• Machine Learning and Deep Learning Frameworks for Human-Virus Protein-Protein Interaction Prediction: Emerging Architectures, Methods, Benchmarks, and Challenges.
    3 weeks ago
    The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. Coronaviruses are a diverse group of RNA viruses classified into alpha, beta, gamma, and delta genera, with SARS-CoV-2 belonging to the beta-coronavirus family. The virus exhibits high transmissibility and causes a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to severe complications such as acute respiratory distress syndrome, multi-organ failure, and death, particularly among elderly and immunocompromised individuals. Structurally, SARS-CoV-2 possesses a large single-stranded RNA genome encoding major structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, which play critical roles in host-cell recognition and viral infection. Understanding the molecular mechanisms of virus-host interactions, especially protein-protein interactions (PPIs), is essential for uncovering viral pathogenesis and identifying potential therapeutic targets. Traditional experimental techniques for PPI detection, such as yeast two-hybrid and affinity purification methods, are often expensive, labor-intensive, and prone to inaccuracies. Consequently, computational approaches based on machine learning (ML) and deep learning (DL) have gained significant attention for efficient and scalable PPI prediction. These methods use diverse biological information, including protein sequences, structural features, genomic data, Gene Ontology annotations, and interaction networks, to model complex biological relationships. This survey reviews computational approaches to PPI prediction, highlighting ML- and DL-based techniques, methodological advances, performance evaluation practices, and limitations that affect benchmark comparability. It also discusses biological databases and data sources commonly used in PPI studies and explicitly considers how models trained in coronavirus-centered settings may generalize to other viral families with different mechanisms of host interaction.
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  • SARS-CoV-2 Infection Exacerbates Hypertensive Disorders in Pregnancy Through Vascular and Immune Pathways.
    3 weeks ago
    SARS-CoV-2 infection has been linked to an increased risk of hypertensive disorders during pregnancy, particularly preeclampsia (PE). As both conditions involve vascular and endothelial dysfunction, a mechanistic overlap has been proposed. This study examines the relationship between maternal COVID-19 and preeclampsia by analyzing inflammatory, endothelial, and angiogenic biomarkers in pregnancies with and without these complications.

    A case-control study was conducted, including four groups: healthy pregnancies before 2020 (n = 10), preeclampsia cases before 2020 (n = 10), COVID-19 cases without preeclampsia (n = 10), and COVID-19 cases with preeclampsia (n = 10). The groups were selected to be comparable in terms of gestational age at blood sampling. Biomarkers related to endothelial, inflammatory, and angiogenic pathways were measured.

    Significant differences in biomarker levels were detected among the four groups. Regarding endothelial damage, sICAM1 levels were significantly higher in the COVID-PE group compared with the COVID-noPE group (p = 0.002). Additionally, vWF (p = 0.006), END1 (p < 0.001), and sVCAM1 (p = 0.030) levels varied significantly across groups. IL8 levels showed significant differences (p < 0.001), and were particularly elevated in preeclampsia cases (preCOVID-PE and COVID-PE groups) compared with controls (p = 0.005 and p < 0.001, respectively). Angiogenic markers sFlt-1, PLGF, and sFlt-1/PLGF exhibited significant group differences (p < 0.001). In contrast, maternal SARS-CoV-2 infection in the absence of preeclampsia was not associated with a significant alteration of the sFlt-1/PlGF ratio.

