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Comorbidity severity adjusted model for predicting mortality in hospitalized patients with COPD
Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, ranking eighth in disability-adjusted life years (DALYs). Patients with COPD frequently exhibit multimorbidity—including cardiovascular disease, cerebrovascular disease, diabetes, and lung cancer. Accordingly, the Charlson Comorbidity Index (CCI) is widely used as a standard tool for comorbidity adjustment; however, as a general-purpose index, it may not fully capture disease-specific patterns of multimorbidity, underscoring the urgency for tailored approaches. Therefore, we aimed to construct a comorbidity severity adjustment model to improve the prediction of in-hospital mortality among COPD patients using large-scale registry data from the Korea Disease Control and Prevention Agency. Method This retrospective study used the Korea National Hospital Discharge In-Depth Injury Survey (KNHDIS) from 2011 to 2023, including 13,385 hospitalized COPD patients (ICD-10 code J44). All analyses accounted for the complex sample design with stratification, clustering, and sampling weights. The baseline model used multivariable logistic regression with conventional covariates, whereas the extended model incorporated comorbidity clusters derived from Apriori association rule mining to capture interconnected disease patterns. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to assess determinants of in-hospital mortality. Result In the baseline model, advanced age, emergency admission, larger hospital size, and higher CCI scores were significantly associated with increased mortality. In the extended model with Apriori-derived clusters, additional high-risk profiles were identified: (i) septicemia with pneumonia, (ii) respiratory failure with sequelae of tuberculosis, and (iii) pulmonary heart disease with sequelae of tuberculosis. The predictive performance improved with the inclusion of comorbidity clusters (AUC 0.753 vs. 0.732), indicating that the cluster-augmented model provided superior discrimination compared with the baseline model. Conclusion These findings indicate that integrating data-driven comorbidity patterns into traditional risk models enhances mortality risk stratification for COPD inpatients and may support both clinical decision-making and the development of evidence-based health policies.
Effect of route familiarity on attentional resource allocation during real-world road driving
Position-dependent feedback drives scaling and robustness of morphogen gradients
Developmental patterning is remarkably robust to intrinsic and extrinsic variation. Morphogen gradients are a key mechanism driving patterning, and themselves often scale with the size of developing tissues and exhibit robustness to other perturbations. Recent data indicate that expander molecules, thought to drive morphogen scaling through expansion-repression (ER) feedback, have concentration profiles that are position dependent. This challenges the currently accepted ER mechanism that requires uniform expander concentrations and position independent feedback. To reconcile these observations, we introduce an ER motif that supports morphogen scaling with both uniform and position-dependent expander concentrations. We quantify scaling as a function of position, and demonstrate that the spatial profiles of scaling and robustness to perturbations in morphogen production are highly correlated. In contrast to uniform expander concentrations that can confer high levels of scaling and robustness at a single position, position-dependent expander concentrations can enhance both scaling and robustness throughout the entire target tissue. We explore trade-offs associated with the dynamic range of the expander concentration, revealing that it can be varied to tune the locations where morphogen gradients confer scaling, robustness, and precision simultaneously. These findings offer insight into how developmental systems balance competing demands to achieve reproducible patterning despite biological variability.
Association between asymptomatic hyperuricemia and kidney stones
Background Nephrolithiasis is commonly observed in patients with gout; however, the role of asymptomatic hyperuricemia in stone formation remains unclear. This study evaluated the association between serum uric acid levels and nephrolithiasis in a large health screening population. Methods We conducted a cross-sectional analysis of 31,198 Korean adults who underwent health checkups between 2010 and 2020. Clinical parameters included anthropometric measures, blood pressure, serum uric acid, renal and hepatic function markers, lipid profiles, glycemic indices, inflammatory biomarkers, serum calcium, and vitamin D3 levels. Nephrolithiasis was defined as the presence of at least one renal stone ≥5 mm detected by ultrasonography and/or kidney–ureter–bladder radiography. Hierarchical logistic regression models (unadjusted, age- and BMI-adjusted, and fully adjusted) were used to assess associations separately in men and women. Results Median serum uric acid concentrations were 6.0 mg/dL in men and 4.4 mg/dL in women. In men, higher serum uric acid levels were associated with nephrolithiasis across hierarchical models. In fully adjusted analyses, serum uric acid remained significantly associated with stone prevalence, and men in the highest uric acid quartile (≥6.9 mg/dL) had higher odds compared with those in the lowest quartile (adjusted OR: 3.546; 95% CI: 1.240–10.144). No statistically significant association was observed in women. Conclusions Higher serum uric acid levels were associated with nephrolithiasis in men but not in women in this cross-sectional analysis. These findings contribute to the epidemiologic understanding of sex-specific differences in stone risk; prospective studies are needed to clarify causality and potential clinical implications.
