietnameseSchima wallichii(DC.) Korth: A combination ofin vitroandin silicoinsights
Authors: Tran Manh Hung , Nguyen Yen Nhi , Pham Lam Thuy Mi , Tran Thuy Linh Thi , Nguyen Tan Khanh , Le Tuan Anh , Bich Van Ngo Thai , Truong Hieu Phu Chi , Tran Vinh Pham Phu 
Published: January 2025

AbstractIn the investigation of the cytotoxic activity against leukemia cells of Vietnamese medicinal plants, we identified the extract ofSchima wallichii(DC.) Korth as capable of inhibiting several leukemia cell lines. In this study, we isolated a main compound as kaempferol-3-O-rhamnoside, marking the first report of this compound being isolated from the stem ofSchima wallichiicollected in Vietnam. Inin vitroexperiments, kaempferol-3-O-rhamnoside exhibited cytotoxic effects on three leukemia cell lines, HL-60 and KG-1. Regarding its mechanism of action, the compound effectively inhibited growth of HL-60 and KG-1 leukemia cell lines by activating caspase-3 and caspase-9 in both cell lines. Additionally, kaempferol-3-O-rhamnoside upregulated the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2 in these cell lines.In silicoexperiments revealed that docking simulations showed kaempferol-3-O-rhamnoside binds to both the allosteric site of procaspase-3 and the active site of PARP1, with binding energies of -7.36 and -10.76 kcal/mol, respectively. Kaempferol-3-O-rhamnoside demonstrated stable binding affinity with PARP1, characterized by significant hydrogen bonding, hydrophobic interactions, and pi-stacking in the molecular dynamic simulations. These results suggest that kaempferol-3-O-rhamnoside has the potential PARP1 inhibitor, making it a promising candidate for targeting leukemia cells. Moreover, it provides evidence for considering this compound in drug discovery and development targeting PARP1-related pathways.
A 3D ovarian cancer metastasis model using a decellularized peritoneal matrix to study therapy response
Authors: Gjerde Christiane Helgestad , Kleinmanns Katrin , Langer Anika , Ponce Gorka Ruiz de Garibay , Rozmus Ezekiel , Stangeland Gina Nyhus , Leitch Calum , Elnour Rammah , Dongre Harsh Nitin , Berger Constantin , Gultekin Okan , Forcados Christopher , Stensland Maria , Nyman Tuula A. , Lehti Kaisa , Davidson Ben , Wälchli Sébastien , Gelebart Pascal , Costea Daniela Elena , Kotopoulis Spiros , Bjørge Line , McCormack Emmet 
Published: January 2025

AbstractHigh-grade serous ovarian carcinoma (HGSOC) presents a significant therapeutic challenge. Late-stage disease is frequently associated with peritoneal carcinomatosis. The peritoneal metastases exhibit a unique tumor microenvironment (TME) distinct from the primary tumors and other metastatic sites. Understanding the critical influence of the extracellular matrix (ECM) in shaping the tumor phenotype is essential for the development of effective new therapies. This study introduces a novel three-dimensional (3D) model of HGSOC peritoneal metastases using a porcine decellularized peritoneal-derived ECM scaffold, referred to as peritoneal matrix (PerMa). We show that the decellularization maintains the structural integrity and composition of ECM molecules. Comparative analysis reveals structural, compositional, and mechanical similarities between porcine and human peritoneal matrices, underscoring the porcine model’s translational relevance for modeling human peritoneum physiology. The PerMa supports the 3D growth of HGSOC cell lines. The model enables the assessment of sensitivity to traditional chemotherapy and novel cell-based immunotherapy through confocal imaging and quantification of cell volume. Our model offers a valuable platform for investigating peritoneal carcinomatosis in HGSOC, with the potential to contribute significantly to the development of novel therapeutic approaches.
Optimal Graph Representations and Neural Networks for Seizure Detection Using Intracranial EEG Data
Authors: Díaz-Montiel Alan A. , Zhang Richard , Lankarany Milad 
Published: January 2025