    PE associated with SARS-CoV-2 infection preserved the classical angiogenic signature of preeclampsia, but showed additional endothelial and inflammatory biomarker alterations. These findings support an association between SARS-CoV-2 infection and a distinct endothelial and inflammatory biomarker profile in PE, warranting confirmation in larger prospective studies.
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  • Health literacy-sensitive self-management interventions for chronic obstructive pulmonary disease: a systematic review and meta-analysis.
    3 weeks ago
    Chronic obstructive pulmonary disease (COPD) requires sustained self-management, and health literacy may play an important role in patients' ability to understand, implement, and maintain disease-management behaviors. However, the effectiveness of self-management interventions incorporating health literacy-sensitive components in COPD remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating health literacy-sensitive self-management interventions for adults with COPD. Health literacy-sensitive self-management interventions were defined as self-management programs incorporating explicitly identifiable strategies intended to reduce literacy-related barriers or to support patients in obtaining, understanding, appraising, or applying COPD-related health information in daily self-management. Nine databases were searched from inception to August 30, 2025. Thirty-one randomized controlled trials involving 4759 participants were included. Outcomes included 6 min walk distance (6MWD), forced expiratory volume in 1 s as a percentage of predicted value (FEV₁% predicted), St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT), and self-management-related outcomes. Risk of bias was assessed using the Cochrane Risk of Bias tool, and pooled effects were calculated using fixed- or random-effects models according to heterogeneity. Compared with usual care, self-management interventions with health literacy-sensitive components were associated with improvements in 6MWD (MD = 44.81 m, 95% CI 17.48-72.14; p = 0.001), FEV₁% predicted (MD = 7.43, 95% CI 6.31-8.55; p < 0.00001), SGRQ total score (MD = -6.80, 95% CI -9.80--3.80; p < 0.00001), mMRC score (MD = -0.40, 95% CI -0.61--0.19; p = 0.0002), CAT score (MD = -3.78, 95% CI -5.49--2.07; p < 0.0001), and self-management-related outcomes (SMD = 1.50, 95% CI 1.34-1.67; p < 0.00001). Substantial heterogeneity was observed for several outcomes, particularly 6MWD, SGRQ, mMRC, CAT, and self-management-related outcomes. Health literacy-sensitive self-management interventions were associated with improvements in exercise capacity, pulmonary function, symptom burden, dyspnea, health-related quality of life, and self-management-related outcomes in patients with COPD. However, the evidence should be interpreted with caution because eligible interventions were defined by the presence of explicitly identifiable health literacy-sensitive strategies embedded within self-management programs, rather than by isolated health-literacy enhancement alone, and substantial heterogeneity and variable methodological quality were present across studies. More rigorously designed and standardized trials are needed to clarify the specific contribution of health literacy-sensitive strategies and their long-term effectiveness in COPD care.
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  • Mapping the characteristics of training for vocal conditioning of singers: a scoping review.
    3 weeks ago
    To map and characterize intervention strategies for the vocal conditioning of singers without vocal complaints.

    Scoping review based on the question: How are the intervention strategies used for vocal conditioning of singers characterized? Searches were conducted in the following sources: LILACS, MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, Google Scholar, medRxiv, ProQuest, Journal of Singing, and the Brazilian Digital Library of Theses and Dissertations.

    Studies with vocal or respiratory training of singers without vocal complaints, of any musical genre, over 18 years of age, were included. Studies with children, other voice professionals, participants with laryngeal and vocal alterations, voice rehabilitation, exclusively indirect approach or those that did not focus on vocal conditioning were excluded.

    The results were summarized in tables and charts.

    A total of 12,358 studies were identified, eight of which met the eligibility criteria. The approaches focused on respiratory muscle strength and Semi-occluded Vocal Tract Exercises stood out. The number of repetitions together with monitoring of the total execution time was the most used. The duration of the interventions ranged from three weeks to six months and most of the training programs were conducted by speech-language pathologists and professionals from other areas. There was a predominance of self-assessments, with mostly positive results.

