Science Progress最新文献

ObjectiveThis study develops a predictive model to help fire departments improve resource allocation by estimating the likelihood of fire escalation.MethodsWe analyzed 47,382 fire incidents from a city in Taiwan, applying an XGBoost model trained on building characteristics, temporal factors, and geographic information system-derived spatial features. The model was validated using 5-fold cross-validation, temporal holdouts, and geographic tests.ResultsThe model achieved 85.6% accuracy and an AUC of 0.83. Fires were more likely to escalate in older buildings, at night, and on weekends, with building structure, use, and number of floors identified as the strongest predictors. A retrospective simulation suggested that model-informed dispatch could reduce property damage by 25%, firefighter injuries by 21%, and response times by 18%.ImplicationsThese findings demonstrate the potential of predictive analytics to enhance real-time firefighting efficiency and public safety. While promising, the framework requires validation in other cities and with more granular severity scales to ensure broader applicability.

BackgroundDirect oral anticoagulants (DOACs) are first-line medications for stroke prevention in non-valvular atrial fibrillation (AF). However, variability in drug response poses risks of hemorrhagic or thromboembolic events.ObjectivesAlthough genetic influences on DOACs safety are increasingly recognized, robust evidence directly linking specific polymorphisms to bleeding risk remains limited.DesignMulti-center observational case-control study including exome-wide association analysis of 196 non-valvular AF patients treated with rivaroxaban or apixaban, comprising 97 with bleeding complications and 99 without.MethodsDOAC plasma concentrations, urinary 6-β-hydroxycortisol and cortisol levels were measured for CYP3A4 phenotyping. Sequencing was performed on the DNBSEQ G-400 platform. Single-nucleotide variant (SNV) associations with bleeding risk were assessed using logistic regression with additive, dominant, and recessive genetic models. Polygenic risk scores (PRSs) were calculated to evaluate cumulative genetic effects.ResultsNo SNVs reached Bonferroni-corrected significance under any model. PRSs showed weak predictive ability for bleeding with apixaban. For rivaroxaban, regression indicated that ln C_{ss min}/D + 1 index increased with PRS, age, and 6-β-hydroxycortisol/cortisol ratio, but decreased with higher 6-β-hydroxycortisol and coronary heart disease presence. No statistically significant differences were found for the PharmGKB Level 3 variants rs1045642 (rivaroxaban) and rs2231142 (apixaban). Trends toward statistical significance were observed for the rs2472304-G variant in rivaroxaban users, rs6977165-C in apixaban users, and for the CYP3A4*1/*36 diplotype.ConclusionResidual equilibrium concentration of DOACs, including dose-adjusted, did not independently predict bleeding risk in non-valvular AF patients. Variants rs2472304 and rs6977165 may warrant further investigation as potential contributors to bleeding risk.

ObjectiveInflammatory markers, such as the neutrophil-to-lymphocyte Ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and panimmune-inflammatory value (PIV), have previously been identified as prognostic factors in head and neck cancer (HNC). Notably, time-dependent receiver operating characteristic (ROC) curves have rarely been used to assess the prognostic role of inflammatory markers in head and neck cancer. This study aimed to evaluate the significance of the NLR, SII, SIRI, and PIV in this context.MethodsThis retrospective cohort study was conducted at Far Eastern Memorial Hospital, a tertiary medical center between July 2022 and January 2025, and 153 patients with HNC were enrolled in this study. Inflammatory markers were compared by tumor status, nodal involvement, and stage. Time-dependent ROC analysis was used to determine the area under the curve (AUC) and optimal cutoff values for overall survival (OS) and disease-specific survival (DSS) with Cox regression.ResultsThe NLR, SII, SIRI, and PIV were significantly associated with tumor status and stage (p < 0.05). The optimal cutoff values were 2.9, 630, 1.6, and 400, with corresponding time-dependent AUCs of 0.73, 0.71, 0.64, and 0.62, with corresponding sensitivities of 81.7%, 81.2%, 55.9%, and 60.8%, and specificities of 64.1%, 54.9%, 68.5%, and 60.4%., respectively. Higher NLR, SII, SIRI, and PIV values were associated with poor OS and DSS.ConclusionsThe NLR, SII, SIRI, and PIV are associated with tumor status and poor survival outcomes (OS and DSS) and may provide additional stratification and risk-based management in patients with HNC.