AbstractIn recent years, several machine-learning (ML) solutions have been proposed to solve the problems of seizure detection, seizure characterization, seizure prediction, and seizure onset zone (SOZ) localization, achieving excellent performance with accuracy levels above 95%. However, none of these solutions has been fully deployed in clinical settings. The primary reason has been a lack of trust from clinicians towards the so-called black-box decision-making operability of ML. More recently, research efforts have focused on explainability frameworks of ML models that are clinician-friendly. In this paper, we conducted an analysis of graph neural networks (GNN), a paradigm of artificial neural networks optimized to operate on graph-structured data, as a framework to detect seizures from intracranial electroencephalographic (iEEG) data. We employed two multi-center international datasets, comprising 23 and 16 patients and 5 and 7 hours of iEEG recordings. We evaluated four GNN models, with the highest performance achieving a seizure detection accuracy of 97%, demonstrating its potential for clinical application.
Evolutionary conserved reciprocal senescence and tumor suppressor signals limit lifetime cancer
Authors: Liu Liqiong , Davis Stephani , Yusuff Shamila , Strange Ann , Zhuang Yonghua , Vaddi Prasanna , Flaherty Kathleen , Jara Kelly , Kramer Joseph , Archer Christine , Lee Schuyler , Gao Bifeng , Van Bokhoven Adrie , Wang Wei , Pine Sharon R. , Nakamura Tetsuya , Sabaawy Hatim E. 
Published: January 2025

AbstractCellular senescence features a durable exit from the cell cycle triggered by stress or carcinogens. The INK4 locus is inactivated in various cancers, yet in senescence, p16Ink4ais activated. Whether senescence is tumor-suppressing or -promoting remains a conundrum. We discovered an evolutionally-conserved Vertebrata INK4-homolog. Thisink4abtriggers senescence upon oxidative- and/or carcinogenic-stress. Adult Ink4ab-deficient animals failed to activate senescence and developed spontaneous cancers. Combined Ink4ab and Tp53 deficiency revealed a reciprocal senescence and apoptosis regulation, controlling tumorigenesis, including retinoblastoma. INK4-hematopoietic-deficient mice exhibited p19Arf-dependent enhanced senescence-like phenotypes, uncontrolled cell proliferation, defective stem cell differentiation, and splenomegaly, with single-splenocytes spatially-enriched in senescence-associated secretory profiles. Our studies reveal the evolutionary origin of paradigms co-regulating senescence and tumor suppression and offer strategies to exploit these reciprocal pathways for cancer prevention and therapy.
Patient Adapted Paternalism for Endomyocardial Biopsy Policy Changes in Heart Transplant Patients: A Mixed-Methods Study
Authors: Kim Hyoungmin , Cusi Vincenzo , McLenon Melissa , Fielding-Miller Rebecca , Cruz Rodriguez Jose Benjamin , Chak Jennifer , Urey Marcus Anthony , Kim Paul J. 
Published: January 2025

AbstractEndomyocardial biopsies (EMB) are invasive procedures performed in heart transplant (HTx) patients for surveillance of acute rejection. However, patient preferences for replacing EMBs with noninvasive assays in the context of potential institutional policy changes are unknown. A mixed-methods design was used with 28 semi-structured patient interviews and 123 self-administered online survey questionnaires in English and Spanish between January to June 2023. Additionally, we performed semi-structured interviews with 18 HTx team members. Three dominant themes were identified: alleviating patient anxiety and distress, consistent patient-provider communication, and strong interpersonal trust with the HTx team. We found that strong interpersonal trust with the HTx team by the patients was more highly prioritized than their own opinions on whether to replace EMBs with noninvasive assays. Thus, HTx patients often considered surveillance EMBs important to their care (93%), based on the recommendations provided by their HTx team. HTx faculty physicians stated that more multicenter trials are needed prior to replacing EMBs with noninvasive assays. In conclusion, patients identified strong interpersonal trust with HTx team members to justify patient adapted paternalism, where the provider decides in accordance with the patient’s situation, as their preferred shared decision-making paradigm when considering institutional policy on surveillance EMBs.
High Pathogenicity Avian Influenza Virus (HPAIV) H5N1 clade 2.3.4.4b recovered from a kelp gull (Larus dominicanus) in the South Shetland Islands, Antarctica
Authors: Ogrzewalska Maria , Pereira Elisa Cavalcante , Vanstreels Ralph Eric Thijl , Campista Emandi , Correa Junior Leonardo , Macedo Larissa , Appolinario Luciana Reis , Brandão Martha Lima , Vilela Roberto , Degrave Wim , Motta Fernando Couto , Siqueira Marilda Mendonca , Resende Paola Cristina 
Published: January 2025

