Browse Articles

A cell cycle-dependent transition of acetylation to phosphorylation regulates timely centrosome maturation

Visual analytics framework for survival analysis and biomarker discovery from gene expression data

We introduce a visual analytics methodology for survival analysis, and propose a framework that defines a reusable set of visualization and modeling components to support exploratory and hypothesis-driven biomarker discovery. Survival analysis—essential in biomedicine—evaluates patients‘ survival rates and the onset of medically relevant events, given their clinical and genetic profiles and genetic predispositions. Existing approaches often require programming expertise or rely on inflexible analysis pipelines, limiting their usability among biomedical researchers. The lack of advanced, user-friendly tools hinders problem solving, limits accessibility for biomedical researchers, and restricts interactive data exploration. Our methodology emphasizes functionality-driven design and modularity, akin to combining LEGO bricks to build tailored visual workflows. We (1) define a minimal set of reusable visualization and modeling components that support common survival analysis tasks, (2) implement interactive visualizations for discovering survival cohorts and their characteristic features, and (3) demonstrate integration within an existing visual analytics platform. We implemented the methodology as an open-source add-on to Orange Data Mining and validated it through use cases ranging from Kaplan–Meier estimation to biomarker discovery. While the framework is generally applicable, we illustrate its value through case studies in cancer research, where survival analysis is of critical importance. The resulting framework illustrates how methodological design can drive intuitive, transparent, and effective survival analysis.

Network model for alignment, stitching and slice-to-volume 3D reconstruction of large-scale spatially resolved slices

The risk assessment of sleep duration on geriatric sarcopenia and its regulatory role in the effect of BMI index on geriatric sarcopenia based on the CHARLS database

Background The effect of sleep duration on geriatric sarcopenia remains unclear, and evidence of the combined impact of it and BMI on geriatric sarcopenia is scarce. Aims To conduct the risk assessment of sleep duration on geriatric sarcopenia and explore its moderating role in the effect of BMI on geriatric sarcopenia based on the CHARLS database. Methods Data were extracted from the China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015 waves respectively. Logistic regression and Cox regression analyses were conducted to assess the risk of sleep duration for geriatric sarcopenia, and the regulatory effect of sleep duration on the association between BMI and sarcopenia. Subgroup analysis was conducted to enhance the stability of the results. Results The four abnormal types of sleep duration were significantly associated with sarcopenia. A significant association between obesity and decreased risk of sarcopenia was observed in sufficient sleep and sleep deprivation groups after the full adjustment of covariates (Adjusted HR = 0.25, 95%CI: 0.10–0.64, P < 0.001; Adjusted HR = 0.13, 95%CI: 0.03–0.53, P = 0.004; Adjusted HR = 0.26, 95%CI: 0.10–0.66, P = 0.005), and relationships of underweight and overweight with sarcopenia were observed in sufficient sleep, sleep deprivation, and mild oversleeping groups. In the group of oversleeping, the associations were not significant. Conclusion Abnormal sleep durations including sleep deprivation and oversleeping are linked to a heightened risk of sarcopenia among older adults. Underweight is associated with the increased sarcopenia risk, and overweight is correlated with the decreased risk of sarcopenia, especially in females with abnormal sleep duration except for severe oversleeping, and obesity is associated with the decreased risk of sarcopenia, especially in adults aged over 65 with sleep deprivation.

International testing and refinement of AI algorithms predicting acute leukemia subtypes from routine laboratory data

Abstract Despite advances for patients with acute leukemia health disparities limit access to diagnosis and treatment. Artificial Intelligence (AI) approaches may address some disparities. We retrospectively assemble a diverse, international cohort of 6206 leukemia patients from 20 centers to test an AI tool designed to support leukemia diagnosis using standard laboratory results. Executing the pretrained algorithm results in varying accuracy metrics. With confidence cutoff predictions, 2000-fold bootstrapped area under the curve (AUROC) metrics are 0.94 for acute myeloid leukemia (AML), 0.98 for the promyelocytic subtype and 0.84 for acute lymphoblastic leukemia. However, this cutoff excludes 70.8–92.5% of patients from predictions. We improve accuracy and robustness, while maintaining generalizability via an ensemble of Isolation Forest and Local Outlier Factor increasing AUROC for AML from 0.72 to 0.84 (hold-out test set, patients below confidence threshold), while excluding only 12.1% of patients. Furthermore, we retrain the algorithm for pediatric patients.

