Search Results (1,413)

Acute respiratory distress syndrome (ARDS) is associated with mortality rates up to 46% and remains challenging to diagnose early due to overlapping clinical presentations. We propose a dual-system framework for multimodal ARDS diagnosis that integrates a Mamba-Bi-LSTM primary discrimination system with a TreeSHAP-based verification system whose attribution outputs iteratively refine the primary system’s feature selection gate. The primary system processes heterogeneous clinical inputs—ventilator parameters, blood gas indices, chest imaging, and EEG signals—through a selective state-space Mamba module and bidirectional LSTM layers. The verification system applies TreeSHAP attribution to independently cross-validate primary outputs, provide clinically interpretable evidence, and supply ${\ell }_1$-normalised attribution vectors that directly modulate the Mamba feature selection gate weights during offline refinement. A confidence-and-consistency decision mechanism governs final output, and high-confidence predictions are incorporated as curriculum-filtered signals to iteratively recalibrate both systems through a confidence-gated offline refinement protocol. Evaluated on 3742 held-out patients from MIMIC-IV (internal test) and 2594 patients from the eICU Collaborative Research Database across 208 US hospitals (external validation), the complete system achieves 92.8% accuracy and an F1 score of 0.889 after offline iterative recalibration on the internal test set, with 91.6% accuracy and F1 of 0.871 on external validation, extending early warning time from 5.2 to 9.7 h. The P/F ratio consistently ranks as the top predictive feature in alignment with the Berlin definition. Ablation experiments confirm that EEG integration independently contributes a 2.7 percentage point accuracy gain and a 1.9-h extension of the warning window (McNemar ${\chi }^2=27.0$, $p<0.001$). All performance improvements over single-modality baselines and over existing methods are statistically significant ($p<0.001$, Bonferroni-corrected). End-to-end processing latency of 350 ms per case is compatible with real-time ICU deployment. Full article

Objectives: This study aimed to investigate the longitudinal associations between breakfast consumption, sleep duration and depressive symptoms among adolescents. Methods: The baseline survey (T1) was conducted from November to December 2019 using a multi-stage stratified cluster sampling method among secondary school students in Shanghai, China. The follow-up survey was conducted about one and a half years later (T2). A total of 2502 adolescents were included in the final analysis. Depressive symptoms were evaluated using the Chinese version of the Patient Health Questionnaire-2 (PHQ-2-C). Breakfast consumption frequency and sleep duration in the past week were self-reported. A cross-lagged model was constructed to examine the longitudinal associations between breakfast consumption, sleep duration and depressive symptoms. Results: The results showed that the prevalence of depressive symptoms and insufficient sleep increased from 15.31% and 89.53% at T1 to 18.47% and 92.89% at T2, respectively. The rate of daily breakfast consumption decreased from 81.10% to 76.06%. The cross-lagged model showed that daily breakfast consumption could significantly predict depressive symptoms (β = −0.109, SE = 0.030, p < 0.001) and sleep duration (β = 0.070, SE = 0.028, p = 0.013). Sleep duration could predict depressive symptoms (β = −0.076, SE = 0.022, p < 0.001) and vice versa (β = −0.039, SE = 0.018, p = 0.028). Conclusions: The rate of daily breakfast consumption among adolescents decreased, alongside the prevalence of depressive symptoms and insufficient sleep increased. Daily breakfast consumption predicted depressive symptoms and sleep duration, whereas depressive symptoms and sleep duration may have a bidirectional association. Full article