AbstractWhole-genome analysis of the earliest-detected High Pathogenicity Avian Influenza Virus (HPAIV) H5N1 clade 2.3.4.4b detected in Hannah Point, Antarctica (January 2024) reveals close relatedness to strains that circulated in pinnipeds and seabirds along the Atlantic coast of South America during the second half of 2023.
Antimicrobial resistance, pathogenicity and virulence patterns ofEscherichia coliisolated from cockroaches (Blattella germanica) across diverse environments: a public health concern
Authors: Sigma Sanzila Hossain , Ashraf Md. Nahid , Karmakar Susmita , Rimi Sabrina Sultana , Chakraborty Sourav , Siddique Mahbubul Pratik , Hassan Jayedul , Islam Md. Alimul , Rahman Md. Tanvir , Islam Md. Safiqul , Hossain Muhammad Tofazzal 
Published: January 2025

AbstractThis investigation explores the prevalence and antimicrobial resistance (AMR) ofEscherichia coliisolated fromBlattella germanica(cockroaches) from diverse locations, including homes, kitchens, and laboratories, over the course of six months, from August 2022 to January 2023. A total of 125 cockroaches were analyzed, yielding 67 (53%) of positiveE. coliisolates, with kitchen environments having the highest incidence (57.77%). The existence of virulence genes (stx1,stx2, andrfbO157) was confirmed by pathogenicity assessments carried out on mouse model, which led to a considerable increase in morbidity and mortality. 82.08% of isolates showed evidence of resistance to at least one antibiotic, according to the antimicrobial susceptibility test with β-lactams displaying the highest rates of resistance. Remarkably, complex resistance patterns were observed in 77.61% of the isolates, which were categorized as multidrug-resistant. Multiple antibiotic resistance genes (ARGs) were found by molecular analysis, particularlyblaTEMandtetAas well as virulence-associated genes (VAGs) linked to extraintestinal pathogenicE. coli. Phylogenetic grouping indicated that 90.38% of the MDR isolates belonged to virulent groups B2 and D. These findings highlight the role of cockroaches as potential reservoirs for pathogenicE. coli, raising significant public health concerns regarding AMR. The study underscores the imperative need for thorough investigation and feasible control strategies to ease the dissemination of AMR in diverse contexts.
Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection
Authors: Agrawal Ragini , Pal Virender Kumar , Suhas KS , Menon Gopika Jayan , Singh Inder Raj , Malhotra Nitish , Naren CS , Ganesh Kailash , Rajmani Raju S , Narain Seshasayee Aswin Sai , Chandra Nagasuma , Joshi Manjunath B , Singh Amit 
Published: January 2025

