Nevin Manimala

Brief Bioinform. 2026 Jan 7;27(1):bbaf713. doi: 10.1093/bib/bbaf713.

ABSTRACT

RNA performs a variety of functions within cells and is implicated in various human diseases. Because druggable proteins occupy a small portion of the genome, considerable interest has been increasing in developing drugs targeting RNAs. Thus, precise prediction of small-molecule binding sites across different classes of RNAs is important. In this study, a lightweight deep learning program for predicting RNA-drug binding sites, called compound binding site prediction for RNA (CoBRA), is introduced. Our approach utilizes residue-level embeddings derived from a pre-trained RNA language model, without relying on any structural information. These embeddings encapsulate the contextual and statistical properties of each nucleotide and are used as input for a multi-layer perceptron classifier that performs binary classification of binding nucleotides. The model was trained using the TR60 and HARIBOSS datasets and tested on four independent benchmark sets. The performance of CoBRA demonstrates a relative improvement of 22.1% in the Matthew correlation coefficient and a 45.6% increase in sensitivity compared to existing state-of-the-art RNA-ligand binding site prediction methods that utilize structural information. These results demonstrate that sequence-based language model embeddings, which do not require explicit coordinate or distance information, can match or outperform structure-based methods. This makes it a flexible tool for predicting binding sites across diverse RNA targets.

PMID:41520231 | DOI:10.1093/bib/bbaf713

Brief Bioinform. 2026 Jan 7;27(1):bbaf711. doi: 10.1093/bib/bbaf711.

ABSTRACT

Statistical deconvolution methods offer a powerful solution for estimating cell-type-specific (CTS) profiles from readily available bulk tissue data. However, a critical limitation of existing methods is that they require the knowledge of cell type proportions of individuals in the bulk data. While the ground truth of cell type proportions in bulk samples are unknown, those methods use the estimated proportions to approximate the truth, which potentially introduces additional uncertainties in the inferred CTS profiles. To address this challenge, we propose Uncertainty-aware Bayesian Deconvolution (UBD) to incorporate uncertainty in cell type proportion estimates. By explicitly modeling the uncertainty in the initial estimates, UBD refines cell type proportions and estimates sample-level CTS data simultaneously. We show that UBD can improve the estimates of CTS profiles through extensive simulations. We further demonstrate the utility of UBD to reveal more CTS signals in its applications to two real datasets.

PMID:41520227 | DOI:10.1093/bib/bbaf711

Croat Med J. 2026 Jan 5;66(6):419-428.

ABSTRACT

AIM: To assess health care professionals’ knowledge and opinions regarding extracorporeal membrane oxygenation (ECMO) use, training, standards, and resource availability.

METHODS: This cross-sectional study employed an online self-administered survey to evaluate health care professionals’ knowledge and opinions concerning ECMO procedures. The survey consisted of multiple-choice and open-ended questions inquiring about demographics, ECMO practices, training and certification experiences, ECMO use during the COVID-19 pandemic, and obstacles to ECMO implementation.

RESULTS: The study enrolled 89 health care professionals from 12 countries. The respondents were most frequently from Kazakhstan (67.4%), Turkey (5.6%), Croatia (5.6%), and Ukraine (5.6%). Notably, 61.8% of respondents supported ECMO procedures performed by certified specialists. The respondents believed that the main ECMO indications were respiratory failure (83.1%), cardiopulmonary failure (69.6%), heart and lung transplantation (64.1%), and cardiogenic shock (58.4%). Major obstacles to ECMO implementation were reported to be high costs (53.9%), inadequately qualified staff (52.8% for physicians, 41.6% for nurses), and restricted availability of ECMO devices (42.7%).

CONCLUSION: The findings emphasize the need for standardized training, wider availability of ECMO standards, and efforts to address resource-related barriers to ECMO access. Our results primarily reflect practices in Kazakhstan and should be interpreted in light of the study’s restricted geographical coverage.

PMID:41520203

Croat Med J. 2026 Jan 5;66(6):390-398.

ABSTRACT

AIM: To examine the associations between marital status, place of residence, self-reported health status, quality of life, and physical activity among older adults during the COVID-19 pandemic.

METHODS: This cross-sectional study enrolled 962 participants aged 65 and older, surveyed between March 2020 and May 2023. Respondents were categorized according to marital status (married/living with a partner, single, divorced, widowed) and place of residence (own home vs nursing home). Standardized instruments were used: the Short Form Health Survey-36 for health status, the Personal Well-being Index for quality of life, and the Croatian short version of the International Physical Activity Questionnaire.