Background: Obesity has evolved from a morphometric descriptor to a chronic, relapsing, multisystem disease in which low-grade adipose-tissue inflammation, insulin resistance, endothelial dysfunction, and a prothrombotic, pro-tumorigenic milieu coexist. Venous thromboembolism (VTE) and malignancy share this substrate through a well-established bidirectional link: within twelve months of an unprovoked deep vein thrombosis (DVT), 6–15% of patients are diagnosed with occult cancer, a substantial proportion of which are already locally advanced or metastatic at detection. In this context, obesity acts as a dual amplifier of both thrombotic and oncologic risk, making the post-DVT patient with an incidentally diagnosed cancer a paradigmatic candidate for integrated management. Objective: To propose an evidence-based, unifying cardiometabolic and antithrombotic clinical framework that reconciles (i) risk-stratified screening for occult malignancy after unprovoked DVT, (ii) contemporary pharmacotherapy of obesity, and (iii) cancer-associated thrombosis (CAT) management, in the light of evidence published through 2025. Methods: Narrative synthesis based on a structured literature search (PubMed/MEDLINE, Embase, Scopus; 2000–March 2025) of current guidelines (ISTH, ASH, ESC Cardio-Oncology, EASO) and pivotal randomized evidence on GLP-1 and dual GLP-1/GIP receptor agonists (semaglutide, tirzepatide), SGLT2 inhibitors (empagliflozin, dapagliflozin), and direct oral anticoagulants (DOACs), with critical interpretation of recent meta-analytic data on oncologic signals, cardiovascular outcomes, and bleeding safety. Results: Three evidence-based pillars emerge: (1) limited screening complemented by age- and sex-specific testing in patients ≥ 50 years with unprovoked DVT, enhanced by FDG-PET/CT for high-risk phenotypes in which obesity itself degrades the sensitivity of clinical examination and conventional imaging; (2) GLP-1/GIP receptor agonist-based anti-obesity pharmacotherapy, associated in observational cohorts with a 17% relative reduction in overall cancer incidence (HR 0.83; 95% CI 0.76–0.91) and neutral-to-reassuring oncologic signals, but requiring cautious, case-by-case use in patients with active cancer because of the risk of accelerating sarcopenia and cachexia; and (3) apixaban as the preferred DOAC for cancer-associated thrombosis, with a superior efficacy-to-bleeding ratio in network meta-analyses and a reduced-dose extended strategy now validated by the API-CAT trial. Conclusions: Patients with obesity presenting with unprovoked DVT and an incidentally detected cancer embody a cardiometabolic–antithrombotic continuum. A framework integrating structured occult-cancer screening, judicious obesity pharmacotherapy, and apixaban-preferred anticoagulation—coordinated by a multidisciplinary team and illustrated here by a case-based pathway—offers the most rational, evidence-aligned approach. Prospective, dedicated trials in this specific phenotype are urgently warranted. Full article

Industrial metal surface defect detection is essential for visual sensing-based quality inspection, where lightweight models must balance reliable defect perception and efficient deployment under limited computational resources. However, weak textures, blurred boundaries, and small defect scales often reduce the reliability of lightweight detectors, while heavy global modeling modules increase computational cost. This article proposes a lightweight You Only Look Once (YOLO)-based framework, termed Mediation-based Conflict Mitigation YOLO (MCM-YOLO), for industrial metal surface defect detection. Built upon YOLOv11, MCM-YOLO introduces a C3-Res2Lite (C3-R2L) block to enhance fine-grained local representation and an Aggregated Bidirectional Feature Pyramid Network (Agg-BiFPN) to strengthen multiscale feature aggregation. We further observe that directly coupling the enhanced backbone and strengthened neck may degrade performance, which is referred to as Feature Integration Conflict (FIC). To alleviate the potential feature incompatibility associated with FIC, this article introduces a synergistic attention block, termed MCM-SAB, at the critical interface to perform coordinated channel recalibration and spatial refinement. Experiments on NEU-DET and GC-10 show that MCM-YOLO achieves 80.4% and 65.1% mean average precision (mAP) at an intersection-over-union (IoU) threshold of 0.5, respectively, with 6.3 giga floating-point operations (GFLOPs) and 2.70 million parameters. These results indicate that MCM-YOLO provides a competitive accuracy–efficiency tradeoff for industrial visual inspection. Full article

Live-attenuated rotavirus (RV) vaccines are the most effective interventions for preventing RV gastroenteritis (RVGE) in young children. However, the molecular basis of attenuation remains not well understood. Here, we describe a compact but comprehensive strategy to identify RV virulence determinants by combining low-passage bidirectional selection, sequence analysis, and segment-level phenotype testing via a reverse genetics infectious system. Using the virulent murine RV strain EW, virulence was quantified by diarrhea severity/duration and body-weight gain. Serial passaging in cell culture selected an attenuated population, which regained virulence after passaging in suckling mice. Sequence comparison of the virulent and attenuated EW populations revealed only seven amino acid differences. We summarized literature describing attenuation/virulence-associated mutations in various RV group A (RVA) strains and found previous findings identical or similar to four of the seven mutations: NSP4-T45M, VP4-S470L, VP4-T612A, and VP7-T75P. Virulent- and attenuated-type EW variants of VP2, VP4, VP7, and NSP4 were introduced individually, or as NSP4/VP7 or VP4/VP7 pairs, into a simian SA11-L2 backbone using an 11-plasmid reverse genetics system. Phenotyping of rescued viruses consistently linked cell-culture–adapted VP4 to enhanced replication in vitro and reduced virulence in suckling mice. In vivo passaging strongly favored VP4 residue S470 over cell-culture-selected L470. More generally, our findings (i) underscore VP4 and VP7 as key determinants of EW virulence, (ii) provide a practical framework for identifying driver mutations underlying RVA attenuation, and (iii) highlight attenuation-associated substitutions shared across diverse RVAs. Full article