Objective: Emerging evidence suggests a potential link between cholesterol metabolism and bleeding. We aimed to examine the causal effect of low-density lipoprotein cholesterol (LDL-C) or lipid-lowering drugs on bleeding outcomes. Methods: Two-sample Mendelian randomization (MR) analyses and two types of drug target MR were conducted to evaluate the associations of LDL-C levels with risks for three bleeding outcomes including intracerebral hemorrhage (ICH), gastrointestinal bleeding (GIBleeding), and hemorrhage from respiratory passages (HRP). Furthermore, the association between LDL-C and bleeding outcomes was re-evaluated in a retrospective cohort study involving patients with coronary artery disease (CAD). Results: MR analyses suggest that LDL-C levels are not associated with bleeding outcomes, including ICH, GIbleeding, and HRP. SMR also found no causal relationship between the use of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) and bleeding outcomes (ICH, GIbleeding, and HRP). Alleles at or near the HMGCR gene (mimicking the effect of statins) reducing LDL-C level expression levels are intended to elevate the risk of ICH (odds ratio (OR) 1.0018, 95% confidence interval (CI) 1.0001-1.0035, P = 0.043), independent of their lipid-lowering effect. In the CAD cohort with a 2-year follow up, LDL-C levels measured within the last 3 months of follow up were significantly associated with an increased risk of BARC criteria 3 to 5 grade bleeding (P < 0.001) and showed a trend toward an increased risk of ICH (P = 0.051). Conclusions: These findings suggest a potential causal relationship between LDL-C levels and bleeding outcomes, particularly in patients using HMGCR inhibitors.

This work utilized Casuarina equisetifolia fruit-based activated carbon (CEAC) to investigate the simultaneous removal of paracetamol (PA), caffeine (CAF), and acetylsalicylic acid (AS) from aqueous solutions. The efficacy of adsorbent removal was investigated using adsorption factors such as pH, CEAC amount, initial pharmaceutical concentration, and adsorption period. Fourier-transform infrared spectroscopy, scanning electron microscopy, and UV-visible analysis confirmed the simultaneous adsorption of the pharmaceutical mixture onto the CEAC surface. The results showed a slight effect of pH on the simultaneous adsorption efficiencies with a CEAC dose of 110 mg. The ideal initial concentration for the pharmaceutical mixture was determined to be 15 mg L^-1. The perfect contact duration for the simultaneous removal of the three pharmaceuticals was found to be 30 min. Kinetic tests demonstrated that the pharmaceutical mixture adsorbs using a pseudo-second-order process. The Freundlich isotherm model describes the equilibrium data. The maximum adsorption capabilities were PA (84.15.23 mg g^-1), CAF (79.16 mg g^-1), and AS (61.32 mg g^-1). A thermodynamic study reveals that these adsorption processes are endothermic and spontaneous. Finally, regeneration experiments confirm the reusability of CEAC.

ObjectiveThe study investigated the role of the quorum sensing (QS) regulator BpsR4 in the physiology and virulence of Burkholderia pseudomallei strain K96243.MethodsA B. pseudomallei bpsR4 knockout mutant (ΔbpsR4) was constructed, and its gene expression profile was compared with that of the wild-type (WT) K96243 strain using RNA sequencing. In vitro assays were conducted to assess growth rates, stress responses, antibiotic sensitivity, motility, and biofilm formation. Ex vivo pathogenicity was evaluated using a human skin fibroblast infection model, and in vivo virulence was assessed in the Galleria mellonella model.ResultsbpsR4 deletion led to significant transcriptional reprogramming, including the downregulation of genes involved in iron acquisition, sulfur metabolism, oxidative stress response, and redox homeostasis and upregulation of genes linked to motility, chemotaxis, and membrane transport. ΔbpsR4 exhibited reduced tolerance to oxidative and heat stress and impaired biofilm formation but no significant change in motility. Additionally, ΔbpsR4 displayed decreased susceptibility to meropenem. In both in vitro and invertebrate infection models, the mutant demonstrated lower virulence than the WT strain.ConclusionThis study highlighted the involvement of BpsR4 in stress response, antimicrobial susceptibility, and virulence in B. pseudomallei. Targeting QS pathways, particularly BpsR4 signaling, might represent a promising strategy to develop anti-virulence therapies that enhance antibiotic efficacy and improve clinical outcomes in melioidosis.