    Variability was found in the intervention strategies used. The focus on simultaneous work between breathing and voice stood out, with respiratory muscle strength and Semi-occluded Vocal Tract exercises being the most used techniques.
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  • Serratia marcescens in Intensive Care Units: Molecular Epidemiology, Biofilm-Mediated Persistence, Antimicrobial Resistance, and Genomic Surveillance.
    3 weeks ago
    Serratia marcescens has emerged as an important opportunistic pathogen in intensive care units (ICUs), where critically ill patients, invasive devices, antimicrobial exposure, and complex environmental reservoirs create favorable conditions for colonization, infection, and recurrent outbreaks. This narrative review synthesizes evidence from the past decade regarding the clinical and molecular epidemiology, environmental persistence, device-associated transmission, biofilm-mediated resistance, and infection-control strategies of S. marcescens in ICU settings. The literature was reviewed using an integrative approach informed by Ferrari's narrative review framework, with thematic synthesis across clinical, microbiological, environmental, and genomic domains. Recent evidence indicates that ICU-associated S. marcescens infections frequently involve respiratory tract colonization, ventilator-associated pneumonia, bloodstream infection, urinary tract infection, and device-related transmission. Hospital water systems, sink drains, wet surfaces, ventilator circuits, reusable equipment, and contaminated antiseptic or liquid products may serve as persistent reservoirs, particularly when biofilm formation supports long-term survival and recurrent dissemination. At the molecular level, S. marcescens demonstrates substantial genomic diversity, intrinsic and acquired antimicrobial resistance, inducible AmpC β-lactamase activity, efflux-mediated tolerance, and plasmid-associated resistance gene transfer. This review particularly emphasizes the molecular determinants that enable S. marcescens to persist in ICU ecosystems, including AmpC-mediated β-lactam resistance, efflux-associated tolerance, quorum-sensing-regulated biofilm formation, plasmid-mediated horizontal gene transfer, and WGS-defined clonal transmission. Whole-genome sequencing, rapid molecular diagnostics, active surveillance, environmental sampling, and integrated infection-control bundles have become increasingly important for distinguishing clonal outbreaks from endemic transmission and guiding timely interventions. Emerging perspectives emphasize the need to combine antimicrobial stewardship, environmental engineering, respiratory-care auditing, anti-biofilm strategies, and AI-assisted real-time surveillance into adaptive ICU infection-control frameworks. Overall, S. marcescens should be regarded not merely as an episodic outbreak organism, but as a highly adaptable ICU-associated pathogen requiring multidisciplinary prevention strategies.
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  • Identification of Inflammasome-Related Genes and Their Role in Predicting Community-Acquired Pneumonia.
    3 weeks ago
    Community-acquired pneumonia (CAP) is a common respiratory infectious disease worldwide, posing a significant threat to human health. In recent years, the crucial role of inflammasomes in the occurrence and development of pneumonia has gradually been recognized. This study aims to systematically explore potential diagnostic biomarkers related to inflammasomes in CAP. CAP transcriptome datasets GSE103119 and GSE196399 were obtained from the GEO database. First, we conducted differential expression analysis and combined it with weighted gene co-expression network analysis to screen inflammasome-related differentially expressed genes (DEIRGs). Subsequently, we carried out Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis. Then, based on multiple machine learning algorithms [least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE), Boruta, and random forest], we performed feature gene selection and combined a support vector machine (SVM) to construct a classification model. The diagnostic performance was evaluated in the training set and validation set through the receiver operating characteristic curve and precision-recall curve. Finally, we collected peripheral blood samples from 5 patients with CAP and 5 healthy controls and used quantitative real-time polymerase chain reaction (qRT-PCR) to verify the expression differences of candidate genes. A total of 414 DEIRGs were identified, mainly enriched in immune response regulation, Th17 cell differentiation, and autophagy pathways. Combined with machine learning and SVM analysis, the LASSO and RFE models showed the best performance in CAP diagnosis. Based on the intersection of these two algorithms, RPL39, INSL3, and vimentin (VIM) were ultimately determined as the core candidate genes. The qRT-PCR results further confirmed that in CAP peripheral blood samples, INSL3 and VIM showed significantly increased expression, while RPL39 showed decreased expression, which was consistent with the bioinformatics prediction. This study identifies RPL39, INSL3, and VIM as potential diagnostic markers for CAP, which may provide new evidence for early diagnosis and stratified management.
    Chronic respiratory disease
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  • Associations Between Welding-Related Metals and Atherosclerotic Cardiovascular Disease Risk in Male Welders: The Mediating Role of Accelerated Biological Aging.
    3 weeks ago
    The impact of metals on atherosclerotic cardiovascular disease (ASCVD) risk in workers occupationally exposed to welding fume remains unclear. We aimed to assess the associations between welding-related metals and 10-year ASCVD risk, and the mediating role of biological aging. Metals including chromium, manganese, nickel, lead, copper (Cu), and iron were detected and biological aging indices, including Klemera-Doubal method biological age (KDM-BA) and Phenotypic Age (PhenoAge), were calculated among 419 male welders in Wuhan, China. The participants had an average age of 42.77 years, of whom 93 (22.2%) fell into the high 10-year ASCVD risk group. Generalized linear models revealed that Cu was associated with elevated 10-year ASCVD risk [OR (95% CI) = 1.051 (1.017, 1.085), P = 0.003]. This association persisted even after adjustment for other metals. Moreover, we found positive associations between biological aging and 10-year ASCVD risk [KDM.Accel: OR (95%CI) = 1.170 (1.070-1.280); PhenoAge.Accel: OR (95% CI) = 1.122 (1.053-1.194)], as well as between Cu and biological aging [KDM.Accel: β (95% CI) = 1.888 (1.130-2.646); PhenoAge.Accel: β (95% CI) = 4.552 (3.406-5.698)]. Further analysis showed significant mediation roles of KDM.Accel and PhenoAge.Accel in the Cu-ASCVD association, with mediating proportions of 29.8% and 43.8%, respectively. We further constructed a lifestyle index, suggesting that a modifiable healthy lifestyle could decelerate aging and reduce the 10-year ASCVD risk. Our findings indicated that Cu was associated with increased ASCVD risk, and biological aging may mediate the Cu-ASCVD association. Adopting healthy lifestyles appears to mitigate biological aging, which is of great public health importance for preventing ASCVD.
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  • Epigenetic Control of Mammalian Cardiomyocyte Proliferation.
    3 weeks ago
    Postnatal shutdown of the mammalian cardiomyocyte cell cycle underpins limited regenerative capacity of the adult heart. An epigenetic programme regulates a switch at birth from a proliferative state to functional maturity. Identification of the molecular components regulating this switch has revealed therapeutic opportunities for heart regeneration that have started entering the clinic.