The global transition toward net-zero emissions has led to the restructuring of labor markets and an intensification of the demand for sustainability-competent business graduates. However, higher-education curricula lack an operationalized, job-competency-based framework, and this gap in knowledge is especially acute in emerging industrial economies that are facing pressures due to the ongoing decarbonization of the global supply chain. In this context, this study addresses two interrelated gaps in the relevant research: the lack of a structured system of criteria to assess competency in sustainability that is specifically geared toward business education, and the insufficient attention that has been paid to causal interdependencies among such criteria in previously developed frameworks. The authors apply a two-stage, hybrid multiple-criteria decision-making design based on the KSAO framework, which classifies professional competency into knowledge (K), skills (S), abilities (A), and other characteristics (O). A modified Delphi method that involved 12 academic and industry experts serving as surrogate assessors of competency requirements for business and management students was first used to consolidate 142 literature-derived items into 26 initial criteria, which were then refined into 12 core competencies in sustainability, identified through cross-domain expert consensus. Following this, fuzzy Decision-Making Trial and Evaluation Laboratory (DEMATEL) was applied to analyze the structure of causal influence among the retained criteria. The results identified interdisciplinary work as the primary driving competency and integrated problem-solving as the central hub with the highest prominence, with the two factors forming a bidirectional feedback dynamic that anchored the competency system. The retention of four “other” criteria (O-dimension)—ethical values, normative orientation, empathy, and adaptive resilience—confirmed that competency concerning sustainability in business education extends beyond technical knowledge into deeper dispositional attributes. These findings provide business schools in Taiwan with a structurally grounded logic of sequencing for their curricula, as well as a reference framework for curriculum design that is aligned with the Association to Advance Collegiate Schools of Business (AACSB) Societal Impact standards. While the findings are grounded in Taiwan’s specific ESG regulatory and industrial context, only the methodological approach is offered as a reference for comparable settings; the substantive findings require cross-national verification. Full article

Cow-based calf rearing (dam- or foster cow-based) is gaining popularity as a relatively natural husbandry practice. However, direct udder contact by calves creates a bidirectional transmission route for pathogens. The objective of this cross-sectional study was to investigate the prevalence and concordance of mastitis-associated pathogens in the milk of cows and the saliva of corresponding calves at the time of weaning. On 15 organic dairy farms, milk samples from 269 cows and saliva samples from 403 calves were collected at weaning. Pathogen differentiation was performed via Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF), and strain typing was additionally conducted via randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Dominant pathogens in milk were Non-aureus-Staphylococci (NaS)/Mammaliicoccus spp. and Corynebacterium spp., and in calf saliva, NaS/Mammaliicoccus spp. (primarily M. sciuri, S. xylosus). There were a total of 12 strain concordances, exclusively in foster cow–calf pairs (Fisher’s exact test, p = 0.012). The highest observed/expected ratio was found for P. multocida (21.1). For S. aureus, strain matches were found in 3 foster cow–calf pairs across 2 farms. Direct strain concordance was generally observed rather rarely. The observed strain concordances suggest transmission between cows and calves, particularly for S. aureus and P. multocida. NaS and Mammaliicoccus spp. concordances are likely attributable to a common environmental source. Full article

In unmanned farms, machinery transfer between fields and access to field entrances are essential prerequisites for autonomous field operations, and both require support from an accurately structured farm-road network. However, existing road data are typically maintained as vector layers and lack the topological relationships and geometric attributes needed for transfer-route and field-entrance planning. This study proposes a method for constructing farm-road topological maps from road and field vector data. The method converts road polygons into a node–edge graph containing centerline geometry, estimates road-segment widths to support the safe passage of agricultural machinery, and establishes bidirectional road–field associations based on field-access nodes. Experiments in three farm areas show that the proposed method achieves a mean symmetric centerline error of 0.094 m; width-estimation mean absolute error (MAE) and root mean square error (RMSE) of 0.032 m and 0.060 m, respectively; and a 100% success rate in 50 random path-planning tasks. The farm-road topological map constructed by this method provides spatial infrastructure for agricultural-machinery path planning and operation scheduling in unmanned farms. Full article

