Browse Articles

Computation embodied in population geometry

Understanding pedestrian crash patterns using bayesian probabilistic structural equation modeling

Native yeast kinetochore structures identify an essential inner kinetochore interaction

Abstract Kinetochores must accurately assemble on centromeres for faithful chromosome segregation. Although a conserved centromeric nucleosome is essential for kinetochore assembly, budding yeast centromeric DNA is a poor template for nucleosome formation in vitro, perhaps due to its intrinsic rigidity. To better understand yeast inner kinetochore assembly, we develop a one-step protocol to purify native inner kinetochore subcomplexes for structural studies. We perform cryoelectron microscopy on the purifications and generate density maps of four separate inner kinetochore complexes, two of which have not been previously visualized and may represent intermediate assemblage states. We identify an Ndc10 trimerization domain that engages centromeric DNA and a pair of CBF3 complexes and is associated with substantial bending of centromeric DNA. Ndc10 trimerization is essential for kinetochore assembly and chromosome segregation. We propose that Ndc10 trimerization facilitates centromeric DNA bending to stabilize the centromeric nucleosome and inner kinetochore.

A randomized noninferiority trial comparing tegoprazan triple therapy and bismuth quadruple therapy for Helicobacter pylori eradication

Abstract Rising antibiotic resistance has compromised the efficacy of standard Helicobacter pylori ( H. pylori ) eradication regimens. This multicenter trial aimed to evaluate whether a simplified tegoprazan-based triple therapy (TAD) is non-inferior to tegoprazan-based bismuth quadruple therapy (TADB) in a high-resistance setting. In this randomized, open-label, non-inferiority trial conducted across nine centers in China, 274 treatment-naïve patients were randomized (1:1) to receive either Group TAD (tegoprazan 50 mg, amoxicillin 1000 mg, doxycycline 100 mg) or Group TADB (TAD plus bismuth potassium citrate 600 mg) twice daily for 14 days. In the per-protocol (PP) analysis, eradication rates were 91.7% (111/121) for Group TAD and 96.0% (120/125) for Group TADB. Using the Newcombe score method against a pre-specified non-inferiority margin of -10%, the difference in per-protocol eradication rates was − 4.3% (95% CI: -9.8% to 2.0%), successfully establishing statistical non-inferiority. Intention-to-treat (ITT) analysis yielded consistent results (83.5% vs. 85.1%, P  = 0.835). Group TAD demonstrated a significantly superior safety profile (22.6% vs. 46.1% AEs, P  < 0.001). A simplified tegoprazan-based triple therapy is non-inferior to its bismuth-containing counterpart, offering high efficacy with a significantly improved safety profile and reduced pill burden. Chinese Clinical Trial Registry, ChiCTR2500102215. Registered 2025-05-12 (Retrospectively registered).

Hierarchical multi-stage complementary network for medical image denoising

Frictional behaviour of steel–steel and steel–concrete contact surfaces for offshore slip joint applications

Abstract As the energy sector is the main source of anthropogenic greenhouse gas emissions and energy demand is constantly rising, expanding renewable energy sources is imperative. Offshore wind energy is key to this expansion. In the future, more powerful offshore wind farms will be installed in deeper waters. However, this presents new technical and logistical challenges with regard to large-scale substructures. Modular jacket substructures are one possible solution for scalable offshore infrastructure. These require connection systems that are both structurally and technically efficient. Slip joints fulfil these requirements particularly by transferring loads through controlled friction at contacting surfaces rather than through permanent mechanical connectors. This study aims to develop an innovative modular jacket substructure incorporating steel–steel and steel–concrete slip joints. The article focuses on characterising interface behaviour, friction mechanisms, and load-bearing performance across four slip joint material combinations: rolled steel–rolled steel, ground steel–ground steel, rolled steel–concrete, and ground steel–concrete. Surface roughness was quantified using both tactile profilometry and high-resolution 3D scanning, while joint fitting accuracy was assessed exclusively through 3D scan-based geometric analysis. Experimental push-out tests were conducted to determine friction coefficients and load-bearing capacities for each configuration. Additionally, a finite element model was developed to simulate the push-out test and predict the load-bearing capacity. The results revealed that the rolled steel surface exhibited pronounced height fluctuations, irregularity, and distinct macro-waviness. These features promoted mechanical interlocking at the rolled steel–rolled steel interfaces, which in turn led to increasing load resistance and friction coefficients with progressing displacement. In contrast, the other surface combinations exhibited the typical transition from static to kinetic friction. However, the statistical evaluation did not identify significant differences in load-bearing capacity between the material combinations under identical normal stress, and only the rolled steel–rolled steel interface showed a friction coefficient dependent on the applied normal stress. The numerical model captured the observed shear-lag behaviour and reproduced the experimental response with good accuracy. The overall predictive performance of the FE model was demonstrated by a coefficient of determination (R 2 ) of 0.87, a mean absolute percentage error (MAPE) of 16.57%, and a root mean square error (RMSE) of 17.02. Overall, the ground steel–concrete interface proved the most favourable configuration for slip joint applications, as it provided a balanced combination of frictional resistance, stable sliding behaviour, moderate installation forces, and uniform wear characteristics. These features may facilitate assembly and disassembly while maintaining reliable load transfer, making this configuration a promising option for offshore slip joint connections.