ObjectiveCriteria to differentiate pediatric knee joint effusion remained inexpedient. This study aimed to establish a prediction rule to distinguish infection from other inflammatory arthritis in children presenting with knee pain.MethodsAn ambi-directional cohort was conducted at the university hospital from 1999 to 2021 by including children aged ≤ 15 years with knee pain/swelling, complete physical examination, knee imaging, laboratory, and/or synovial fluid analysis. Contaminated synovial fluid culture and incomplete medical records were excluded. Diagnosis of septic knee (positive joint fluid culture or synovial white blood cell counts > 50,000 cells/mm³) or other inflammatory joints were retrieved. Baseline characteristics, physical examination, and laboratory investigations were analyzed. The probability of septic arthritis was calculated based on numbers of predictors from the final model.ResultsFrom 48 patients (average age 7.0 ± 4.0 years, and 24 (50%) unilateral involvement), the incidence of septic knee was 9 patients (18.8%), and 39 patients with other inflammatory arthritis. Multivariate logistic regression identified three predictors: unable to bear weight, ballottement, and erythrocyte sedimentation rate (ESR) ≥ 75 mm/h (adjusted odds ratio (OR) 36.2, 19.4, and 31.9, respectively, the model chi-square p < 0.0001, with area under receiver operating characteristic curve = 0.9188). Estimated probability of having septic knee according to 1, 2, and 3 predictors was 27.3% (95% confidence interval (CI) 13.3-45.5%), 61.5% (95% CI 31.6-86.1%), and 100% (95% CI 15.8-100%), respectively. The optimal cutoff value from sum of estimated ORs was ≥ 51.29 (at least 2 predictors) with sensitivity 88.89%, specificity 87.18%.ConclusionsThe clinical predictive factors of septic knee in children may be practically determined by unable to bear weight, ballottement, and ESR at least 75 mm/h. The probability of septic knee increases, especially for positive 2-3 factors. Further large studies would benefit for external validating this prediction rule.

To address the critical challenge of thermo-mechanical stress in large-area thin-film transistor fan-out panel-level packaging (TFT-FOPLP), this study employs a finite-element modeling to investigate stress distribution from the panel to the device scale. A hierarchical sub-modeling methodology was used, starting with a homogenized global model to identify high-stress regions, followed by two levels of sub-models to resolve stresses in a single TFT cell under simulated thermal cool-down from fabrication temperatures. Results identified the highest stress concentrations at the corners of dies near the panel edge. At the device level, the analysis revealed that the critical gate insulator is subjected to a tensile stress of approximately 44.5 MPa and a strain of about 0.1%, a level sufficient to potentially alter electrical performance. Furthermore, other brittle dielectric layers, such as the passivation layer, were predicted to experience significantly higher stresses (approximately 407 MPa), indicating a primary risk of mechanical fracture. The study affirms the mechanical feasibility of the TFT-FOPLP concept but underscores the need for careful stress mitigation in vulnerable regions. The presented modeling framework provides a powerful tool for design-for-reliability by enabling the early prediction of high-stress zones, thereby reducing reliance on physical prototyping. Future work should focus on correlating these simulations with experimental electrical data to establish quantitative design rules for this promising technology.

In recent years, the application of aspirin for coronary artery disease has become increasingly common, and aspirin-related enteropathy has gradually garnered more attention. It has increasingly been recognized that the related enteropathy after the long-term use of NSAIDs may have potentially fatal side effects. However, it remains controversial how to select alternative medications for these patients with coronary heart disease, particularly for those who have recently undergone stent implantation. Our case presented with recurrent chest pain and coronary angiography revealed he had severe stenosis in the left anterior descending artery, nearly 90% at the opening, 80% at the middle segments, and a total occlusion at the distal segment, accompanied by a TIMI blood flow grade of 2. However, after five years of taking aspirin, the patient often felt fatigued and was found have megaloblastic anemia and thrombocytopenia. We attempted to prescribe indobufen as an alternative to aspirin for antiplatelet therapy. Fortunately, after several months of follow-up, the patient's symptoms were alleviated, and his hemoglobin and platelet levels returned to normal. Indobufen might be a potential alternative medication for these patients in clinical practice in the future.

ObjectiveMarine organisms such as sea cucumbers represent valuable sources of specialized metabolites with promising applications, making them relevant targets for exploring metabolite distribution and subsequent in-depth characterization. This study aimed to chemically and biologically characterize the parent methanolic extract and its derived fractions, obtained through sequential liquid-liquid partitioning, from the sea cucumber Isostichopus sp. aff. badionotus collected from the Colombian Caribbean Sea.MethodsThe extract and fractions were analyzed using ultra-high-performance liquid chromatography coupled with mass spectrometry and the Global Natural Products Social-based molecular networking platform, enabling dereplication and identification of metabolites. Additionally, the extract and fractions were evaluated against eight Gram-positive and Gram-negative bacterial strains using broth microdilution assays.ResultsThe dichloromethane fractions exhibited the highest antibacterial activity against both Gram-positive and Gram-negative bacteria. For the first time, chemical characterization allowed the identification of a series of metabolites present in the extract and fractions.ConclusionThis study provides the first report on antibacterial activity in I. sp. aff. badionotus, demonstrating that medium-polarity compounds in the dichloromethane fraction exhibited moderate bacterial inhibition, particularly against Gram-positive strains.