An examination of the complex climate risks and management approaches confronting the Northeast Tiger and Leopard National Park in the future
Abstract The Northeast Tiger and Leopard National Park is crucial for global biodiversity protection; yet, its environment is under considerable threat from climate change. The absence of a comprehensive grasp of future risk parameters by area managers may impede the development of effective adaptation solutions. This study utilized a “contrasting futures” climatic concept to tackle the issue of “decision uncertainty”. A hybrid statistical downscaling method was employed to downscale CMIP6 multi-model data to 0.1°, selecting two extreme scenarios under the SSP5-8.5 framework: “dry-hot” (EC-Earth3-Veg) and “warm-wet” (MIROC6). The research evaluated two bias correction techniques, quantile mapping (QDM) and random forest (RF), selecting the superior method to produce a high-confidence dataset for the analysis of extreme occurrences. The forecasts indicate that the park will undergo warming in both scenarios, yet the nature and dimensions of the threats vary: the “dry-hot” scenario suggests a substantial rise in temperature, with drought leading to habitat degradation and heightened wildfire risks; the “warm-wet” scenario intensifies ecological corridor disruption and geological disasters resulting from extreme precipitation. The analysis indicates that the regional effects of global climate change impacting the park present a twin threat of compounded drought and flood. The findings offer essential direction for enduring adaptive management and policy structures, highlighting the ineffectiveness of singular catastrophe response approaches and promoting versatile tactics that accommodate several scenarios to safeguard this prominent region.
Attention problems and cortical maturation in a large longitudinal sample of youths: The importance of accounting for sex differences
Delayed age-related cortical thinning has been proposed as a biomarker of attention-related psychopathology and attention-deficit/hyperactivity disorder (ADHD), but these findings have not been adequately replicated in large, longitudinal samples with sufficient power to account for potential confounds such as co-occurring psychopathology and sex differences in neurodevelopment. Here, we examined whether previously reported associations between attention problems and delayed cortical thickness development could be replicated in a large, longitudinal cohort of youths. Leveraging data from the Adolescent Brain Cognitive Development Study, linear mixed-effects models were used to assess the association between parent-reported attention problems (AP) on the Child Behavior Checklist and age-related cortical thickness change (N = 26,496 MRI scans from 11,025 unique participants). Secondary analyses examined the association between a polygenic risk score for ADHD and cortical thickness development. In initial sex-pooled analyses, we observed associations between AP and reduced rates of cortical thinning (β = 00594 to 0.0145, FDR-adjusted P < 0.05). However, when an age × sex interaction term was included in the model, these associations were no longer evident (all FDR-adjusted P > 0.05 across ROIs). Follow-up sex-stratified analyses revealed no significant age × AP interactions on cortical thickness in males or females. Further, there was no evidence of genetic liability for ADHD being associated with reduced age-related cortical thinning. Taken together, these findings suggest that previously reported associations between AP and delayed cortical thinning likely reflect unaccounted-for sex differences in neurodevelopment rather than AP-specific maturational delays, questioning the utility of cortical maturation patterns as diagnostic biomarkers for ADHD-related behavior.
Subsequent memory effect in the inferior frontal gyrus revealed by fNIRS
A central finding in memory research is the subsequent memory effect, which describes consistent neural differences during encoding, where later remembered events elicit higher brain activity than those that are later forgotten, which has been reliably replicated with both EEG and fMRI for the past decades. Replicating the subsequent memory effect using fNIRS could enable research opportunities that are difficult to pursue with other methods, including studies with children, patient populations, or experiments in highly naturalistic settings. Therefore, our study investigated whether the prefrontal cortex is differentially involved in subsequently remembered versus subsequently forgotten stimuli using fNIRS. Our results showed that in particular channels mapping onto the inferior frontal gyrus showed more activation during encoding of subsequently remembered events compared to subsequently forgotten events. These results demonstrate that fNIRS can reliably capture the subsequent memory effect, providing new opportunities to study memory mechanisms across diverse populations and real-world contexts.
Emergence of human enteric adenovirus F41 among children with gastroenteritis in North-central Bangladesh, 2022–2024
Reply to Zadegan et al.: Spatial dependence is real, but not every correction travels well
Fluence to dose equivalent conversion coefficients for ICRP110 voxel phantoms with aluminum and polyethylene shielding using GEANT4
Semantic architectures for domain-specific programming AI agents: lessons from a JavaScript semantic assistant
CD80 (B7-1) as a potential therapeutic target in Epstein–Barr virus‑associated B cell diseases
Abstract Epstein-Barr virus (EBV)-associated B-cell lymphomas pose a therapeutic challenge due to their resistance to conventional chemotherapy and limited efficacy of current targeted approaches. Here, we identified CD80 as a cell surface antigen highly expressed in EBV-positive B-cell lymphomas. Monoclonal antibodies were generated from mice immunized with recombinant human CD80 and subsequently engineered into chimeric formats. These antibodies were evaluated for their cytotoxic activity against CD80-expressing lymphoma cells. Notably, high-affinity clones elicited robust antibody-dependent cellular cytotoxicity (ADCC) but lacked complement-dependent cytotoxicity (CDC), in contrast to rituximab, which targets CD20 and mediates both ADCC and CDC. Our findings suggest that cytotoxic effector functions are regulated not only by the constant region of the antibody but also by the antigen recognized by its variable region. Importantly, these CD80-specific antibodies do not inhibit T cell responses against EBV-positive immortalized cells, highlighting their potential as promising therapeutic candidates for EBV-positive lymphomas and other CD80-expressing malignancies.