RESULTS: Respondents who were married or living with a partner reported significantly higher levels of physical activity, better physical and mental health, and greater life satisfaction than single, divorced, or widowed respondents (P<0.001). Community-dwelling respondents scored significantly higher on most health and quality-of-life indicators than nursing home residents, except for perceived future security.

CONCLUSION: Marital status and living arrangements significantly affected the self-perceived health, physical activity, and quality of life of older adults during the COVID-19 pandemic. The results emphasize the importance of social support and residential context in promoting healthy aging.

PMID:41520200

Inflamm Bowel Dis. 2026 Jan 11:izaf313. doi: 10.1093/ibd/izaf313. Online ahead of print.

NO ABSTRACT

PMID:41520196 | DOI:10.1093/ibd/izaf313

J Am Med Inform Assoc. 2026 Jan 11:ocaf230. doi: 10.1093/jamia/ocaf230. Online ahead of print.

ABSTRACT

BACKGROUND: Despite rapid integration into clinical decision-making, clinical large language models (LLMs) face substantial translational barriers due to insufficient structural characterization and limited external validation.

OBJECTIVE: We systematically map the clinical LLM research landscape to identify key structural patterns influencing their readiness for real-world clinical deployment.

METHODS: We identified 73 clinical LLM studies published between January 2020 and March 2025 using a structured evidence-mapping approach. To ensure transparency and reproducibility in study selection, we followed key principles from the PRISMA 2020 framework. Each study was categorized by clinical task, base architecture, alignment strategy, data type, language, study design, validation methods, and evaluation metrics.

RESULTS: Studies often addressed multiple early stage clinical tasks-question answering (56.2%), knowledge structuring (31.5%), and disease prediction (43.8%)-primarily using text data (52.1%) and English-language resources (80.8%). GPT models favored retrieval-augmented generation (43.8%), and LLaMA models consistently adopted multistage pretraining and fine-tuning strategies. Only 6.9% of studies included external validation, and prospective designs were observed in just 4.1% of cases, reflecting significant gaps in translational reliability. Evaluations were predominantly quantitative only (79.5%), though qualitative and mixed-method approaches are increasingly recognized for assessing clinical usability and trustworthiness.

CONCLUSION: Clinical LLM research remains exploratory, marked by limited generalizability across languages, data types, and clinical environments. To bridge this gap, future studies must prioritize multilingual and multimodal training, prospective study designs with rigorous external validation, and hybrid evaluation frameworks combining quantitative performance with qualitative clinical usability metrics.

PMID:41520192 | DOI:10.1093/jamia/ocaf230

Global Spine J. 2026 Jan 10:21925682251412809. doi: 10.1177/21925682251412809. Online ahead of print.

ABSTRACT

Study DesignRetrospective Database Study.ObjectivesAnterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are common procedures performed for cervical spondylosis. Sparse data exists comparing the utilization and reimbursement rates associated with these procedures. This study seeks to compare Medicare utilization of single- and multilevel ACDF to CDA between 2011 and 2021. Additionally, this study evaluates Medicare reimbursement rate changes for ACDF with structural allograft, ACDF with cage, and CDA between the years 2016 and 2021.MethodsThis study used the publicly available Medicare National Summary Data Files to aggregate annual utilization and reimbursement rates for ACDF procedures as well as CDA procedures based on Current Procedural Terminology codes. Reimbursement rates were adjusted for inflation through use of the U.S. Bureau of Labor Statistics’ 2021 Consumer Price Index. Changes in reimbursement rates and utilization were calculated and compared between procedures.ResultsIn 2011, 27 974 single-level ACDF procedures were performed on Medicare Part B patients compared to 34 683 performed in 2021. This represents a growth in procedure utilization of 24% over the study period. Over the course of the same study period CDA procedures grew by 1087.3%, from 118 in 2011 to 1401 in 2021. Throughout the reimbursement study period, Medicare reimbursements per case for single-level CDAs had an average annual percent change of 9.96%, rising from $1636 in 2016 to $2779 in 2021. Reimbursement per case for single-level ACDF with allograft had an average annual change of -1.25%, falling from $3408 in 2016 to $3206 in 2021. Medicare reimbursement per case for single-level ACDF with cage had an average annual change of 1.19%, from $3379 in 2017 to $3547 in 2021.ConclusionAll procedures saw an increase in utilization throughout the study period, with CDAs showing significant growth within the Medicare population. While the reimbursement for ACDFs remained relatively constant, the reimbursement for CDAs demonstrated a moderate increase.