Adverse pregnancy outcomes (APOs), including preterm birth, preeclampsia, low birth weight, recurrent miscarriage, gestational diabetes mellitus, and fetal growth restriction, remain major threats to maternal and offspring health. Increasing evidence links the maternal microbiome to pregnancy health, but most studies have examined individual microbial niches rather than their interactions. The oral cavity and gut are anatomically and immunologically connected and form a bidirectional oral–gut microbiota axis through microbial trafficking, immune signaling, and metabolite-mediated feedback. Emerging studies suggested that oral dysbiosis, periodontal inflammation, and gut microbial remodeling were associated with APOs, although direct causal evidence in human pregnancy remains limited. This review summarizes pregnancy-related remodeling of the oral–gut microbiota axis, evaluates clinical and experimental evidence linking oral and gut dysbiosis to APOs, and discusses potential mechanisms, including microbial translocation, immune and inflammatory activation, metabolic remodeling, epigenetic regulation, and outer membrane vesicle-mediated signaling. Candidate biomarkers, probiotic and dietary intervention strategies, and current translational limitations are also discussed. Overall, the oral–gut microbiota axis offers a useful framework for understanding microbiome-associated APOs, but standardized sampling, longitudinal cohorts, and mechanistic validation are required before clinical application. Full article

Growing recognition of the gut–kidney axis has revealed that gut dysbiosis and altered mucosal immunity are intimately intertwined with acute kidney injury (AKI). Gut changes following AKI, including dysbiosis and associated altered metabolites, barrier disruption, and maladaptive immune responses, affect post-AKI outcomes in a bidirectional manner. Therefore, the gut is increasingly recognized as a previously underappreciated modifier of AKI, and recent research is beginning to dissect the causal relationships between microbial perturbations and AKI, as well as the mechanisms underlying these complex interactions. However, relevant data remain limited, underscoring the need for further mechanistic and translational studies to fully elucidate key pathways for the development of novel, gut-targeted therapeutics. In this review, we summarize the mechanisms by which gut dysbiosis contributes to AKI outcomes and discuss gut-based therapeutic options based on experimental and clinical studies as well as future perspectives. Full article

Ventricular tachycardia and sudden cardiac death remain the principal late causes of mortality in repaired tetralogy of Fallot. Clinical practice is evolving from a “reactive” paradigm centered on defibrillator therapy and post-event ablation toward a “proactive” paradigm targeting slowly conducting anatomical isthmuses before clinical arrhythmias become manifest. Monomorphic ventricular tachycardia in this population typically occurs due to a discrete, anatomically defined set of slowly conducting isthmuses bounded by surgical patches or incisions and valve annuli. Substrate-targeted catheter and surgical ablation are technically feasible, safe, and associated with high arrhythmia-free survival when complete bidirectional block is achieved. The current indication for “proactive” ablation is for substrate evaluation before transcatheter pulmonary valve replacement, after which endocardial access to the dominant isthmus may be permanently obscured. Pulmonary valve replacement alone does not abolish the arrhythmogenic substrate, thus providing the rationale for combining valve intervention with proactive ablation. This narrative review discusses substrate biology, risk stratification, comparative outcomes of reactive and proactive ablation strategies, and the role of pulmonary valve replacement. It also proposes an operational pathway integrating both approaches within shared decision-making. The ongoing CATAPULT-TOF study and subsequent multicenter work will determine the populations in which proactive substrate evaluation should become routine. Full article

This article examines the maturation of the Astana Hub technology park and its association with Kazakhstan’s national digital competitiveness during the country’s transition from resource dependency toward a higher value-added digital economy. As Central Asia’s largest international technology park, Astana Hub provides a policy-relevant case of a state-initiated open-innovation ecosystem. To proxy the national enabling environment, we construct the Kazakhstan Digital Performance Index (KDPI), a composite measure that normalizes and aggregates three publicly available global indices: the UN E-Government Development Index (EGDI), the Global Innovation Index (GII, WIPO), and the Network Readiness Index (NRI, Portulans Institute). Using an Interrupted Time Series (ITS) design over 2010–2024, we estimate the change in the level and slope of national IT service exports associated with the establishment of the Hub in 2018. The analysis identifies a statistically significant post-2018 increase in the export-growth slope of approximately $112.8 million per year relative to the pre-intervention trend, alongside a near 20-fold rise in IT service exports between 2020 and 2024. By contrast, the composite KDPI shows no comparable acceleration, and an exploratory correlation analysis over the short post-2018 window indicates a positive association between Hub growth and e-government infrastructure but a negative association with the GII. We interpret these patterns cautiously as descriptive evidence consistent with a temporary “island of efficiency,” in which commercial scaling has outpaced economy-wide innovation diffusion, rather than as confirmation of a bidirectional feedback loop or of causal national-level human-capital effects, which the single-country quasi-experimental design cannot establish. The paper discusses policy options for diffusing Hub capabilities into the wider economy and sets out the limitations of the design. Full article