Free energy perturbation-derived identification of natural compounds targeting Mycobacterium tuberculosis thymidylate kinase
Uncertainty quantification-based DMEFNet for reliable modelling of heart sound signals
YK-4–250 mitigates gastrointestinal radiation syndrome and promotes overall survival following partial body radiation injury
Thymoquinone protects against statin-induced cerebellar damage, apoptosis, and hepatic cytotoxicity in rats
Abstract Statins are a class of drugs commonly prescribed to lower cholesterol and low-density lipoprotein (LDL) cholesterol levels, as well as to reduce morbidity and mortality associated with cardiovascular illnesses. However, statins are associated with potential side effects, such as muscle pain, liver problems, and neurological or psychiatric disturbances. Therefore, a protective medication is required to mitigate the harmful effects of statins. Thymoquinone (THQ), found in Nigella sativa , has several medicinal benefits and protective effects. The current study aimed to investigate the effects of simvastatin on cerebellar and hepatic tissues, focusing on cellular apoptosis, using light and electron microscopy, morphometric analysis, and immunohistochemical techniques. Additionally, the study evaluates whether thymoquinone can protect against simvastatin-induced histological and ultrastructural damage in hepatic and cerebellar tissues. Thirty adult male Wistar albino rats were divided into three equal groups. Group I was the control group (Ctrl group). Group II (statin group) received simvastatin (20 mg/kg/day) orally for 8 weeks. Group III (statin + THQ group) received concomitant treatment with simvastatin (20 mg/kg/day) and thymoquinone (10 mg/kg/day) for 8 weeks. Tissue specimens were taken from the liver and cerebellum of all animal groups and processed for light and electron microscopic examination. An immunohistochemical investigation for caspase-3 was performed. The molecular and granular layer thickness, number of Purkinje cells, central vein diameter, hepatocyte nuclear diameter, and optical density of anti-caspase-3-positive cells were measured in both the cerebellum and the liver in all experimental groups. Results showed that cerebellum from simvastatin-treated animals showed perinuclear halos in cells within the molecular layer. Purkinje cells appeared disorganized, irregularly arranged, shrunken, with irregular outlines, hyperchromatic nuclei, and vacuolated cytoplasm. Moreover, the granular cell layer appeared shrunken with irregular hyperchromatic nuclei. In addition, decreased thickness of both the molecular and granular layers, as well as a reduction in the number and diameter of Purkinje cells, was observed and confirmed by morphometric analysis. Liver tissue showed shrunken hepatocytes, widened blood sinusoids, widened central veins, and inflammatory cell infiltration. Furthermore, strong positive expression of caspase-3 was observed in both the cerebellum and liver. However, all these histological, ultrastructural, and morphometric changes were markedly decreased after the addition of thymoquinone. It can be concluded that simvastatin induces significant degeneration in both the cerebellar cortex and liver tissue, primarily due to increased oxidative stress and reduced antioxidant protection. Thymoquinone exerts protective effects against this oxidative damage in both organs and alleviates degenerative changes, suggesting that it may be recommended for hypercholesterolemic patients on statins.
Effects of asphaltene from residual crude oil on CO₂ foam stability
Resolving uncertainty in satellite-derived shorelines of a reef-lined beach using high spatiotemporal resolution topographic surveys
Mucinase-engineered cell membrane nanovesicles degrade the glycocalyx shield to potentiate antitumor immunity
The tumor glycocalyx forms a protective shield that masks checkpoint proteins and compromises the efficacy of immunotherapies. While the bacterial protease StcE can degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential is hindered by off-target toxicity and high immunogenicity. To overcome these limitations, we developed a biomimetic platform of cell membrane fusion nanovesicles (FNVs) that codisplay StcE and CD47 nanobodies (nCD47) for spatially controlled glycocalyx degradation and enhanced checkpoint blockade. Using the SpyTag/SpyCatcher system, we generated StcE-displaying NVs, which were then fused with nCD47-displaying NVs. The resulting StcE-nCD47-FNVs retained potent mucin-hydrolyzing activity and exhibited well-defined physicochemical properties. By removing the mucin barrier, StcE-nCD47-FNVs significantly enhanced nCD47 binding to CD47 on tumor cells, thereby potentiating antitumor immune responses. More importantly, benefiting from prolonged circulation of FNVs and tumor targeting of nCD47, the StcE-nCD47-FNV platform demonstrated superior tumor accumulation and biosafety compared to free StcE. In murine models of colorectal and breast cancer, StcE-nCD47-FNVs significantly suppressed tumor growth and metastasis by remodeling the tumor microenvironment, as evidenced by increased M1 macrophage polarization and CD8 + T cell infiltration. By integrating glycocalyx engineering with vesicle nanotechnology, StcE-nCD47-FNVs offer a safe, robust, and versatile strategy to breach the tumor glycocalyx for next-generation cancer immunotherapy.