Association of urate-lowering therapies with abdominal aortic aneurysm growth and clinical events in men: A population-based cohort study

Abstract: Abdominal aortic aneurysms (AAA) are potentially life-threatening if they rupture. Xanthine oxidase inhibitors have been suggested to reduce aneurysm growth via urate-lowering and antioxidative mechanisms, though their clinical efficacy remains uncertain. The primary objective of this prospective cohort study was to estimate potential associations between urate-lowering therapies and AAA growth, and secondarily risk of rupture, surgery, all-cause mortality, and major adverse cardiovascular events (MACE), in men aged 65-74. This population-based cohort study included data from two large cardiovascular screening trials. The two Danish AAA male cohorts contributed with baseline characteristics, including AAA measurements through ultrasound and computed tomography scans. Participants were followed for five years through linkage with the Danish national health registries. Prescription records defined the exposure of urate-lowering therapies, and participants were categorised as users or non-users. Growth rate was examined using multivariate linear regression, and the secondary outcomes were evaluated using Cox regression. This study included 998 men, of whom 73 (7.3%) were exposed to urate-lowering therapies, with a mean defined daily dose of 0.377 per day. During 3 993 person-years, an insignificant mean difference of 0.28 mm/year (95%CI: -0.96-1.52, p = .66) in AAA growth was observed between users and non-users. No associations between urate-lowering therapies and risk of surgery, rupture, all-cause mortality, or MACE were observed. The use of urate-lowering therapies was not associated with a reduction in AAA progression. These findings do not support a clinically meaningful effect of urate-lowering therapies on aneurysm progression in men with AAA.

Bøhling Dybdahl K
Bernal M
Dahl M
DANCAVAS trialists
Obel LM
Lindholt JS
Skovbo JS

Humans
Male
Aortic Aneurysm, Abdominal
Aged
Uric Acid
Cohort Studies
Prospective Studies
Denmark
Disease Progression
Gout Suppressants


Concordant RNA-protein evidence and human tissue metabolomics prioritize UPP1-associated nucleotide remodeling in prostate cancer

Abstract: Prostate cancer (PCa) is characterized by molecular heterogeneity and metabolic reprogramming, but the relationships among transcriptomic, proteomic, and metabolic signals remain incompletely defined. Here, we present a human-centered, cross-dataset analysis of public RNA, protein, and metabolomics data in PCa. We analyzed RNA and protein profiles from PC3 parental and drug-resistant cells together with an independent human matched tissue metabolomics dataset from Metabolomics Workbench (ST000784). RNA-protein overlap analysis identified seven genes that were significant at both layers, including five concordantly upregulated genes: UPP1, IGF2R, FLNC, DSP, and PLEC. Among these, UPP1 provided the most direct metabolic interpretation because it encodes uridine phosphorylase 1, an enzyme linked to pyrimidine salvage. Independent ST000784 matched prostate tissue metabolomics supported broader nucleotide metabolism remodeling, including significant changes in N-carbamoyl-L-aspartate, guanosine monophosphate, and adenosine 3,5-cyclic monophosphate. In contrast, uracil was not significantly altered and uridine 5'-monophosphate showed only a trend after multiple-testing correction. Repeated stratified cross-validation showed that UPP1-containing candidate gene sets achieved high within-layer AUC values in RNA and protein data, while nested statistical benchmark models also performed strongly. These results prioritize a UPP1-associated nucleotide remodeling hypothesis in PCa, but do not establish causal regulation of metabolite abundance or clinical diagnostic utility. Future matched multi-omics and perturbation experiments are required.

Chen X
Su W
Zhou Q
Qi Y
Xie J
Tang Y
Tang X
Fu H

Humans
Male
Prostatic Neoplasms
Metabolomics
Uridine Phosphorylase
Gene Expression Regulation, Neoplastic
Metabolic Reprogramming
Nucleotides
PC-3 Cells


It would be really great if I had greater confidence and ability there: Understanding the primary care physician experience with nutrition in training, clinical practice, and interprofessional collaboration

Abstract: Primary care physicians (PCPs) are on the front lines of health promotion and disease prevention, yet evidence supports a longstanding gap in physicians' capacity to counsel about diet, a key factor in patient health and chronic disease risk. Momentum to address the nutrition training needs of physicians is growing; however, challenges PCPs experience due to inadequate training are further complicated by clinical practice barriers. This study seeks to better understand the complex problem PCPs face addressing nutrition with patients to inform potential solutions. This qualitative study takes a design thinking approach to understanding the problem by learning from PCPs about their experience, challenges, and priorities addressing nutrition with patients. Findings from semi-structured interviews with 32 PCPs revealed that while they value nutrition and believe they have an important role in addressing diet with patients, their role as a generalist in addressing nutrition lacks clarity. PCPs describe learning their current approach to nutrition primarily outside of formal medical training, resulting in variability and inconsistency in approaches and recommendations and general frustrations about their ability to give actionable guidance. While registered dietitians (RDs) are often viewed as valuable support for patients, PCPs describe multiple challenges to RD utilization and subsequently at times may be the only ones with the opportunity to address diet with patients. Additional system- and societal-level barriers, such as time limitations and the food environment, further complicate PCPs' experiences advising patients about nutrition. Main limitations of this study are limited generalizability from recruiting graduates of a single medical school and PCPs with greater interest in nutrition or more frustration with their current approach to nutrition may have been more likely to participate. Our results support the need to clearly define a realistic role for PCPs as generalists addressing nutrition. Clarified expectations in turn can inform nutrition training of physicians and guiding frameworks and strategies for giving practical, evidence-based nutrition guidance. PCPs also need increased support through access to resources, strategies to improve RD collaboration, and attention to system- and societal-level challenges influencing dietary interventions in primary care.

Hildebrand CA
Agrawal S
Albin J
Beck Dallaghan GL
Chen E
Gaviria D
Gilliland KO
Hilton A
Keyserling TC
Mayer-Davis E
Ammerman AS

Humans
Physicians, Primary Care
Interprofessional Relations
Female
Male
Cooperative Behavior
Adult


Deep learning architectures for EEG-based classification of Dravet syndrome: A comparative study of pre-trained and non-pretrained hybrid CNN-LSTM models

Abstract: This study explores the potential of artificial intelligence (AI) using a hybrid deep learning Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) framework, for EEG-based classification and analysis of Dravet Syndrome (DS). The study cohort comprised nine pediatric patients with DS, confirmed through either a heterozygous pathogenic mutation in the SCN1A gene or a clinical diagnosis consistent with established diagnostic criteria. In addition, EEG recordings from age-matched healthy control subjects and pediatric patients with non-Dravet epilepsy ("abnormal" EEG) were included. Data on demographic information, seizure characteristics, developmental skills, cognitive functions, and genetic results were gathered from patient records. EEG recordings were analyzed using a subject-independent leave-one-subject-out validation strategy, spatial and temporal features by employing this model on preprocessed EEG data, effectively differentiating DS patients from Abnormal cases and healthy controls. Among the evaluated CNN-LSTM models, the pre-trained architecture achieved superior performance with improved stability across most subjects, with an overall accuracy of 85%, balanced accuracy of 85%, a macro-averaged F1-score of 0.85, and a macro-averaged ROC-AUC of 0.87, demonstrating stable performance for multi-class EEG classification of DS, Abnormal, and control subjects. The non-pretrained model showed reduced sensitivity and increased inter-class confusion, particularly for DS and Abnormal classes. This study demonstrates that a pre-trained CNN-LSTM framework can support automated EEG-based classification of DS-related patterns as a proof-of-concept methodological approach, even in the context of limited subject availability. EEG-specific pretraining improves classification consistency and feature separability compared with training from scratch, highlighting the value of representation learning for rare epilepsy syndromes. Larger multi-center datasets and prospective validation will be required to assess robustness, generalizability, and clinical utility.

Hussain S
Jawed S
Mir A
Ibrahim Ali M
Al-Baradie R
Alaqili N
Nassim Ali EM
Bashir S

Humans
Epilepsies, Myoclonic
Electroencephalography
Deep Learning
Convolutional Neural Networks
Child
Long Short Term Memory
Female
Male
Child, Preschool
NAV1.1 Voltage-Gated Sodium Channel
Case-Control Studies


Schisandrins as novel efflux pumps inhibitors and non-antibiotic compounds against multi- and extensively-drug resistant clinical strains of Salmonella typhi: An in-vitro study

Abstract: Typhoid is a significant global health challenge due to its high pathogenicity and antimicrobial resistance. Salmonella typhi (S.typhi) can switch its lifestyles between biofilm and planktonic phase which allows it to evade host defenses and develop resistance to antibiotics. Salmonella sp. harbors multiple genes encoding efflux-pumps systems whose up-regulation contributes to multi-drug resistance (MDR) and extensive drug-resistance (XDR). To overcome the battle against resistant S. typhi strains, novel non-antibiotics inhibitors are required for inhibitory application. This study assesses the inhibitory effect of lignans against drug resistance of S. typhi. Clinical resistant and sensitive strains of S. typhi were obtained and characterized. The inhibitory effect of lignans, specifically Schisandrin A and B, purified from the plant Schisandra chinensis, are found to be effective non-antibiotic inhibitors were evaluated through standard microbiological techniques like growth curve and time-kill assays. Impact on bacterial morphology was analyzed using scanning electron microscopy (SEM). Our study explores two approaches, such as efflux pumps (EPs) inhibition and antibiofilm assays. Using colony-forming unit (CFU) assays, growth curve analysis, and SEM imaging, we observed significant bacteriostatic effects, with Schisandrin B causing notable membrane disruption. Schisandrin B also showed remarkable biofilm inhibition (90.33%) and strong efflux pumps inhibition. This study offers a strong basis for future research on addressing antibiotic resistance in clinically relevant pathogens.