AbstractViruses exploit host metabolism for replication and immune-regulation. Understanding how SARS-CoV-2 alters the host metabolism may lead to treatments for COVID-19. We report that a ubiquitous gaseous molecule, hydrogen sulfide (H2S), regulates redox, metabolism, and mitochondrial bioenergetics to control SARS-CoV-2. Virus replication is associated with down-regulation of the H2S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase(3-MST), resulting in diminished endogenous H2S levels. Inhibition of CTH resulted in SARS-CoV-2 proliferation. A slow-releasing H2S donor, GYY4137, diminished virus replication by inducing Nrf2/Keap1 pathway, restoring redox balance and mitochondrial bioenergetics. Treatment of SARS-CoV-2-infected animals with GYY4137 suppressed viral replication, ameliorated respiratory pathology, and restored antioxidant gene expression. Notably, whole-body plethysmography showed improved pulmonary function variables, including pulmonary obstruction and end-expiratory pause upon GYY4137 treatmentin vivo. Data extend our understanding of H2S-mediated regulation of viral-infections, and open new avenues for investigating the pathogenic mechanisms and therapeutic opportunities for coronavirus-associated disorders.
Intrahepatic crystals from elevated dietary cholesterol are sufficient to stiffen the liver
Authors: Li David , Loneker Abigail E. , Safraou Yasmine , Ford Jamie , Mihelc Elaine , Levental Kandice R. , Levental Ilya , Sack Ingolf , Janmey Paul A. , Wells Rebecca G. 
Published: January 2025

AbstractChronic lipid accumulation is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), and dyslipidemia is associated with disease progression and poorer patient outcomes. Tissue stiffening is an established fibrogenic cue, but how changes in lipid accumulation affect tissue mechanics is not fully understood. Here we show that cholesterol-containing lipid crystals stiffen steatotic liver tissue. We show that rats fed elevated dietary cholesterol develop both liquid and solid cholesterol-containing lipid crystals in the liver. While steatotic livers without crystals are softer than control livers, livers with lipid crystals show increased baseline stiffness and compression stiffening as well as increased progression to fibrosis. Lipid extracts from livers containing crystals stiffen fibrous tissue mimics, while depletion of cholesterol using methyl-ꞵ-cyclodextrin reduces both crystal abundance and tissue stiffness. Our results demonstrate in a rat model that a high cholesterol diet leads to formation of liquid and solid crystals and that cholesterol-containing crystals stiffen tissues. This work implicates lipid crystals arising from dyslipidemia as a key driver of MASLD progression. The presence of cholesterol crystals could lead to new diagnostic tools for progressive MASLD and could be a therapeutic target.
Plasma Proteomic Profiles Predict the Risk of Coronary Artery Disease in the UK Biobank Cohort
Authors: Zhang Chenhao , Ji Xiangwen , Cui Chunmei , Bai Xueke , He Guangda , Chen Liang , Cui Qinghua 
Published: January 2025

AbstractCoronary artery disease (CAD) is a complex, multifactorial, and serious condition influenced by genetic, environmental, and lifestyle factors. Thus, it is crucial to develop strategies to predict the risk of CAD for individuals. Plasma proteomics provides a powerful framework for identifying novel biomarkers, discovering potential therapeutic targets, and further improving risk stratification. Here, we examined the association between 2,919 plasma proteins and incident CAD in the UK Biobank cohort (n=35,778). As a result, we identified 576 proteins significantly associated with CAD and found significant alterations in key biological pathways, including signal transduction, immune regulation, and chemotaxis, before CAD onset. Subsequently, we developed machine learning models to predict CAD onset at different time intervals (5 years, 10 years, over 10 years, and entire cohort), demonstrating superior performance over models based on polygenic risk scores (ΔAUC = 0.052), and Pooled Cohort Equations (ΔAUC = 0.049). Notably, the integration of PRS with proteomic data resulted in a marked enhancement in predictive accuracy (AUC = 0.779), comparable to the full model (AUC = 0.780). Key plasma protein predictors, including MMP12, GDF15, and EDA2R, showed sustained importance across models predicting CAD onset at multiple time points. Additionally, Mendelian randomization analysis provided robust evidence for a causal relationship between six plasma proteins and CAD, including MMP12, LPA and PLA2G7, highlighting their potential as therapeutic targets. In conclusion, our study elucidates the plasma proteome associated with CAD, reveals underlying pathogenic mechanisms, and provides valuable insights for identifying high-risk individuals and advancing precision medicine.