Introduction: Functional gastrointestinal disorders (FGIDs), conceptualized as disorders of gut–brain interaction, are among the most common chronic or recurrent conditions in childhood, affecting approximately 20–30% of children worldwide across community and clinical settings. FGIDs are associated with substantial impairments in quality of life, frequent school absences, and high levels of psychological comorbidity, contributing to a considerable burden for families and healthcare systems. Despite their high prevalence, the pathophysiology remains incompletely understood, with evidence pointing to a multifactorial interplay of biological, psychological, and environmental factors. Given their frequency across healthcare settings and their significant psychosocial and economic impact, a better characterization of FGIDs in real-world pediatric populations is needed. This retrospective chart review aimed to examine patterns of FGIDs and their associations with gender, temporal factors, geographic setting, and hospitalization burden in a Swiss pediatric cohort within a biopsychosocial framework. Methods: This retrospective chart review study included 1445 patients aged 0–18 years. Patients were selected based on having received an ICD-10 diagnosis attributed to FGID. The frequency and distribution of the aforementioned factors were determined, as well as their associations with each other. Results: A male predominance of FGIDs in newborns (p < 0.001), a female predominance in adolescents (p < 0.001), and sex-based differences in subtype distribution (p < 0.001) was found in this cohort of patients. A higher proportion of FGID cases were found among children in urban areas than in rural and suburban areas. Infants were hospitalized for significantly longer periods on average than older children and males were hospitalized for longer periods on average than females. Discussion and Conclusions: These findings highlight the importance of early, integrated, interdisciplinary care pathways. Given the growing mental health issues affecting adolescent girls and the well-documented bidirectional relationship between emotional stress and FGID symptoms, it is suggested that early psychological screening and family-based interventions could reduce the chronicity of symptoms, prevent unnecessary hospitalizations and improve long-term health outcomes. Full article

Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article

Circulating tumor DNA (ctDNA) was initially conceived as a minimally invasive surrogate for interrogating cancer biology; however, three decades of evidence have demonstrated that plasma is not a passive reservoir of tumor-derived material, but rather a dynamic and biologically heterogeneous milieu in which multiple competing genomic signals coexist. This review explores the level of interpretive rigor required to translate ctDNA detection into clinically actionable precision oncology. Clonal hematopoiesis of indeterminate potential (CHIP) is discussed not as an occasional confounder, but as an intrinsic source of biological background noise, underscoring the critical importance of matched leukocyte sequencing to discriminate tumor-derived alterations from hematopoietic variants, particularly in older individuals and in patients previously exposed to cytotoxic therapies. The widespread assumption that variant allele frequency (VAF) directly reflects tumor burden is critically re-evaluated through the mathematical relationships linking VAF to tumor fraction, local copy-number architecture, and mutation multiplicity. Within this framework, estimation of cancer cell fraction (CCF) and probabilistic discrimination between clonal and subclonal events are examined, including the emergence of reversion mutations as molecular evidence of therapy-driven evolutionary adaptation. The review also addresses the central paradox of ultra-sensitive sequencing technologies: although unique molecular identifiers and duplex sequencing can extend analytical sensitivity below 0.01% VAF, sensitivity in the absence of contextual specificity risks conflating technical artifacts and biologically insignificant alterations with clinically meaningful disease. Equal emphasis is placed on pre-analytical variables, highlighting how sample collection, stabilization, and processing protocols define the upper limit of downstream analytical reliability. Beyond single-nucleotide variants, fragmentomic and methylation-based approaches are presented as complementary orthogonal dimensions capable of revealing tumor-associated signals even when mutational evidence is limited or absent. Longitudinal ctDNA assessment is argued to provide substantially greater biological and clinical insight than isolated static measurements, while robust clinical reporting is shown to depend on transparent disclosure of assay limitations, residual uncertainty related to CHIP, and structured bidirectional communication between molecular laboratories and treating clinicians. Ultimately, the transition from a biomarker-centered model toward an integrated systems-based framework, combining genomics, epigenomics, fragmentomics, and evolutionary modeling, emerges as the defining challenge for the next generation of liquid biopsy in precision oncology. Full article