Shafique I
Rana NF
Ahmad N
Tanweer T
Javaid S
Albaldi FO
Elbehairi SEI
Shati AA
Sheikh HM
Menaa F

Lignans
Salmonella typhi
Polycyclic Compounds
Cyclooctanes
Drug Resistance, Multiple, Bacterial
Microbial Sensitivity Tests
Anti-Bacterial Agents
Biofilms
Humans


Integrative multi-omics and machine learning identify CHRNA1 putative circadian-immune hub in COPD

Abstract: Circadian rhythm disruption is increasingly recognized as a contributor to chronic inflammatory disorders; however, its specific significance and underlying mechanisms in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to identify circadian rhythm-associated biomarkers in COPD and explore their diagnostic value, immune correlations, and therapeutic potential. This study integrated four lung transcriptomic datasets from the public GEO database (GSE151052, GSE38974, and GSE76925 as the discovery set, and GSE47460 as the validation set). Differentially expressed circadian rhythm‑related genes (DECRRGs) were identified by intersecting differentially expressed genes with circadian rhythm‑related genes. Functional enrichment analyses (GO and KEGG) were performed, and three machine learning algorithms were applied to screen for signature DECRRGs. An exploratory risk stratification model based on multivariate logistic regression was constructed and evaluated. Immune cell infiltration was assessed using CIBERSORT, and single-cell RNA sequencing analysis was conducted to localize the distribution of key circadian rhythm genes within specific lung cell populations. Finally, the expression of a core gene CHRNA1 was validated by qRT-PCR in peripheral blood samples from COPD patients and healthy controls. We identified eight circadian rhythm-associated feature genes, among which CHRNA1 emerged as a consistently upregulated hub gene in COPD. An exploratory risk stratification model based on these genes exhibited good discriminatory ability in the discovery cohort (AUC = 0.856, 95% CI: 0.806-0.902). Differential expression of CHRNA1 was validated in an independent cohort and correlated significantly with pro-inflammatory immune infiltration, including increased M1 macrophages and CD8 ⁺ T cells. Single-cell transcriptomics further localized CHRNA1 expression predominantly within B cells in COPD lung tissue. In silico drug screening and ceRNA network analysis predicted potential therapeutics (e.g., amitriptyline, rocuronium bromide) and regulatory miRNAs/lncRNAs. Finally, qRT-PCR confirmed a marked upregulation of CHRNA1 in peripheral blood from COPD patients (*p* < 0.0001). Our findings suggest that CHRNA1 may serve as a candidate circadian rhythm‑associated immunomodulator in COPD. It demonstrates consistent upregulation across cohorts and shows a significant association with pro‑inflammatory immune infiltration. Single-cell analysis revealed that CHRNA1 is predominantly expressed in pulmonary B cells. The exploratory risk stratification model and predicted therapeutic candidates highlight the translational potential of targeting circadian disruption in COPD, though prospective validation is needed before clinical application.

Zhang L
Li Z
Xia T
Yang T
Fu J
Lu Y
Xu J
Han K

Pulmonary Disease, Chronic Obstructive
Humans
Machine Learning
Circadian Rhythm
Receptors, Nicotinic
Multiomics
Gene Expression Profiling
Male
Transcriptome
Lung
Biomarkers
Female


Integrative network pharmacology, transcriptomics, and molecular docking identify candidate Centella asiatica constituents and targets in neurodegenerative diseases

Abstract: Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), are progressive disorders with limited therapeutic options. Centella asiatica (C. asiatica), a medicinal and edible plant, has been reported to exert neuroprotective and anti-neuroinflammatory properties. Yet, the mechanisms underlying its effects against neurodegenerative diseases remain largely unclear. We employed an integrative strategy combining network pharmacology, transcriptomic analyses, machine learning and molecular docking to prioritize disease-associated molecular networks and candidate compound-target relationships in AD, PD and HD. Sixteen candidate constituents of C. asiatica met the predefined drug-likeness, gastrointestinal absorption and blood-brain barrier permeability criteria, yielding 370 unique predicted targets. Disease-gene mining identified 983 AD-associated genes, 1,103 PD-associated genes, and 3,316 HD-associated genes. Integration of compound targets, disease-associated genes, and transcriptomic profiles prioritized five hub genes in PD (CCKAR, MAPK8, PSEN2, SLC6A3, and TH), four in AD (APP, PGK1, PIK3CA, and TTR), and four in HD (CHRND, HSP90AA1, PRKCQ, and TH). Enrichment analyses highlighted disease-relevant processes involving neurotransmitter signalling, cAMP and calcium pathways, MAPK-related responses and inflammatory regulation. ROC analyses provided additional support for the discriminatory performance of the prioritized genes in independent datasets, whereas molecular docking identified favourable predicted Vina docking scores and structurally plausible interactions between selected compounds and hub targets. This integrative computational analysis prioritizes candidate C. asiatica constituents, putative disease-associated targets, and molecular pathways in AD, PD, and HD. The findings provide a foundation for subsequent biochemical, cellular, and in vivo validation.

Xie Y
Lim CT
Lam XJ
Cheah PS
Ling KH
Huang T

Molecular Docking Simulation
Neurodegenerative Diseases
Centella
Humans
Network Pharmacology
Triterpenes
Transcriptome
Gene Expression Profiling


Real-world regorafenib use among patients with advanced gastrointestinal stromal tumor in the United States

Abstract: Gastrointestinal stromal tumors (GIST) are the most common gastrointestinal soft tissue sarcoma. Tyrosine kinase inhibitors are guideline-recommended therapy; however, resistance often occurs, requiring subsequent therapy. Regorafenib is a multikinase inhibitor approved for third-line therapy. Real-world data surrounding regorafenib's use and place in therapy are limited. To understand real-world regorafenib utilization and patient characteristics among US patients with advanced GIST. This retrospective cohort claims analysis used data from Merative™ MarketScan® research databases and included patients with ≥1 pharmacy claim for regorafenib during the identification period (10/2015-5/2023) and ≥1 GIST diagnoses any time prior to/on index date (first regorafenib prescription claim). Primary outcomes included duration of therapy (DOT) and time to next therapy (TTNT). Outcomes were stratified based on prior GIST treatment during the baseline period (BL) and initial regorafenib dose (i.e., low dose [LD] or regorafenib standard dose [RSD]) as of the index date. Nearly half (45.2%) of patients received imatinib and sunitinib prior to regorafenib initiation, and 73.5% received RSD. Patients who received prior imatinib or sunitinib alone before regorafenib had a numerically longer median DOT with regorafenib than those who received both in the BL before regorafenib (142.5 days [IQR: 87-257.5] vs 95 days [IQR: 53-192]). Patients receiving LD and RSD demonstrated similar median DOT (103.0 days [IQR: 41.5, 210.5] vs 94.5 days [IQR: (35.0, 171.0]) and TTNT (143 days [IQR: 70-293] vs 141 days [IQR: 77-191]). Patients on LD and RSD had similar DOT and TTNT. Acknowledging the limitations from this real-world data, patients with prior imatinib or sunitinib alone appeared to have longer DOT on regorafenib than those who received both. Further research is warranted to explore the clinical benefits of these differences.

Denu RA
Appukkuttan S
Hocum B
Liao N
Katta A
Heo J
Schroader B
Singh R
Babajanyan S
Somaiah N

Humans
Phenylurea Compounds
Gastrointestinal Stromal Tumors
Pyridines
Female
United States
Retrospective Studies
Male
Middle Aged
Aged
Gastrointestinal Neoplasms
Antineoplastic Agents
Protein Kinase Inhibitors
Adult


Sustainable conversion of waste plastics to biofuel: Process insights and fuel characteristics

Abstract: Plastic consumption has become pervasive in modern society, with over 300 million metric tonnes produced annually worldwide, contributing significantly to municipal waste. In Bangladesh, where annual per capita plastic use has risen to 22 kg as of 2022, innovative solutions for managing plastic waste are urgently needed. This research introduces a novel approach to the pyrolysis of various plastics (PET, PVC, PP, HDPE) within a temperature range of 300 °C to 550 °C to produce pyrolytic bio-oil and biochar. We established optimal conditions for each plastic type-500 °C for PET, PVC, and HDPE, and 450 °C for PP-resulting in maximized yields of high-quality liquid oils (61.3% for PP and 47.23% for HDPE). Unique to this study, we innovatively adjust the pyrolysis process parameters to enhance the yield and quality of the derived bio-oils, tailored specifically to the types of plastics treated. The liquid products were characterized as predominantly consisting of C6-C16 hydrocarbons, aligning them closely with naphtha, gasoline, and diesel specifications, suitable for use as renewable fuels. Furthermore, our research applies FTIR and GC-MS analyses in a novel way to provide a detailed examination of these bio-oils, revealing significant quantities of paraffinic hydrocarbons in PP and olefins and naphthenes in HDPE, contributing to their potential fuel applications. The solid char byproducts were also comprehensively characterized using SEM and XRD, providing insights into their suitability for various industrial applications. This study not only demonstrates the potential of pyrolysis to transform waste plastics into valuable renewable energy resources but also advances the technological framework for sustainable waste management practices, marking a significant leap forward in the efficiency and application of plastic waste conversion technologies.

Banik U
Huda MN
Harun-Ur-Rashid M
Ahmmed R
Hosen MA
Ismail M

Plastics
Biofuels
Pyrolysis
Waste Products
Charcoal
Plant Oils
Polyphenols


From theory to practice: A case study on estimating the costs of improving animal welfare on Simmental alpine dairy farms

Abstract: This case study estimates the economic implications of enhancing animal welfare (AW) in Alpine dairy farming, specifically focusing on Simmental cattle in both conventional (CON) and organic (ORG) farms. Given the increasing demand for higher welfare standards from consumers and policymakers, it is important to assess the economic feasibility of implementing these practices. The primary aim of this study is to develop a proof of concept for estimating the costs involved in meeting specific AW standards. Data were collected from 30 dairy farms (15 CON and 15 ORG), and AW scores were evaluated using both resource-based and animal-based indicators (total score of 90 points). Additionally, AW costs were assessed by calculating the cumulative additional costs, offset by potential benefits. Results show ORG farms achieve higher AW scores (73.99) compared to CON farms (70.28) but incur significantly higher production costs (€1.263/kg ECM for ORG vs. €0.977/kg ECM for CON), primarily due to the dilution effect caused by lower milk production on ORG farms. A nonlinear relationship between AW scores and AW costs was also observed, indicating that higher AW scores in initial farm conditions could, in some cases, lead to cost savings, particularly in larger and more efficient farms. The study emphasizes the need for clearly defined AW standards and a corresponding scoring system that reflects both the welfare impacts on animals and the economic feasibility for farmers. Further, we argue that the aggregation of AW scores should not merely categorize welfare on a simple best-to-worst continuum. Rather, it should account for the specific targets and conditions that policymakers and consumers are willing to support financially.