PMID:41520188 | DOI:10.1177/21925682251412809

HGG Adv. 2026 Jan 10:100566. doi: 10.1016/j.xhgg.2026.100566. Online ahead of print.

ABSTRACT

Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and 4 population backgrounds (African (5%), Asian (7%), European (85%), and Hispanic (3%)). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA, CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6, DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 loci were derived from non-European populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions (DOCK4, MAGI2) and neuronal signaling (CCK, UGDH, SLC01A2). Integrative druggability analyses identified 11 druggable candidate gene targets linked to pathways involved in mood disorders as well as known antihypertensive drugs. Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.

PMID:41520179 | DOI:10.1016/j.xhgg.2026.100566

Rheumatology (Oxford). 2026 Jan 10:keag016. doi: 10.1093/rheumatology/keag016. Online ahead of print.

ABSTRACT

OBJECTIVES: Several studies reported an association between Sjögren’s disease (SjD) and inclusion body myositis (IBM). However, the potential specificities of IBM when associated with SjD have been poorly investigated. Here, we compared the muscular inflammatory infiltrates between IBM patients with or without associated SjD.

MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded muscle biopsies of patients with IBM, associated with SjD (IBM-SjD) and sporadic (sIBM) forms, from 6 French expert centers, were collected. Imaging mass cytometry (IMC) multiplex immunostaining (34 markers) was used to quantify and analyze inflammatory infiltrate composition. Supervised and unsupervised descriptive and comparative analyses were performed.

RESULTS: Fourteen IBM-SjD and 7 sIBM muscle samples were analyzed. No statistically significant difference was encountered but some trends were pointed. IBM-SjD samples had a broader inflammatory infiltrate surface (median 4.8%, IQR: 1.4-8.6) than sIBM samples (median 1.6% IQR: 1.2-2.4). In both groups, the main inflammatory cells in muscle infiltrate were primarily macrophages and T cells. However, the proportion of plasma cells (14.7% IQR: 5.4-24.6 vs 8.5% IQR: 4.6-9.8) and B cells (3.1% IQR: 0.4-5.6 vs 0.5% IQR: 0.0-3.2) were higher in IBM-SjD patients.

CONCLUSION: Using IMC on muscle biopsies, IBM-SjD and sIBM patients share common histological features, but there are notable distinctions (more extensive infiltrate, high numbers of B cells and plasma cells in IBM-SjD). These observations were exploratory and based on a small number of patients. but may suggest IBM-SjD has distinct SjD-related pathophysiology compared with sIBM, and open to further research with potential diagnostic and therapeutic implications.

PMID:41520169 | DOI:10.1093/rheumatology/keag016

Oncologist. 2026 Jan 10:oyag003. doi: 10.1093/oncolo/oyag003. Online ahead of print.

ABSTRACT

PATIENTS AND METHODS: we retrospectively collected data of patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i) aiming to describe the patterns of post-progression outcomes.

RESULTS: Among 452 evaluable patients 325 were treated in the first-line setting. Median progression free-survival (mPFS) was 22.8 months overall and 29.7 months in patients treated in first-line setting. Factors associated with outcomes in multivariate analysis were the line of CDK4/6i therapy, de novo vs recurrent disease, visceral vs bone-only metastases, and primary endocrine resistance.A total of 300 patients progressed and 250 overall and 156 in the first-line cohort received a subsequent treatment. Visceral progression and CDK4/6i duration <12 months were associated with a higher likelihood of receiving anthracycline or taxanes (AT) as compared to ET ±everolimus (EET). Post-progression PFS (PPFS) and post-progression OS (PPOS) were statistically significantly better with EET and capecitabine (C) arms over AT overall and in patients with visceral progression. Multivariate analysis confirmed a significant advantage for EET and C, while visceral progression retained a significant impact only on PPOS. After progression to the 1st post-CDK4/6i treatment C obtained a significant better PPOS as compared to other treatments.

CONCLUSION: we showed in a large real-world series that most patients with HR+/HER2- ABC failing CDK4/6i and ET unselected for the occurrence of molecular mutations retain endocrine sensitivity and may benefit of a subsequent ET ± a targeted therapy delaying the need for chemotherapy regardless of site of progression and prior CDK4/6i therapy duration.

PMID:41520162 | DOI:10.1093/oncolo/oyag003