Pharyngeal packing effects in elective nasal surgeries: a randomized controlled double-blinded trial

Quercetin nanoparticles exhibit a potential therapeutic effect against the neurochemical changes and motor deficits in a rat model of Parkinson’s disease

Abstract The present study investigated the therapeutic potential of quercetin nanoparticles (QNPs), administered alone or in combination with levodopa/carbidopa (L/C), against reserpine-induced neurochemical alterations and motor dysfunction in a rat model of Parkinson’s disease (PD). Animals were randomly assigned to five experimental groups: a control group, a reserpine-induced PD group, and PD groups treated with QNPs, L/C, or their combination. Motor performance was assessed using the open-field and grid traction tests. Reserpine administration induced marked motor impairments accompanied by significant reductions in dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels in both the striatum and midbrain. These neurochemical deficits were associated with elevated monoamine oxidase (MAO) activity, increased lipid peroxidation (malondialdehyde, MDA), enhanced acetylcholinesterase (AChE) activity, and increased nitric oxide (NO) levels in both brain regions. Additionally, reduced glutathione (GSH) levels were decreased in the midbrain but elevated in the striatum. Treatment with QNPs significantly restored monoamine levels and normalized MAO and AChE activities. Moreover, QNPs markedly attenuated oxidative stress and improved motor performance in reserpine-treated rats. Similarly, L/C administration effectively reversed monoamine depletion, normalized enzymatic activities, and mitigated oxidative stress. Notably, combined treatment with QNPs and L/C produced effects comparable to those observed with either treatment alone, suggesting a lack of additive or synergistic interaction. These findings demonstrate that QNPs exert a significant neuroprotective effect against reserpine-induced motor dysfunction and neurochemical disturbances, supporting their potential as a therapeutic strategy for Parkinsonian pathology.

Prevalence of depression and gender differences in associated factors among empty-nest older adults in rural China

Clinical-guided deep learning framework for diabetic retinopathy: integrating lesion-aware attention, adversarial augmentation, and uncertainty quantification

Clinical-radiomic model development for local recurrence prediction in stereotactic body radiation therapy-treated lung cancer: comparative analysis with radiobiological models

Automated AI-based detection of MRI disease activity in multiple sclerosis: comparison with an expert-adjudicated AI-assisted workflow

Abstract Automated magnetic resonance imaging (MRI) analysis is increasingly used in multiple sclerosis (MS) for cross-sectional quantification of lesion burden and brain structures, as well as for longitudinal detection of new or enlarging lesions; however, its performance in real-world workflows remains incompletely understood. We evaluated agreement between fully automated artificial intelligence (AI)-based detection of MRI disease activity and neuroradiologist-adjudicated AI-assisted assessment in patients with relapsing-remitting MS. In this prospective single-center study, standardized 3T brain MRI was performed at 6-month intervals. Overall, 474 MRI examinations, including 343 follow-up scans from 131 patients, were analyzed. AI-only assessment flagged MRI disease activity more frequently than AI-assisted assessment (11.95% vs. 6.12%; OR 2.01, 95% CI 1.40–2.89), with high overall agreement (Gwet’s AC1 0.90, 95% CI 0.86–0.94). Positive agreement was 54.84% (95% CI 38.42–71.26), whereas negative agreement was 95.51% (95% CI 93.67–97.36). AI-only assessment flagged more new lesions per scan (IRR 2.39, 95% CI 1.36–4.19). Among the evaluated AI-derived lesion volume measures, none was associated with discordance. The reported agreement metrics reflect concordance within an AI-assisted workflow rather than independent validation of AI accuracy. Expert interpretation remains essential for borderline or potentially false-positive AI-flagged findings.