Triatmojo A
von Davier Z
Fichter G
Gauly M
Zanon T

Animals
Cattle
Animal Welfare
Dairying
Female
Farms
Milk


DiSCoKit: An open-source toolkit for deploying live LLM experiences in survey research

Abstract: In scientific studies of human-AI interaction dynamics, researchers often need to present participants with opportunities to interact with live large-language models (LLMs). However, technical and practical challenges (from survey platform limitations and logging chat data to manipulating AI behaviors for experimental designs) often inhibit survey-based deployment of AI stimuli. We developed DiSCoKit-an open-source toolkit for deploying live LLM experiences (e.g., ones based on models delivered through Microsoft Azure portal) through JavaScript-enabled survey platforms (e.g., Qualtrics). We describe the toolkit's scientific motivation, architecture, and operation. We also offer an example of toolkit deployment and customization, along with discussing its possibilities and limitations. Altogether, DiSCoKit gives researchers a flexible, secure, scalable solution for deploying naturalistic LLM stimulus experiences through online surveys.

Banks J
Stromer-Galley J
Singh S
Capano C

Large Language Models
Humans
Surveys and Questionnaires
Software
Artificial Intelligence


A cross-domain deep learning framework for remaining useful life prediction in industrial applications

Abstract: Accurate prediction of Remaining Useful Life (RUL) is critical for predictive maintenance and minimizing downtime in industrial systems. This paper presents a cross-domain deep learning framework based on a hybrid Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) architecture. Unlike domain-specific models that require handcrafted features, the proposed framework extracts local degradation features through CNN layers and captures long-term dependencies via BiLSTM networks. The model is evaluated on three heterogeneous datasets: construction machinery, continuous casting machines, and lithium-ion batteries. Experimental results show that CNN-BiLSTM consistently outperforms baselines, achieving up to 22% lower RMSE compared to GRU and 30-50% lower RMSE compared to traditional models. On the construction dataset, it achieves an MAE of 48.2 hours and RMSE of 67.1 hours (R2 = 0.88), outperforming GRU by 20%. For the casting dataset, the model attains an MAE of 87.6 tons and RMSE of 113.9 tons (R2 = 0.87), surpassing Random Forest by over 35%. On the battery dataset, CNN-BiLSTM reduces the MAE to 49.6 cycles and RMSE to 72.8 cycles (R2 = 0.89), while also achieving the lowest Timeliness Score (27.5) and PHM08 Score (192.4). Cross-domain experiments are evaluated under two settings: zero-shot transfer, where the model is trained on one source domain and directly tested on a different target domain without using labeled target-domain samples, and fine-tuned transfer, where 20% of labeled target-domain samples are used to update only the fully connected layers while keeping the CNN and BiLSTM layers frozen. The zero-shot results reflect the effect of domain shift, while the fine-tuned results show that lightweight transfer adaptation reduces RMSE by 25-40% across domains. These findings indicate cross-domain adaptability under limited target-domain supervision rather than fully unsupervised cross-domain generalization. These results highlight the feasibility of a unified CNN-BiLSTM framework for scalable, cross-domain RUL estimation and its suitability for real-world prognostic applications.

Saha S
Pervaiz MA
Rahman MS
Hasan R
Rahman A

Deep Learning
Long Short Term Memory
Convolutional Neural Networks
Industry
Prediction Algorithms
Predictive Learning Models
Neural Networks, Computer


The prognostic significance of stress hyperglycemic ratio in critically Ill patients with hypertension: A study using the MIMIC-IV database

Abstract: Traditional ABG is susceptible to interference from acute stress and daily fluctuations, making it difficult to accurately assess true acute blood glucose surges. To bridge this gap, we adopted the Stress Hyperglycemia Ratio (SHR), which reflects true acute hyperglycemia by controlling for baseline glucose status. SHR is associated with critical illness and has been shown to associated with in-hospital mortality. However, there is a lack of studies investigating SHR and its prognostic significance in patients with hypertension. This study utilized the Medical Information Mart for Intensive Care IV database (MIMIC-IV) to extract patient information. All subjects were divided into four groups based on the quartiles of SHR. Kaplan-Meier (KM) curves were utilized to assess the relationship between SHR and all-cause mortality at 30, 90, 180, and 365 days. The relationship between the SHR index and prognosis was evaluated using restricted cubic spline (RCS) regression and Cox proportional hazards regression. At the same time, subgroup analyses were performed for gender, age, diabetes, myocardial infarction, congestive heart failure, cerebrovascular disease, and paraplegia. A total of 2,140 participants with essential hypertension were included in the study. The KM curve analysis revealed that elevated levels of the SHR index were significantly associated with an increased risk of all-cause mortality at 30, 90, 180, and 365 days (log-rank P < 0.05). Moreover, multivariate analysis revealed that the SHR index remained significantly associated with mortality risk (P < 0.001). RCS analysis revealed a nonlinear, inverse U-shaped association between SHR and all-cause mortality (P < 0.05). Subgroup analysis showed statistically significant differences in all-cause mortality across gender, age, diabetes, myocardial infarction, heart failure, cerebrovascular disease, and paraplegia. In critically ill patients with hypertension, a high level of SHR index is associated with all-cause mortality. The SHR index may be a potential prognostic indicator for assessing illness severity in ICU patients with hypertension.

Li Z
Wu Y
Jin Q
Lou T
Kang Y
Wang X
Sun N
Ni T
Zhu Z
Wang M
Li Q

Humans
Female
Prognosis
Critical Illness
Hyperglycemia
Hypertension
Male
Middle Aged
Aged
Databases, Factual
Blood Glucose
Kaplan-Meier Estimate
Proportional Hazards Models
Hospital Mortality


Surveillance of Escherichia coli clones and their antimicrobial resistance profiles in wastewater and drinking water treatment plants of Barcelona, Spain

Abstract: Antimicrobial resistance (AMR) is a major global health threat, and environmental reservoirs such as wastewater (WWTPs) and drinking water treatment plants (DWTPs) may facilitate its persistence and spread despite reducing bacterial loads. We investigated 152 antibiotic-resistant Escherichia coli strains collected across treatment stages from two WWTPs and one DWTP in Barcelona, Spain. Strains were characterized through antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, biofilm assays, and screening of antimicrobial resistance genes (ARGs), virulence factors (VFGs), biocide and heavy-metal tolerance genes (HMTGs). Although E. coli bacterial loads decreased along treatment, AMR remained highly prevalent: 85.5% of strains were multidrug-resistant (MDR), 5.3% extensively drug-resistant, and 11.2% carbapenemase-producers. Strains harboring integrase genes were 2.4 to 11.8 times more likely to harbor ARGs for sulfonamide, aminoglycoside, phenicol, trimethoprim, mercury and quaternary-ammonium compounds. Strains carrying blaCTX-M genes were 3.0 to 20.3 times more likely to carry VFGs, while high-risk clones were 3.2 to 7.0 times more associated with VFGs. Some MDR and high-risk E. coli clones persisted in reclaimed water, and one MDR strain was detected at the DWTP inlet. These findings highlight environmental AMR reservoirs as a public health concern and support a One Health approach integrating antibiotic stewardship and environmental monitoring.

Ballén V
Cornielle E
Pinar-Méndez A
Vilaró C
Galofré B
Martí S
González-Diaz A
Sanz S
Vilamala A
Soto SM

Escherichia coli
Spain
Wastewater
Drinking Water
Water Purification
Anti-Bacterial Agents
Microbial Sensitivity Tests
Multilocus Sequence Typing
Drug Resistance, Multiple, Bacterial
Drug Resistance, Bacterial
Water Microbiology


A computer vision-based approach for automatically extracting data from bar chart raster images to facilitate meta-analysis of biomedical literature

Abstract: Although bar charts are widely used in scientific publications, their rasterized format within Portable Document Format (PDF) files complicates automated data extraction, hindering large-scale evidence synthesis and meta-analysis. To address this, we developed and evaluated an automated pipeline for extracting quantitative data from bar charts embedded in the biomedical literature. The four-stage pipeline comprises (1) image extraction and panel segmentation, (2) optical character recognition (OCR)-based text detection, (3) image disassembly to identify chart components, and (4) data reconstruction using numeric parsing and axis-based interpolation. The system combines edge detection, morphological operations, and convolutional neural network (CNN)-based figure classification using a transfer-learned Inception v3 model. Performance was validated on randomized controlled trials in age-related macular degeneration, with manually annotated values from a semi-automated labeling tool as the reference standard, and agreement was assessed using Bland-Altman analysis. Across 28 bar charts from ten publications, the pipeline correctly recognized 92.9% (95% confidence interval [CI], 77.4-98.0) of figure types, 96.0% (95% CI, 94.2-97.3) of text blocks, and 79.1% (95% CI, 74.7-83.0) of bars. For numerical reconstruction, 81.2% (95% CI, 76.3-85.2) of bar values fell within ±5% of the reference standard, 63.0% (95% CI, 57.3-68.3) within ±2%, and 48.6% (95% CI, 43.0-54.3) within ±1%. Bland-Altman analysis showed a small negative bias of -0.18 (95% CI, -0.34 to -0.02), with 94.9% of differences within the limits of agreement. Most outliers arose from OCR digit misclassification or ambiguous bar boundaries. This proof-of-concept study demonstrates the feasibility of automated data extraction from bar charts using a hybrid approach that combines image-processing heuristics with CNN-based classification. Although currently limited to bar charts and a single clinical domain, the pipeline represents a step toward scalable, end-to-end systems for automated evidence extraction to support meta-analyses across the biomedical literature.

Cardaras A
Kim S
Yuan Y
Livnat I
Yanagihara RT
Saul R
De Oca GM
Zheng K
Browne AW

Convolutional Neural Networks
Image Processing, Computer-Assisted
Humans
Macular Degeneration
Algorithms
Publications


Microbial communities in the rhizosphere of three Mentha species: Links to soil properties and essential oil profiles

Abstract: Mentha species are widely cultivated aromatic plants valued for their essential oils and antimicrobial properties. However, despite their agricultural and pharmacological significance, limited information is available on how different Mentha species influence rhizosphere microbial communities and their relationships with soil physicochemical parameters and essential oil composition. In this study, we examined the rhizosphere microbiota of three closely related taxa - Mentha × villosa B10, M. spicata B17, and M. suaveolens J17 - cultivated under uniform field conditions. Rhizosphere and bulk soils were analyzed for physicochemical properties, microbial composition (16S rRNA, ITS sequencing), essential oils (gas chromatography-mass spectrometry), and arbuscular mycorrhizal colonization. Bacterial communities were dominated by the phyla Actinomycetota, Pseudomonadota, Acidobacteriota, Bacillota, and Chloroflexota, while fungal communities were primarily composed of Ascomycota, Mortierellomycota, Basidiomycota, and Rozellomycota. Rhizosphere soils exhibited higher fungal diversity than bulk soils, with Glomeromycota detected exclusively in rhizosphere. Microbial community composition differed significantly among Mentha taxa: M. spicata B17 displayed the lowest bacterial diversity, the most distinct microbial assemblages, and the highest arbuscular mycorrhiza colonization. Soil properties - particularly humus content, phosphorus, potassium, and sodium - were strongly correlated with bacterial diversity, while fungal communities showed weaker associations. Integration of essential oil data revealed genotype-dependent chemical profiles: Mentha × villosa B10 and M. spicata B17 were characterized by high proportions of L-carvone and limonene, whereas M. suaveolens J17 was dominated by cis-piperitone epoxide and piperitenone oxide. Together, these findings demonstrate that even closely related Mentha cultivars can harbor distinct rhizosphere microbiota, associated with both plant chemical traits and soil characteristics. This study highlights the complex interactions between aromatic plants, soil chemistry, and microbial communities, offering novel insights into plant-soil-microbe interactions in medicinal and aromatic crop systems.