    Genome-wide analyses reveal that histone modifications and DNA methylation remodel chromatin in adult cardiomyocytes, downregulating cell cycle activation genes while upregulating maturation genes. Epigenetic regulation of upstream transcriptional pathways (e.g. YAP, WNT and Notch) prevents cell cycle activation in the adult heart. Upregulating glycolysis or suppressing oxidative metabolism enhances cardiac repair following injury, with hypoxia demonstrating safety in humans. Gene therapy techniques enabling myocardial targeting have enhanced the translation of cardiac regenerative therapies, with YAP upregulation paving the way for future trials. The cardiomyocyte cell cycle is regulated by CDKs/cyclins controlled by transcriptional networks that are epigenetically suppressed in the postnatal period. Adult cardiomyocytes also harbour structural barriers and a metabolic state preventing proliferation. Pharmacological and genetic manipulation of these mechanisms can re-activate adult cardiomyocyte proliferation. However, regenerative therapies are challenged by the intrinsic link between proliferation and epigenetics, metabolism, and ultimately cardiac function.
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  • Determinants, risk score, and prognostic implications of left ventricular thrombus in ischemic cardiomyopathy assessed by cardiac magnetic resonance: a retrospective cohort study.
    3 weeks ago
    Left ventricular thrombus (LVT) is a significant complication in ischemic cardiomyopathy (ICM). However, factors associated with LVT have mainly been reported in patients with recent myocardial infarction (MI), while data in chronic ICM remain limited. This study aimed to identify factors associated with CMR-detected LVT in patients with chronic ICM (left ventricular ejection fraction [LVEF] < 50% of ischemic etiology, >40 days post-MI), develop a CMR-based risk score, and evaluate the prognostic implications of LVT on major adverse cardiovascular events (MACE).

    This study included 790 patients with ICM who underwent CMR at an academic hospital in Thailand between 2016 and 2023. Factors associated with LVT were identified using logistic regression analyses. A CMR-based risk score was developed and validated, with discriminative performance assessed by the area under the receiver operating characteristic curve (AUC-ROC). MACE, defined as a composite of cardiovascular death, ischemic stroke, transient ischemic attack, systemic embolism, nonfatal MI, or heart failure hospitalization, was also evaluated. Factors associated with MACE were assessed using Cox regression analysis.

    The mean age was 66.9 ± 11.3 years, and 75.3% were male. LVT was detected in 116 patients. Independent factors associated with LVT included apical aneurysm, apical late gadolinium enhancement (LGE), and the number of LGE segments. The CMR-LVT Score, incorporating these variables, demonstrated an AUC of 0.73 (95%CI, 0.68-0.77;p < 0.001) in the derivation cohort and 0.79 (95%CI, 0.69-0.90;p < 0.001) in the validation cohort. During a median follow-up of 3.2 years (IQR, 1.6-5.5), 150 MACE occurred. Baseline LVT was independently associated with MACE (adjusted HR 2.38, 95%CI 1.31-4.30;p = 0.004).

    In patients with ICM undergoing CMR, apical aneurysm, apical LGE, and LGE extent were independently associated with LVT. The CMR-LVT Score demonstrated acceptable discriminative performance for identifying higher-risk patients who may benefit from more intensive follow-up. LVT was also independently associated with MACE.
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  • A practical approach to Cardiopulmonary Exercise Testing: from functional evaluation to adapted exercise prescription.
    3 weeks ago
    This expert opinion paper focuses on the clinical implementation, execution and interpretation of Cardiopulmonary Exercise Testing (CPET), providing comprehensive insights into its recognised prognostic, diagnostic and prescriptive value in everyday clinical practice. A practical guide offers step-by-step instructions on conducting and interpreting CPET, emphasising the importance of high-quality testing for the benefit of patients, healthy individuals and athletes. The approach considers test objectives, how to adapt procedures for different medical inquiries and reporting. A systematic method for interpreting CPET data is outlined, covering aerobic/exercise capacity evaluations with subsequent analyses of ventilatory, cardiovascular, cardiorespiratory gas-exchange and muscular-metabolic responses to exercise. Special attention is given to post-exercise recovery and other novel parameters for informed clinical decision-making. The outcomes emphasise the need for better implementation of CPET for prognostic evaluations and in diagnostic pathways. Barriers to its adoption are discussed, including logistical challenges or resource constraints, and strategies for integrating CPET into routine care pathways are proposed. The statement provides further details on how to utilise CPET outcomes to tailor exercise prescription based on identified functional limitations and adjust exercise intensity using different physiological and pathological thresholds for both patients and athletes. Finally, the latest advancements in CPET are explored, including novel portable systems and integration with transcutaneous blood-gas monitoring, imaging, and (non-)invasive haemodynamic measures, also addressing the potential for smaller clinics, improving accessibility in clinical practice. This expert opinion statement aims to offer a roadmap for making CPET a more standardised and accessible tool in clinical care.
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