Genome-wide identification of vitamin D receptor-regulated enhancer RNAs reveals epigenetic regulation of CYP24A1 transcription

Extemporaneous dual-drug-loaded contact lenses containing ceftazidime and cefazolin for perforated bacterial keratitis

Impact of maternal education levels and occupation status and their interaction effect on adverse maternal–perinatal outcomes among women with singleton and twin gestations in Hubei, China

Enhanced phytoremediation of heavy metal-contaminated soil and responses of plant-microbial communities in alternating current reactor system

Selection of stable reference genes for accurate RT-qPCR analysis in canine MSCs across tissues, replicative stages, and differentiation states

Sliding mode control of robot manipulators via an improved recurrent neural network and barrier functions

Association between platelet transfusion and acute kidney injury in septic patients with severe thrombocytopenia

Abstract Severe thrombocytopenia frequently occurs in patients with sepsis in the intensive care unit (ICU) and carries a poor prognosis. The safety of prophylactic platelet transfusion in the absence of active bleeding remains debatable. As platelets possess pro-inflammatory and prothrombotic properties, we hypothesized that transfusion may contribute to renal microcirculatory injury and acute kidney injury (AKI). We evaluated whether platelet transfusion and its cumulative dose were independently associated with AKI and mortality in sepsis. We conducted a retrospective cohort study using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (2008–2019). Adults meeting Sepsis-3 criteria with platelet counts below 50 × 10^9/L and no active bleeding were eligible. Patients were classified based on whether they received platelets within 48 h of sepsis onset. The primary endpoint was stage 2 or higher AKI (Kidney Disease: Improving Global Outcomes [KDIGO] creatinine criteria, 7-day window), and the secondary endpoint was 30-day all-cause mortality. We used propensity score matching (PSM) and multivariate logistic regression to account for confounding factors and performed multiple sensitivity analyses to evaluate robustness. Of 1,413 patients included (640 transfused, 773 not), AKI was more frequent in the transfusion group after PSM (64.9% vs. 55.3%; p  = 0.004; adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.15–2.09). A borderline dose-response trend was observed (aOR 1.03 per 1 mL/kg; p  = 0.037), and restricted cubic splines confirmed the linearity (nonlinearity p  = 0.72). Transfusion was not associated with 30-day mortality after adjustment ( p  = 0.877). The direction of the AKI association was consistent across all 12 sensitivity analyses (odds ratio [OR] range 1.12–1.55), including a landmark analysis that excluded patients with AKI onset before their first transfusion (aOR 1.32, p  = 0.044) and pooled estimates from 36 multiply imputed datasets using Rubin’s rules (aOR 1.37, p  = 0.020). When we adjusted for concurrent red blood cell transfusion, the platelet-AKI association was attenuated (aOR 1.24, p  = 0.132), indicating that co-transfusion was a relevant confounder. Prophylactic platelet transfusion in patients with sepsis and severe thrombocytopenia was associated with a higher AKI risk across several analytic approaches. However, the attenuation after blood product adjustment and the limitations inherent to retrospective data prevent us from drawing causal conclusions. These results argue for caution with liberal transfusion and support the need for prospective investigations.

CRISPR-based dual-mode detection of measles virus for laboratory and point-of-care applications

Abstract Rapid, sensitive, and field-deployable diagnostic tools are crucial for effective outbreak management. To address this need, we developed a one-pot, contamination-free assay integrating reverse transcription loop-mediated isothermal amplification (RT-LAMP) with clustered regularly interspaced short palindromic repeats (CRISPR-Cas12a) for the rapid and precise detection of the measles virus (MeV). RT-LAMP primers were designed to target conserved regions of the MeV genome. Reaction conditions—including temperature, MgSO 4, deoxynucleotide triphosphates (dNTPs), and Bst polymerase concentrations—were systematically optimized to achieve robust amplification. CRISPR RNA (crRNA) was designed to target these regions. CRISPR-Cas12a reagents were preloaded into the tube lid. Following RT-LAMP amplification, CRISPR reagents were added to the tubes and mixed by manual shaking. CRISPR-Cas12a demonstrated highly specific target recognition and collateral reporter cleavage activities. Fluorescence detection in laboratory settings and lateral-flow readouts in point-of-care applications were evaluated. Representative sensitivity experiments detected MeV templates down to 10 copies per reaction, while Probit regression analysis estimated LoD 95 of 32.25 copies per reaction, compared with 97.32 copies per reaction RT-LAMP alone. The assay demonstrated high analytical specificity, with no cross-reactivity observed against other common respiratory viruses. The MeV-CRISPR assay was completed within 45–50 min. Overall, this platform provided rapid, sensitive, and specific detection of MeV, showing strong potential for field applications in outbreak surveillance.