Wazzani Y
Tavaszi-Sárosi S
Patonay K
Olasz F
Juhász Á
Posta K

Mentha
Oils, Volatile
Rhizosphere
Soil Microbiology
Soil
Bacteria
RNA, Ribosomal, 16S
Mycorrhizae
Fungi
Microbiota
Phylogeny


A pilot trial investigating feasibility and preliminary efficacy of a task-specific step training regimen to improve balance recovery among community-dwelling older adults

Abstract: While a growing number of studies have shown positive effects of perturbation-based balance training on balance recovery after tripping, this training has employed specialized equipment that may pose a barrier for wider adoption. To address this, the purpose of this pilot trial was to evaluate the feasibility and preliminary efficacy of a novel, low-resource (i.e., not requiring specialized equipment) version of perturbation-based balance training referred to here as task-specific step training. Thirty community-dwelling older adults (mean (SD) age: 71.8 (4.4) years) were recruited and allocated to either step training (n = 10), traditional treadmill perturbation-based balance training (n = 10), or a control group involving no training (n = 10). Participants were then exposed to two overground laboratory-induced trips while walking on a walkway. Results showed the step training group exhibited an initial recovery step that was 9.0% body height longer (p < 0.001) and 0.25 m/s faster (p = 0.011) than the control group.The step training group also exhibited a 4.8% body height longer recovery step, and a fall rate that was 39% lower (p = 0.037) when compared to the treadmill training group after lab-induced trips. While promising, these results should be interpreted with caution give the modest sample size and a potential bias between groups with respect to safety harness usage during laboratory-induced trips. A future trial with adequate statistical power to better evaluate efficacy and effectiveness of this step training on real-world trip and fall risk appears warranted. The study was registered on clinicaltrials.gov (NCT05734443).

Lee Y
Alexander NB
Franck CT
Castleberry J
Madigan ML

Humans
Postural Balance
Pilot Projects
Aged
Female
Male
Walking
Feasibility Studies
Accidental Falls
Exercise Therapy
Independent Living


Psychometric properties of the Thai version of the Illness-Specific Social Support Scale Short Version-8 (ISSS-8) among hematological malignancy patients in the Northeastern region of Thailand: A multicenter study

Abstract: Social support, which is an essential aspect influencing health, has resulted in the development of several approaches for assessment in cancer patients. The Illness-Specific Social Support Scale Short Version-8 (ISSS-8) effectively evaluates social support among diverse patient demographics; however, its psychometric validity has yet to be established in Asian cultural contexts. The objectives of this study were to translate and culturally adapt the ISSS-8 for the Thai setting and to assess its psychometric properties in patients with hematological malignancies (HMs). This study employed a convenience sampling method to select patients with HMs undergoing hospitalization at three tertiary institutions in Northeastern Thailand. Psychometric testing was conducted following the translation and cross-cultural adaptation of the ISSS-8 into Thai. A total of 350 patients were recruited. Participants were randomly divided into two groups for exploratory factor analysis (EFA) (n = 200) and confirmatory factor analysis (CFA) (n = 150). The EFA of the eight items yielded a loading from a two-factor model comprising Positive Support and Detrimental Interactions, which explained 82.44% of the variance. Cronbach's alpha (0.80) and item-total correlations (rho = 0.33-0.65) demonstrated acceptable reliability of the ISSS-8, while test-retest reliability was high (ICC = 0.924--0.934). The average variance extracted (AVE) demonstrated convergent validity for all ISSS-8 subscales, with AVEs ranging from 0.76 to 0.80. Moreover, the total ISSS-8 scale demonstrated a statistically significant but weak positive correlation with the Stanford Inventory of Cancer Patient Adjustment (r = 0.244, p < 0.001), while the Detrimental Interactions subscale was significantly and weak negatively correlated with it (r = 0.237, p < 0.001). These findings suggest that the ISSS-8 captures distinct psychosocial and illness-specific relational constructs that differ from coping self-efficacy and psychological adjustment measured by the SICPA. The ISSS-8 is a short, accurate, and valid instrument for measuring social support in Thai patients with HMs. As a result, healthcare professionals can use the ISSS-8 to assess social support in both research and clinical settings. The findings emphasize the necessity of integrating social support evaluation into cancer management and family-centered care, thereby supporting comprehensive and adaptive healthcare delivery in Thailand.

Summart U
Sangruangake M
Wamaloon C
Moungmultri A
A'la MZ

Humans
Thailand
Female
Psychometrics
Social Support
Male
Middle Aged
Hematologic Neoplasms
Adult
Surveys and Questionnaires
Aged
Reproducibility of Results
Factor Analysis, Statistical


Mapping the prevalence of household-scale livestock ownership by animal taxon in low- and middle-income countries: A prediction model using template model builder

Abstract: Animal husbandry is widely practiced on the household scale in communities in low- and middle-income countries (LMICs) and, while having economic and health benefits, exposes household members to risk of zoonotic infections to an extent that is unclear. While demand for georeferenced information on infectious disease risk factors and drivers is growing, spatial variation in livestock ownership remains poorly characterized at high resolution. This study aimed to use geostatistical methods to model and map the prevalence of livestock husbandry in LMICs for three major animal taxa: poultry, swine, and ruminants. Microdata relating to ownership of livestock animal species were sourced from various population-based survey programs which together cover the majority of LMICs and categorized. These were georeferenced and spatially matched with a panel of time-fixed environmental and demographic spatial covariates, INLA models were fitted to the resulting database, and probabilities for ownership of each livestock taxon predicted based on the model parameter estimates. The results indicated widespread poultry ownership across rural Central America, the Amazon basin, tropical Africa and river basins and forests of East Asia. Swine husbandry is the least widely practiced among the three livestock taxa and concentrated in an undulating belt of higher prevalence extending from central China, through southeast Asia to Northeastern India, though such predictions in data-sparse regions (particularly Muslim-majority areas) represent regional covariate patterns rather than fine-scale measurements. To address non-stationarity in swine spatial structure, region-specific spatial kernels were implemented. Rearing of ruminant livestock appears widespread across subequatorial Africa, Central Asia, the Gobi Desert, the Himalayas, Mongolia and northern India. The models perform impressively by most standard evaluation metrics, and the patterns in their predictions align with external evidence. The distribution of this important risk factor for infectious disease transmission can be modeled using publicly available data sources to generate plausible and potentially actionable predictions over wide geographic areas and identify regions of high exposure to animal disease reservoirs. The resulting predicted prevalence estimates are made available as supplementary files in GIS-compatible format.

Colston JM
Fang B
Ahmedjonova V
Hossain N
Kansara P
Schiaffino F
Nong MK
Revathi AA
Zaitchik B
Chernyavskiy P
Lakshmi V
Kosek MN

Animals
Livestock
Animal Husbandry
Prevalence
Developing Countries
Ownership
Family Characteristics
Humans
Swine
Zoonoses


Integrated transcriptomic analysis of LMB2-induced podocyte injury identifies conserved inflammatory and adaptive stress responses

Abstract: Podocyte injury is a central driver of progressive glomerular diseases, yet the temporal organization of podocyte-intrinsic responses remains incompletely defined. In this study, we performed an integrated re-analysis of two publicly available mouse transcriptomic datasets (GSE108629 and GSE151869) to identify conserved molecular responses to LMB2-induced podocyte injury across comparable post-injury time points. Differential expression analysis was conducted independently at Day 4 and Day 7 in each dataset, followed by cross-dataset integration at each time point by identifying shared differentially expressed genes (DEGs) with consistent directionality. The resulting Day 4 and Day 7 shared gene sets were subsequently combined to define a final pooled shared DEG set. Functional enrichment, network analysis, upstream regulator prediction, and gene set enrichment analysis (GSEA) were used to characterize conserved biological processes and regulatory features. We identified 1,418 and 1,401 shared DEGs at Day 4 and Day 7, respectively, with 725 genes defining the final pooled shared DEGs set. At Day 4, the transcriptional response was characterized by inflammatory signaling and adaptive stress-related pathways, including endoplasmic reticulum stress. By Day 7, this response expanded to include extracellular matrix remodeling, focal adhesion reorganization, sustained inflammatory signaling, and downregulation of autophagy-lysosome pathways, together with disruption of ER-to-Golgi trafficking. Network analysis highlighted RELA-centered regulatory modules alongside epigenetic- and kinase-associated regulators. Collectively, these findings support a conserved, cross-dataset biphasic transcriptional response to podocyte injury, characterized by an early adaptive inflammatory phase followed by a later maladaptive state involving extracellular remodeling and impaired proteostasis. This framework provides a reproducible, temporally organized injury signature and is consistent with stage-specific pathways as potential targets for future mechanistic and therapeutic studies.

Esmaeili MR
Nejati M
Roqanian S
Moghadasali R
Taleahmad S

Podocytes
Animals
Mice
Gene Expression Profiling
Inflammation
Transcriptome
Stress, Physiological
Transcription Factors
Signal Transduction
Gene Regulatory Networks
Endoplasmic Reticulum Stress


Analysis of the work, health and well-being experience of immigrant personal support workers in minority language contexts in Canada: Scoping review protocol

Abstract: The aging Canadian population has led to an increase in Canada's use of home and community care services. In this context, the healthcare system relies heavily on personal support workers who work in various healthcare settings. A significant proportion of these workers are immigrants, and many live in linguistic minorities. Despite their pivotal role, the experiences and working conditions of these personal support workers are underrepresented in the scientific literature, specifically in intersectional analyses. This scoping review aims to examine the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting. Studies addressing the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting, and those published in English or French. There will have no restrictions on publication date. This review will follow the JBI recommendations for scoping reviews and incorporate the PRISMA-ScR checklist. We will develop an adapted search strategy for five relevant databases (Medline [Ovide], Web of Science, Embase, CINAHL, and Google Scholar). Two independent reviewers will select full-text articles based on pre-established inclusion criteria and extracted relevant data. The results will be presented in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews) guidelines. This scoping review contributes to expanding knowledge about the professional, health, and social realities of immigrant PSWs in Canada's linguistic minority communities.

Philibert L
Plaisimond J
Lapierre J
Kaboré SS
Osomba AN
Mariano L
Bergeron F
Kiki GM
Ntanda GM

Humans
Canada
Emigrants and Immigrants
Scoping Reviews as Topic
Language
Minority Groups


Veterinarian-pharmacist collaboration in veterinary medicine: Roles, practices, and perceptions-A scoping review

Abstract: Pharmacists are expanding their participation in veterinary healthcare teams and assuming roles beyond traditional dispensing duties. However, the scope of these collaborative practices and the degree of mutual recognition vary substantially across regions. This scoping review aimed to organize the existing literature on collaboration between veterinarians and pharmacists, clarifying current roles, practical applications, and professional perceptions within the veterinary field. A scoping review was conducted to examine the roles, practices, and perceptions associated with veterinarian-pharmacist collaboration in veterinary medicine and related fields. Two researchers independently searched PubMed, Web of Science, the Cochrane Library, and Ichushi-Web, and additionally screened Google Scholar to identify gray literature (from database inception to August 2025, in English or Japanese). Records were independently screened at the title/abstract and full-text levels using predefined eligibility criteria, and relevant studies were identified. The search yielded 239 records, of which 16 studies published between 2007 and 2024 were included. Studies were conducted primarily in the United States (n = 7), New Zealand (n = 3), and Japan (n = 3); one study collected data from both Japan and Taiwan. Most studies employed cross-sectional survey designs. Pharmacist roles most frequently involved compounding and dispensing for animal patients (62.5%), followed by drug information (DI) and consultation (37.5%), inventory and supply management (25.0%), client education (18.8%), and safety and exposure control (12.5%). This scoping review demonstrates that veterinarian-pharmacist collaboration is described within a limited and regionally variable evidence base, with pharmacists most often contributing through compounding/dispensing and drug information support. Sustained and scalable implementation will require improved mutual understanding of professional roles, strengthened veterinary-specific education for pharmacists, and more robust empirical research to inform collaborative practice models.

Pharmacists
Veterinarians
Veterinary Medicine
Humans
Cooperative Behavior
Animals
Professional Role
Japan


Isolation and characterization of Candida metapsilosis from foci of chronic pododermatitis in captive steppe eagles in Kazakhstan

Abstract: Pododermatitis (bumblefoot) is a chronic, debilitating disease of the plantar surface of the foot that affects birds of prey kept in captivity worldwide. Although bacterial pathogens, especially Staphylococcus aureus, are most commonly considered as causative agents, the contribution of opportunistic yeasts to chronic, non-healing footpad lesions remains poorly characterized. Keratinophilic yeasts may sustain the disease process by degrading keratin in superficial tissues, impairing wound healing and, owing to their thermotolerance and minimal nutritional requirements, persisting in the environment of the bird's enclosure. In this study, three captive steppe eagles (Aquila nipalensis) from a single aviary in Kazakhstan, all presenting with chronic pododermatitis unresponsive to antibacterial treatment, were investigated by integrated mycological, biochemical and molecular approaches. The yeast isolates were recovered from the deep footpad lesions and identified to species level by sequencing of the ITS1-5.8S-ITS2 rDNA region. All these isolates were assigned to Candida metapsilosis, and phylogenetic analysis confirmed their close clustering with reference C. metapsilosis sequences. Phenotypic characterization showed that all isolates were thermotolerant (growth at 8-37 °C), expressed strong urease and keratinolytic activity (the latter confirmed in vitro by the hair perforation test), high saccharolytic activity and selective, weak proteolytic activity. Disk diffusion screening showed susceptibility to azoles (ketoconazole, clotrimazole, fluconazole) and reduced susceptibility to polyenes (nystatin, amphotericin B). To our knowledge, this is the first report of C. metapsilosis isolated from chronic pododermatitis lesions in captive steppe eagles. Combined with the documented in vitro virulence-associated traits and the resolution of the lesions following targeted antifungal therapy, our findings support a contributory etiological role of C. metapsilosis as an opportunistic pathogen in raptor pododermatitis in immunocompromised birds maintained under suboptimal husbandry. Mycological work-up, including molecular identification, is therefore warranted in cases of chronic, non-resolving pododermatitis in captive birds of prey.

Kukhar E
Bailina G
Nessipbayeva A
Sattarova R
Turkeyev M

Animals
Candida
Kazakhstan
Phylogeny
Antifungal Agents
Candidiasis
Bird Diseases
Foot Diseases
Dermatitis
Chronic Disease


Molecular analysis and computational modeling reveal temporally separable responses triggered by DENV-induced soluble factors in endothelial cells

Abstract: Dengue virus (DENV) represents a growing global health challenge with billions of people at risk. Severe Dengue (SD), a complication of DENV infection that involves generalized hemorrhage, is driven, at least in part, by endothelial dysfunction. Endothelial dysfunction refers to increased permeability due to inflammation, mechanical injury and/or modification of the genetic program of endothelial cells. Previous work showed that exposure of endothelial cells to conditioned media from DENV-infected cells (CMDV) increased permeability and cellular stiffness, repressed endothelial markers and induced mesenchymal genes. However, the generality, extent, mechanism and ultimate impact of these events in the onset of SD remain elusive. Here, we integrate analysis from in vitro treatment of endothelial cells with media containing UV-inactivated DENV with computational modeling to investigate the key features of CMDV-induced endothelial alterations and their potential impact on endothelial dysfunction. We found that CMDV increased SNA1 and CDH2 expression, while suppressing endothelial genes OCLN and CDH5. Global transcriptomics analysis revealed that CMDV triggered a transient pro-inflammatory response, followed by induction of selected tissue repair genes and matrix remodeling. A non-directed asynchronous network model (NDAM-CMDV) identified IL6 and FN1 as central nodes of DENV-induced endothelial trans-differentiation, providing new molecular insights that predict the evolution of the disease and identify potential therapeutic targets.

Alfaro-García JP
Ramírez-Mejía JM
Rojas-Estevez P
Álvarez-Díaz DA
Fernández GJ
Orozco-Castaño CA
Rodríguez-Rey BA
Gallego-Gómez JC
Vicente-Manzanares M

Dengue Virus
Humans
Endothelial Cells
Computer Simulation
Culture Media, Conditioned
Gene Expression Profiling
Human Umbilical Vein Endothelial Cells


Cardiovascular adjustments during experimentally induced retraction and locomotion in the invasive terrestrial snail Cornu aspersum (Müller, 1774)

Abstract: The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum. We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a "fight-or-flight"-like response.

Pardo-Sarmiento EA
Hernández JP
Buitrago-Ricaurte N
Riveros AJ

Animals
Locomotion
Heart Rate
Snails
Introduced Species


Urate dysregulation (hyperuricemia and gout) among people living with HIV: A protocol for a systematic review and meta-analysis

Abstract: Approximately 39.9 million people are living with HIV worldwide, most in sub-Saharan Africa. Effective antiretroviral therapy has shifted attention to metabolic comorbidities, and emerging evidence links integrase inhibitors such as dolutegravir to elevated serum uric acid, yet the global burden of hyperuricemia and gout in this population is unquantified. This protocol describes a systematic review and meta-analysis of observational studies (cross-sectional, cohort, and case-control) published from inception to May 2026. We will search PubMed/MEDLINE, EMBASE, Web of Science, and CINAHL. Studies involving adults (≥18 years) living with HIV that report the prevalence or incidence of hyperuricemia or gout will be included. Two independent reviewers will screen studies, extract data, and assess risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Checklist and the Newcastle-Ottawa Scale (NOS). Primary outcomes are the pooled prevalence of hyperuricemia and gout in PLHIV. Secondary outcomes include risk factors associated with urate dysregulation (ART regimen, Cluster of Differentiation 4 [CD4] count, viral load, metabolic comorbidities, and HIV duration), and gout as an immune reconstitution inflammatory syndrome (IRIS) manifestation. A random-effects meta-analysis using the DerSimonian-Laird method with Freeman-Tukey double-arcsine transformation for prevalence data will be performed in R software. Heterogeneity will be assessed using the I2 statistic and Cochran's Q test. Subgroup analyses will explore variation by ART class (pre-ART, PI, NNRTI, INSTI/dolutegravir era), geographic region, CD4 category, and study quality. CRD420261360734.

Pitua I
Otto KA
Lwembawo KD
Nantalaga KC
Nampiinga MG
Ndyomugabe M
Okema JN

Humans
Systematic Reviews as Topic
Hyperuricemia
HIV Infections
Gout
Meta-Analysis as Topic
Uric Acid
Prevalence
Risk Factors


Spatiotemporal co-circulation of four dengue serotypes across Mexico, 2020-2025: A space-time scan analysis

Abstract: Mexico has experienced escalating dengue transmission driven by the co‑circulation of four antigenically distinct serotypes (DENV‑1 through DENV‑4). Multi‑serotype transmission is epidemiologically relevant, yet its spatiotemporal patterns at sub‑national resolution remain poorly characterized. We analyzed 103,426 PCR‑confirmed, serotyped dengue cases across 1,547 of 2,471 Mexican municipalities from January 2020 to December 2025. Kulldorff's space‑time scan statistic under a discrete Poisson model was applied independently to each serotype and to all serotypes combined. Co‑circulation was defined as the spatiotemporal overlap of significant clusters from at least two serotypes within the same municipality for ≥ 1 epidemiological week. We identified 159 statistically significant clusters across all serotypes combined. DENV‑3 was dominant (64.4% of cases; annual incidence 59.9/100,000), consistent with the reemergence of a long‑absent serotype. The 2024-2025 season produced a nationally synchronized epidemic across geographically distant regions. Co‑circulation of at least two serotypes occurred in 1,545 municipalities; 217 experienced simultaneous clustering of all four serotypes. Active co‑circulation was present in 275 of 311 study weeks. Mean pairwise temporal overlap ranged from 8.0 to 12.0 weeks, with maximum overlaps of 29-30 weeks. Four‑serotype co‑circulation was documented at municipal resolution, concentrated in the Gulf coast, the Yucatán Peninsula, and northeastern Mexico. The 217 municipalities with simultaneous clustering of all four serotypes may represent areas of epidemiological interest for further investigation. This municipality‑level spatiotemporal framework offers operationally relevant resolution for tracking multi‑serotype activity and supporting serotype‑aware dengue monitoring at sub‑national scale.

Mendoza-Cano O
Trujillo X
Ríos-Silva M
Bricio-Barrios JA
Lugo-Radillo A
Tapia-Vargas R
Venegas-Ramírez J
Ríos-Bracamontes EF
Cuevas-Arellano HB
Cárdenas Y
Aquino-Santos R
Jiménez-Vieyra IA
Uribe-Ramos JM
Benites-Godínez V
Martínez-Díaz TE
López-Rojas M
García-Solórzano A
Murillo-Zamora E

Mexico
Dengue
Dengue Virus
Humans
Serogroup
Spatio-Temporal Analysis
Serotyping


Bacterial vaginosis in early pregnancy and birth outcomes: Evidence from a prospective cohort in the middle belt of Ghana

Abstract: Bacterial vaginosis (BV) is highly prevalent in women of African origin and has been associated with adverse birth outcomes (ABO), particularly preterm birth (PTB). However, evidence from sub-Saharan Africa remains limited, and while a previous study conducted in this area examined the prevalence of BV, its impact on pregnancy outcomes was not assessed. This study assessed the prevalence and risk factors of BV in early pregnancy and examined its association with ABO in the middle belt of Ghana. This analysis was nested within a prospective cohort of pregnant women in the Kintampo North Municipality and Kintampo South District. Pregnant women <20 weeks' gestational age were screened, consented, enrolled and followed through delivery until one year after birth. At enrolment, sociodemographic, behavioural, and obstetric data were collected, along with biological samples, including vaginal swabs for Gram staining and Nugent scoring. BV status was categorized as BV-negative (0-6) or BV-positive (7-10) and ABO included PTB (<37 weeks), low birthweight (LBW < 2.5 kg), and foetal loss. Data were double-entered in REDCap and analysed in R. Associations between BV and ABO were assessed using chi-square tests, and logistic regression was used to identify risk factors for BV. Of 1,180 pregnant women enrolled, 355 (30.1%) were BV-positive. PTB (9.9% vs. 8.7%; p = 0.50), LBW (13.8% vs. 12.0%; p = 0.39), and foetal loss (4.5% vs. 2.8%; p = 0.14) were all higher among BV-positive women, but none reached statistical significance. Younger age and unmarried status were associated with BV. Unmarried women (AOR 1.63; 95% CI: 1.20-2.22) and those reporting one sexual encounter per week (AOR 1.55; 95% CI: 1.01-2.37) had increased odds of BV. BV is highly prevalent in early pregnancy in this Ghanaian cohort, particularly among younger and unmarried women, but was not significantly associated with ABO. Targeted screening among high-risk groups is necessary, and future molecular approaches may better characterise BV subtypes linked to ABO in African settings.

Konadu DG
Owusu-Ofori AK
Dosoo DK
Yidana Z
Ngo GM
Nfum PN
Tetteh RJ
Adu-Gyasi D
Poku-Asante K

Humans
Female
Pregnancy
Vaginosis, Bacterial
Ghana
Prospective Studies
Adult
Pregnancy Outcome
Premature Birth
Risk Factors
Pregnancy Complications, Infectious
Young Adult
Prevalence
Infant, Newborn
Infant, Low Birth Weight


Diagnostic accuracy of automated hematology analyzer abnormal flags for detecting hematological malignancies: A systematic review and meta-analysis

Abstract: Hematological malignancies including leukemia, lymphoma, and myelodysplastic syndromes, are characterized by clonal proliferation of abnormal blood or bone marrow cells. Early and accurate detection is essential for improving treatment outcomes and survival. Automated hematology analyzers generate abnormal flags that may indicate underlying hematologic malignancies; however, their overall diagnostic accuracy has not been comprehensively evaluated. This systematic review and meta-analysis aimed to assess the diagnostic performance of abnormal flags for detecting hematological malignancies. A systematic search of PubMed, PubMed Central, Scopus, ScienceDirect, and Google Scholar was conducted to identify relevant diagnostic accuracy studies. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2) tool. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated using a bivariate random-effects model in Stata version 17.0. Heterogeneity was assessed using the I2 statistic, and subgroup and meta-regression analyses were performed to explore potential sources of variability. Twenty-eight studies met the inclusion criteria. The pooled sensitivity and specificity of abnormal hematology analyzer flags for detecting hematological malignancies were 91% (95% CI: 87%-94%) and 89% (95% CI: 84%-92%), respectively, indicating good diagnostic accuracy. Significant heterogeneity was observed across studies (I2 > 50%). Meta-regression analysis identified the type of abnormal flag as a significant source of heterogeneity in sensitivity (p < 0.001), whereas both the type of abnormal flag and the analyzer platform significantly influenced specificity. Automated hematology analyzer abnormal flags showed promising diagnostic performance. However, substantial heterogeneity and differences in analyzer platforms, flag types, and reference standards reduce the certainty and generalizability of pooled estimates. Nevertheless, these findings support the use of abnormal hematology analyzer flags as an effective initial screening tool in routine laboratory practice, particularly in resource-limited settings where rapid and cost-effective diagnostic support is essential. Systematic review registration PROSPERO (CRD42024601908).

Mulatie Z
Eshetu B
Habtamu A
Desale S
Sebsibe S
Erkihun Y
Kassa Y
Gessese T
Alebachew M
Shimeles M
Feyisa MS
Berta DM

Humans
Hematologic Neoplasms
Sensitivity and Specificity
Hematology

Journal Article
Systematic Review
Meta-Analysis


Mixed feelings: Unintended consequences of HIV outreach care in Zimbabwe

Abstract: Decentralization of antiretroviral therapy (ART) brought treatment to millions of people in Sub-Saharan Africa. However, the implications of such decentralization are still not fully understood. The study included 60 semi-structured interviews with community leaders, healthcare providers, patients, and community members served by a rural mission hospital in Zimbabwe, conducted in January-March 2019. Interviews were transcribed and translated into English and coded using an iterative codebook. Coded extracts were grouped into themes and categories, systematically using QDA Miner qualitative analysis software. The study reveals that treatment-for-all policies and decentralization of ART have indeed improved access to care (as experienced by the study participants). However, the study shows that these policies also had unintended negative consequences. Stigma and complex social relations significantly affect the practices and experiences of ART outreach care, for both patients and healthcare providers, and may hamper attempts to reduce stigma as well as increase physical and social barriers to accessing ART. The study's results highlight the need to understand the consequences of the decentralization of HIV care, as well as the barriers and facilitators associated with ART outreach in order to improve quality of care and provide true accessibility to HIV care for all.

Gluskinos N
Maposhere C
Kufakurinani U
Hove G
McCarty K
Katzenstein D
Rosenthal A

Zimbabwe
Humans
HIV Infections
Health Services Accessibility
Female
Male
Social Stigma
Health Personnel
Adult


Reproducibility of fetal global longitudinal strain measured with speckle tracking echocardiography using a fixed cardiac cycle

Abstract: Fetal speckle tracking echocardiography is an ultrasound-based technique used to assess myocardial velocity and deformation of the fetal heart. Despite its potential, the method has not yet been integrated into routine pregnancy care, partly due to concerns about inconsistent reproducibility. This study aimed to evaluate the intra- and inter-observer reproducibility of global longitudinal strain measurements derived from a fixed fetal cardiac cycle, using speckle tracking echocardiography. Healthy women with singleton pregnancies were enrolled during the second trimester. From enrolment until delivery, four-chamber view clips of the fetal heart were acquired every four weeks. For intra-observer reproducibility, a single observer analyzed the same heart cycle in one DICOM clip twice for global longitudinal strain in the left and right ventricles, with a minimum interval of two weeks between assessments in a blinded manner. For inter-observer reproducibility, two independent observers analyzed the same cardiac cycle within one DICOM clip. A total of 124 women were included, yielding 632 ultrasound clips. Intra-observer reproducibility was poor to moderate for global longitudinal strain for the right and left ventricles. Inter-observer reproducibility demonstrated moderate to good reproducibility for global longitudinal strain in both ventricles. The reproducibility was generally higher in the left ventricle than in the right, and the highest reproducibility was observed before 32 weeks of gestation. In conclusion, speckle tracking echocardiography during pregnancy showed variable reproducibility of strain analysis when performed on a fixed cardiac cycle, with more consistent results in the left ventricle. These findings support the potential utility of fetal speckle tracking echocardiography, while highlighting the need for further refinement of reproducibility before clinical implementation.

Meireson E
de Vet C
van Laar JOEH
Mussche P
Roelens K
van Oostrum NHM

Humans
Female
Pregnancy
Global Longitudinal Strain
Echocardiography
Reproducibility of Results
Ultrasonography, Prenatal
Fetal Heart
Adult
Heart Ventricles
Observer Variation


Catastrophe mechanism and early warning indicators of seepage erosion-induced water inrush in karst cavities

Abstract: Seepage-erosion-induced water inrush in karst cavities is a typical form of water-inrush disaster in karst tunnels. It is governed not only by the spatial distribution of karst cavities and hydraulic recharge conditions, but also by the particle-size gradation and composition of the cavity fill. During seepage erosion, fill particles are progressively transported by flowing water, which may trigger a sudden water-inrush catastrophe. To reveal the catastrophe mechanism and establish early-warning indicators, this study employs the Smoothed Particle Hydrodynamics (SPH) method to simulate the evolution of seepage-erosion-induced water inrush under different particle-size gradations, cavity confining stresses, and seepage velocities. The inflection point of the cumulative particle loss rate is used as an indicator of catastrophic transition. The relationships among particle-size gradation, confining stress, seepage velocity, and particle loss rate at the transition point are then analyzed to determine early-warning thresholds. The results show that fill-particle loss is positively correlated with both seepage velocity and confining stress. When the content of fine particles, such as rock cuttings and fine sand, exceeds 60%, the inflection point corresponds to a seepage velocity of 1.6 m/s and a confining stress of 2.6 MPa, with an early-warning particle-loss range of 8%-15%. When the content of coarse particles, such as coarse sand and gravel, exceeds 40%, the inflection point corresponds to a seepage velocity of 3.0 m/s and a confining stress of 4.5 MPa, with an early-warning particle-loss threshold of approximately 45%.

Soil Erosion
Particle Size
Hydrodynamics
Disasters
Water Movements
Models, Theoretical
Water


Heat stress-induced photosynthetic impairment and autophagy modulation in Paris polyphylla var. yunnanensis: A physiological and molecular Perspective

Abstract: High temperature is one of the major environmental stressors that severely affects plant growth. Paris polyphylla var. yunnanensis, a traditional Chinese herbal medicine, is sensitive to high temperature. However, the underlying mechanisms of its response to high temperature remain unclear. In this study, we investigated the physiological and proteomic change of P. polyphylla var. yunnanensis under different treatments (25°C, 30°C, 35°C, 40°C). Our results showed that high temperature directly impaired photosynthesis and disrupted metabolism, evidenced by reduced chlorophyll and photosynthetic rate, as well as accumulated proline and increased conductivity. A total of 893 differentially expressed proteins (DEPs) were identified, with significant changes in the expression levels of enzymes associated with protein processing and synthesis. Additionally, the expression levels of key proteins involved in the circadian pathway and the glutathione pathway were also notably upregulated. Dynamic changes in the endocytosis and autophagy-related proteins ATG3 and ATG8C were also observed, suggesting that these processes may play a significant protective role under high-temperature stress. Overall, this study provides an important starting point for improving the heat tolerance of P.polyphylla var. yunnanensis through genetic engineering.

Autophagy
Photosynthesis
Heat-Shock Response
Plant Proteins
Melanthiaceae
Gene Expression Regulation, Plant
Hot Temperature
Proteomics


Functional node layout in Metroidvania game worlds: A complex network analysis

Abstract: This study investigates how the spatial structure of Metroidvania game worlds relates to the layout of key functional nodes. Using Hollow Knight, Prince of Persia: The Lost Crown, and Blasphemous 2 as case studies, the maps were transformed into graph structures based on spatial data compiled from gameplay observation, in-game maps, community maps, and verification through gameplay videos. On the basis of this graph representation, the study adapts the Nearest Neighbor Index by replacing Euclidean distance with network shortest-path distance in order to evaluate the distribution patterns of save points, teleport points, and boss points. It further employs multi-source k-hop reachability analysis to measure service coverage and redundancy. Finally, closeness centrality and betweenness centrality are calculated on the full network, and Spearman rank correlation is used to test the association between functional areas and centrality. The results reveal clear differences in the structural roles of functional nodes across the three games. In Hollow Knight and The Lost Crown, save points are relatively dispersed, weakly coupled with centrality, and function as a distributed safety net. In Blasphemous 2, save points exhibit higher small-radius coverage and redundancy and are more strongly aligned with central positions, indicating a hub-like stronghold structure. Teleport systems likewise reflect different design strategies, ranging from exploration-oriented sparse layouts to later-stage mobility optimization. Boss points in all three games generally remain structurally isolated, showing low overlap and weak centrality association. These findings suggest that differences in the placement of save points, teleport points, and boss points reflect distinct structural design strategies, and that network analysis can provide a quantitative basis for evaluating and optimizing such layouts in level design.

Bao GG
Weng B
Ding L
Du Q
Zang Y
Wang J
Yan F


Personality traits have an effect on pain-related psychological variables in patients with chronic low back pain

Abstract: An association between personality factors and pain experience has been investigated. However, the direct contributions of personality traits by the Maudsley Personality Inventory to clinical pain outcomes in patients with chronic pain remain unclear. The Maudsley Personality Inventory is a self-report questionnaire used to assess extroversion, neurotic tendencies, and lying or exhibitionistic tendencies. The present study aimed to investigate whether personality traits influenced with the pain-related psychological variables in patients with chronic secondary low back pain (CLBP). One hundred fifteen consecutive outpatients with CLBP were included. Personality traits were measured by using the Maudsley Personality Inventory to assess extroversion, neurotic tendencies, and lying or exhibitionistic tendencies. The association of Maudsley neurotic tendency score and pain-related variables was analyzed and then performed a path analysis. Eleven patients (9%) were the biased persons with frequent lying. The pain-related variables showed no significant differences between the persons with frequent lying and those with normal. The Maudsley neurotic tendency score was significantly associated with Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, Pain Self-Efficacy Questionnaire, Athens Insomnia Scale, and EuroQol-5 Dimensions-3 level. The unstandardized coefficients for Maudsley neurotic tendency score were small, compared to pain-Numerical Rating Scale in each outcome. These results suggest the presence of neurotic tendency could have an impact on the health outcomes in patients with CLBP, but the impact was small.

Hayashi K
Miki K
Fukushima Y
Iwai M
Shiro Y
Tetsunaga T
Takasusuki T
Hosoi M
Yukioka M
Okada S

Humans
Low Back Pain
Female
Male
Middle Aged
Personality
Chronic Pain
Adult
Surveys and Questionnaires
Personality Inventory
Pain Measurement
Aged


Case-matched retrieval improves textual alignment of LLM-generated radiology impressions

Abstract: Radiology impressions guide clinical care. Large Language Models (LLMs)-drafted impressions can drift into generic, off-style text. Retrieval-augmented generation (RAG) enables context-aware few-shot prompting during inference. This retrospective IRB-approved study included 11,998 CT pulmonary angiography (CTPA) reports. We built a retrieval bank from 11,399 reports and reserved 599 reports for testing. GPT-4o and LLaMA 3.1-70B generated impressions from the "findings" section using three setups: zero-shot, fixed random few-shot, and dynamic retrieval-selected few-shot (top-k semantic matches; k = 3/5/10). We ran temperatures 0, 0.7, 1. We scored outputs against the original impressions with ROUGE and BERTScore F1, report mean scores with 95% confidence intervals, and tested for statistical significance using Wilcoxon signed-rank test. Dynamic retrieval-based few-shot prompting outperformed zero-shot and fixed few-shot prompting across all configurations (all p < 0.05). The highest scores were observed at temperature 0 and k = 10. ROUGE-1 F1 increased to 0.44-0.47 for GPT-4o and 0.37-0.50 for LLaMA, versus 0.35-0.37 and 0.25-0.37, respectively, in zero-shot prompting. Lower temperature and larger k were associated with higher similarity scores. Dynamic, case-matched retrieval improved alignment of LLM-generated CTPA impressions with reference impressions on automated text-similarity metrics. Scores remained moderate, and radiologists' verification is still required before clinical deployment.

Sorin V
Collins JD
Hahn LD
Bratt AK
Klang E
Korfiatis P

Large Language Models
Humans
Retrospective Studies
Information Storage and Retrieval


Incremental diagnostic yield of bone scintigraphy after standard radiologic imaging in patients with fall trauma at a Level I trauma center

Abstract: This study aimed to evaluate the incremental diagnostic yield of bone scintigraphy (BS) performed after standard radiologic imaging (SRI) modalities, including radiography, computed tomography, and magnetic resonance imaging, in patients with fall trauma presenting to a Level I trauma center. Three hundred eight patients with fall trauma who underwent BS after SRI were retrospectively enrolled. The presence and number of bone injuries across six skeletal regions were evaluated using both SRI and BS. Bone injuries were evaluated according to three imaging-based categories: SRI alone, SRI - /BS + , and SRI + BS. Imaging-derived bone parameters included the total number of regions with bone injuries, the total number of injured bones, and the Imaging Bone Index (IBI) score. Correlations between these imaging-derived bone parameters and four trauma scores were analyzed, and differences in imaging-derived bone parameters were examined according to the cutoff values of each trauma score. The imaging-derived bone parameters in the SRI + BS category were significantly higher than those in the SRI alone category. Imaging-derived bone parameters in both the SRI alone and SRI + BS categories showed significant correlations with all trauma scores, with significantly stronger correlations for the total number of injured bones and IBI scores in the SRI + BS category. Patients with severe trauma exhibited significantly higher imaging-derived bone parameters in the SRI - /BS+ category. Performing BS after SRI provided incremental diagnostic yield by detecting additional bone injuries not identified on preceding SRI and yielded quantitative imaging-derived bone parameters associated with trauma severity in this Level I trauma center cohort of patients with fall trauma.

Humans
Female
Accidental Falls
Trauma Centers
Male
Retrospective Studies
Radionuclide Imaging
Bone and Bones
Middle Aged
Adult
Tomography, X-Ray Computed
Aged
Magnetic Resonance Imaging


Fecal carriage of ESBL and Carbapenemase-producing Enterobacteriaceae, and its associated factors among hospital and non-hospital janitors at the University of Gondar, Northwest Ethiopia: A comparative cross-sectional study

Abstract: Extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (CPE) pose a critical public health threat. Janitors are routinely exposed to contaminated environments and may act as a reservoir for these resistant bacteria, particularly in resource-limited settings like Ethiopia, where data on this subject are scarce. The aim of this study was to assess fecal carriage rates of ESBL-PE, CPE and its associated factors among hospital and non-hospital janitors at the University of Gondar (UoG), Northwest Ethiopia. A comparative cross-sectional study was conducted from June 15 to September 25, 2025, at the UoG. A total of 385 janitors (203 hospital and 182 non-hospital) were selected using stratified and simple random sampling techniques. Data on socio-demographic and associated factors were collected using a semi-structured questionnaire. Stool samples were collected aseptically and cultured on MacConkey agar. Antimicrobial resistance (AMR) patterns were determined by the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines. The ESBL and carbapenemase production were confirmed using the combination disk and modified Carbapenem inactivation methods, respectively. Quality control was ensured by using standard reference strains. Data analysis was performed using SPSS version 27.0, employing chi-square tests and logistic regression. A p-value of <0.05 was considered statistically significant. Among the 385 stool samples, a total of 416 Enterobacteriaceae isolates were recovered, 229 from hospital janitors and 187 from non-hospital janitors. The overall fecal carriage rates among janitors were 83 (21.6%) for ESBL-PE and 14 (3.6%) for CPE. Hospital janitors had significantly higher carriage rate than non-hospital janitors for both ESBL-PE (28.6% vs. 13.7%, p < 0.001) and CPE (5.9% vs. 1.1%, p = 0.012), respectively. Escherichia coli was the predominant ESBL-producer. Significant risk factors identified for ESBL-PE colonization included lack of hand hygiene at home, history of antibiotic use, and urinary tract infection for hospital janitors, and age ≥ 40 years and history of non-prescription antibiotic use were for non-hospital janitors. This high carriage rates of ESBL-PE and CPE, identify janitors as a significant reservoir for resistant bacteria. We recommend integrating janitors into national AMR surveillance programs and strengthening infection prevention and control and antimicrobial stewardship training.

Zayede A
Wondimeneh Y
Biset S
Gizachew M

Ethiopia
Cross-Sectional Studies
Humans
beta-Lactamases
Feces
Carbapenem-Resistant Enterobacteriaceae
Enterobacteriaceae
Enterobacteriaceae Infections
Bacterial Proteins
Male
Female
Adult
Anti-Bacterial Agents
Microbial Sensitivity Tests


In vitro and in vivo antibacterial activities and phytochemical screening of 80% methanol extract from Ehretia cymosa leaves

Abstract: Antibiotic resistance has emerged as one of the most urgent global health threats, undermining the effective treatment of bacterial infections. In response, scientific interest is increasingly focused on identifying natural and effective antimicrobial agents derived from medicinal plants. In Ethiopia, Ehretia cymosa (E. cymosa) is traditionally used to treat wound infections, fever, gastric ulcers, dysentery, and toothache. However, there is limited scientific evidence to support these traditional claims. Hence, the present study aimed to evaluate the in vitro and in vivo antibacterial activities and to screen the phytochemical profile of the 80% methanol extract of E. cymosa leaves. The air-dried and powdered leaves of E. cymosa were extracted using cold maceration with 80% methanol. The antibacterial activity of the crude extract was tested using the disk diffusion method against selected bacterial pathogens commonly associated with infections. An in vivo model of burn followed by infection was established in mice. Qualitative phytochemical screening was also performed. One-way analysis of variance followed by Tukey's post hoc multiple tests was used to compare the means of all parameters. The leaves of E. cymosa demonstrated significant antibacterial activity (p < 0.001) against the tested bacterial strains in a dose-dependent manner compared with the control. The minimum inhibitory concentration ranged from 6.25 to 75 mg/mL, while the minimum bactericidal concentration against P. aeruginosa and E. coli was 200 mg/mL. In the in vivo model, the extract resulted in faster wound contraction and a shorter epithelialization period against S. aureus than against P. aeruginosa. The plant leaf is also rich in flavonoids, terpenoids, and tannins. The 80% methanol extract of E. cymosa leaves exhibited antibacterial activity in vitro and in vivo, which corroborates the traditional use of the leaves against infectious diseases. Further studies involving the isolation and characterization of the active compounds are recommended.

Mekonnen E
Edessa D
Weldegebreal F
Aklog A
Gashaw T

Plant Leaves
Anti-Bacterial Agents
Plant Extracts
Animals
Methanol
Mice
Microbial Sensitivity Tests
Phytochemicals


Ensemble learning-based online sequential pre-interference extreme learning for concept drifting and class imbalanced data streams

Abstract: With the rapid development of data-driven technologies, real-time data streams not only exhibit concept drift but are also frequently accompanied by class imbalance problems. To address these challenges, this paper proposes an online sequential pre-interference layer extreme learning machine (OS-PIELM). The proposed model introduces a pre-interference layer between the input layer and hidden layer of the original OS-ELM to enhance nonlinear feature representation through kernel-like transformation of sequential data, thereby improving the discriminative ability of different classes. Furthermore, an adaptive forgetting factor and a Gmean-based concept drift detection mechanism are incorporated into OS-PIELM, together with a dynamic weighting strategy. These components enable the model to effectively handle class imbalance in data streams and enhance its sensitivity to concept drift. Finally, an online ensemble learning framework is constructed with OS-PIELM as the base classifier to further improve the robustness of the proposed method. Extensive experiments on nine synthetic datasets and two real-world datasets demonstrate that the proposed method can effectively address class imbalance in data streams and improve concept drift detection performance.

Extreme Learning Machines
Ensemble Learning
Classification Algorithms
Algorithms
Soft Computing


A multiplex dual-probe RT-LAMP assay for rapid subtype-specific detection of respiratory syncytial virus A and B

Abstract: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections, particularly in infants, older adults, and immunocompromised individuals. RSV is classified into two major subtypes, RSV A and RSV B, which co-circulate seasonally and exhibit genetic variability, highlighting the need for rapid and subtype-specific diagnostic methods. Although reverse transcription quantitative PCR (RT-qPCR) is the reference standard for RSV detection, its reliance on complex instrumentation limits its applicability in decentralized testing settings. In this study, we developed and evaluated a probe-based reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection and differentiation of RSV A and RSV B. The assay incorporates a dual-probe strategy, employing an assimilating probe for RSV A detection to ensure robust signal generation under multiplex conditions, and hybridization-based TaqMan-style probes (HyTaq probes) for RSV B detection and for an internal control targeting the human ACTB gene to ensure reaction validity. Analytical performance was assessed using serially diluted RSV positive clinical specimens and plasmid standards. Clinical performance was evaluated using 91 RSV A positive specimens, 97 RSV B positive specimens, and 120 RSV negative specimens, as defined by the reference diagnosis. The RSV A and RSV B RT-LAMP assays demonstrated sensitivities of 92.31% and 98.97%, respectively, with a specificity of 100% for both targets. No cross-reactivity was observed with a panel of common respiratory viruses. These results indicate that the proposed dual-probe RT-LAMP assay provides a rapid and specific approach for subtype-specific RSV detection, with potential applicability in decentralized diagnostic settings pending further validation.

Humans
Nucleic Acid Amplification Techniques
Respiratory Syncytial Virus Infections
Respiratory Syncytial Virus, Human
Sensitivity and Specificity
Molecular Diagnostic Techniques
Rapid Diagnostic Tests
RNA, Viral


Herbal medicine use disclosure, database-flagged potential herb-drug interactions, and inter - interaction database concordance among patients with non-communicable diseases in Vietnam: A multicenter cross-sectional study

Abstract: The widespread use of herbal medicines in clinical practice, particularly in Southeast Asia, presents significant challenges for medication safety management, notably regarding interactions between herbs and conventional drugs. Current drug interaction screening tools demonstrate substantial gaps in documenting herb-drug interactions, especially for regionally specific medicinal plants, creating potential risks for patients receiving concurrent therapies. (1) to identify the prevalence of potential herb-drug and herb-herb interactions and the disclosure rate of HM use in patients with NCDs; and (2) to assess the consistency of interaction information across commonly used drug interaction databases. An observational study enrolled 658 patients with non-communicable diseases from two Vietnamese tertiary care facilities. Structured interviews captured herbal medicine utilization patterns, disclosure practices, and specific botanical preparations used. Potential herb-drug and herb-herb interactions were systematically evaluated using four databases: Micromedex®, UpToDate Lexicomp Drug Interactions, Medscape Drug Interaction Checker, and Stockley's Herbal Medicines Interactions. Inter-database agreement was assessed using Fleiss' kappa statistics. 48.6% of participants reported active herbal medicines use, with 96% failing to disclose this to their healthcare providers. Potential interactions were identified in 31.3% of herbal medicine users, representing 15.2% of the total cohort. Database concordance was remarkably poor, with only 0.7% of interactions consistently documented across all four resources (Fleiss' κ = -0.0653; p < 0.001). Multiple indigenous medicinal plants commonly used by patients were absent from all evaluated databases. The substantial prevalence of undisclosed herbal medicine use, alongside inadequate representation in drug interaction databases, represents a critical gap in medication safety infrastructure. These findings demonstrated the necessity for integrating herbal medicine assessment into routine care, enhanced provider training, and expansion of clinical decision support systems to include region-specific botanical data for populations using concurrent traditional and conventional therapies.

Phan ADT
Vo TH
Luu TNN
Ngo HTT
Heinrich M
Kongkaew C

Herb-Drug Interactions
Humans
Vietnam
Cross-Sectional Studies
Noncommunicable Diseases
Female
Databases, Factual
Middle Aged
Herbal Medicine
Plants, Medicinal
Adult
Aged
Disclosure

Journal Article
Multicenter Study
Observational Study


Barriers and levers to using an app for motor function assessment by therapists in hospitals: A qualitative study of the MFM-Play app

Abstract: The Motor Function Measure (MFM) is an important evaluation tool used to monitor the progression of most neuromuscular diseases. However, the MFM is subject to inter-rater variability, and patients must produce their best effort, which can be difficult for children. In response to these issues, we developed a digital app named MFM-Play, designed to optimise completion of the MFM in a fun manner. The objective of this study was to explore barriers and levers to the MFM-Play's use by therapists. We conducted a qualitative study with rehabilitation professionals who had tested the app in a previous reliability study. Individual interviews based on the Technology Acceptance Model were followed by a focus group based on the interview results. Thematic analysis was performed on transcripts. Seven therapists participated in the interviews and seven others in the focus group. The results revealed the multi-dimensional features related to adopting the MFM-Play app. Barriers related to ease of use, training and organisational constraints were identified, and were partly due to the additional mental burden of learning to use the technology. However, therapists who were at ease with the digital tool found it useful for their practice. The app also modified patient-therapist dynamics, fostering greater patient autonomy, but sometimes disrupted therapists' habits, by calling into question assessment methods. The MFM-Play app offers considerable practical and efficiency benefits; however, its successful adoption depends on overcoming technical, organisational, and user-specific barriers. This involves providing support for the change in the therapist's stance within the triadic patient-therapist-tablet relationship.

Vincent-Genod D
Verroul M
Rippert P
Tachibana S
Vuillerot C
MFM-Play Study Group

Humans
Mobile Applications
Qualitative Research
Focus Groups
Female
Male
Hospitals
Physical Therapists
Neuromuscular Diseases
Adult


Cognitive-behavioral therapy focused on inhibitory learning, for adults with avoidant/restrictive food intake disorder (ARFID): Study protocol of a prospective study

Abstract: Currently, there are no evidence-based treatments available for adults with avoidant/restrictive food intake disorder (ARFID). The present paper describes the design of a study evaluating a cognitive-behavioral therapy (CBT) protocol for adults with ARFID, with a focus on exposure using inhibitory learning principles. This multicenter study uses a prospective, uncontrolled, repeated-measures design. A total of 120 adults (aged ≥ 18 years) with ARFID will be included via 11 participating treatment centers throughout the Netherlands. Participants will receive a manualized treatment of 25 weekly sessions. Assessments will be conducted at baseline, post-treatment, and at 1- and 12-month follow-ups. The primary outcome is ARFID severity, measured by the Pica, ARFID, and Rumination Disorder Interview (PARDI). Session-level measures of fear and expectancies will be collected throughout the treatment to explore potential mechanisms of change. Treatment effects will be examined across ARFID profiles and comorbid disorders. This is the first large-scale study to investigate an outpatient CBT program for adults with ARFID. By examining outcomes across ARFID profiles and exploring underlying mechanisms of change, the findings are expected to inform treatment refinement and provide a foundation for future controlled trials. The study has been preregistered in AsPredicted (#212,212) and the trial was registered in the Overview of Medical Research in the Netherlands (NL-OMON6121).

Masereel M
Cardona Cano S
Tran TD
de Jonge M
Dumont E
van Elburg AA
Mulkens S

Avoidant Restrictive Food Intake Disorder