Exploring factors influencing parents’ adoption intention toward children’s illustrated e-books: A push-pull model perspective

With the development of multimedia technologies, children’s illustrated e-books are getting increasingly popular due to their diverse formats and engaging content. However, few studies have explored the factors influencing parents’ adoption intention toward illustrated e-books for children. This research aims to address this gap by employing the push-pull model to explore the influences of pull factors (i.e., relative advantages, perceived trialability, perceived enjoyment, variety-seeking), push factors (i.e., vision health stress, evaluation cost), and individual characteristics (i.e., age, gender, experience of use) on parents’ adoption intention toward illustrated e-books for children. Data were collected from 348 parents in China and analyzed using structural equation modeling (SEM). The research results suggest that perceived enjoyment and variety-seeking are important pull factors, while evaluation cost serves as a vital push factor. Moreover, children’s gender significantly influences the adoption intention. Parents of boys demonstrated a higher adoption intention than parents of girls. These nuanced insights have practical implications for designers of illustrated e-books for children.

Modulating coordinate site occupancy in high-entropy spinel electrocatalysts

Cancer risk associated with DPP4 inhibitors in type 2 diabetes: A pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS)

Background The use of dipeptidyl peptidase 4 (DPP4) inhibitors in treating type 2 diabetes mellitus (T2DM) is increasingly widespread. However, their association with malignancy risk has not been comprehensively evaluated in real-world clinical settings. This study, utilizing the Food and Drug Adverse Event Reporting System (FAERS) database, investigated the potential link between DPP4 inhibitors and malignancies. Methods Data from the FAERS database (January 2019 to December 2024) were analyzed. Descriptive statistics assessed patient demographics for each drug-event combination, while disproportionality analysis based on Reporting Odds Ratio (ROR) and Information Component (IC) metrics valuated cancer-related adverse event (AE) risks. Binary logistic regression was used to minimize potential bias. Results A comprehensive analysis identified 3,764 AE reports linked to malignancies in T2DM individuals treated with DPP4 inhibitors. Signal detection analysis revealed that sitagliptin exhibited the strongest and most extensive positive signals across both the Preferred Terms and Standardized Medical Dictionary for Regulatory Activities Queries. Specifically, significant signals were observed for malignancies (ROR 025 : 13.80, IC 025 : 3.48), tumor lysis syndrome (ROR 025 : 5.79, IC 025 : 2.32), and site-specific neoplasms (e.g., uterine, fallopian tube, and prostate). Age distribution analysis indicated that the median age of individuals reporting malignancy-related AEs exceeded 70 years in most drug groups. Furthermore, in studies with larger sample sizes, the median time to AE onset for for DPP4 inhibitors ranged from 13 to 15 months. Conclusions This study demonstrates significant associations between all five DPP4 inhibitors and malignancy-related AEs, with sitagliptin showing the highest risk profile. These findings highlight the need for further validation through large-scale prospective studies to verify the observed pharmacovigilance signals and to elucidate their potential clinical significance and underlying biological mechanisms.

Ultra-precision deconvolution of spatial transcriptomics decodes immune heterogeneity and fate-defining programs in tissues

Global COI meta-analysis reveals ocean-basin genetic structure in Sphyrna lewini

The scalloped hammerhead shark ( Sphyrna lewini ) is a circumglobally distributed apex predator clarified as Critically Endangered due to population declines exceeding 80%. Understanding population structure is essential for effective conservation management, yet comprehensive genetic surveys across the species’ range remain limited. We conducted a meta-analysis of all publicly available cytochrome oxidase I (COI) sequences for the family Sphyrnidae from the Barcode of Life Database (BOLD), applying a hierarchical analytical approach that examined haplotype clustering patterns across all hammerhead species. This family-level analysis enabled detection of taxonomic inconsistencies invisible to single-species queries: 18 of 1,066 samples (1.7%) carried species labels inconsistent with their haplotype assignments, with S. zygaena comprising the majority of mislabeled specimens in S. lewini haplotypes. Among 595 confirmed S. lewini samples, we identified four haplotypes forming two distinct phylogenetic groups with 94.6–96.2% sequence identity across a 184 bp COI fragment. Geographic analysis of 65 S. lewini samples with precise coordinates revealed pronounced ocean basin-scale segregation. Haplotype Group A (h1 and h4) predominated in the Indian Ocean, Atlantic basins, and South Pacific, while Group B (h15 and h2) is centered in the western Pacific. Country-level metadata for all 595 samples supported this pattern, with Indonesia harboring both groups consistent with its position at the Indian-Pacific biogeographic boundary. The rare haplotype (h15; n = 5) restricted to the North Atlantic included depositor notes indicating “possible cryptic species”. These findings reveal ocean basin-scale partitioning in S. lewini with implications for defining management units in this threatened species.

Formaldehyde hydrazone as a methyl reagent for nickel-catalyzed cross-coupling methylation of aryl and heteroaryl electrophiles

Effect of maternal education on the literacy-numeracy development of children: A propensity-score matched analysis

This study examined the causal relationship between maternal education and children’s literacy-numeracy development in Bangladesh using nationally representative data from the Bangladesh Multiple Indicator Cluster Survey. The analysis focused on 9,454 children aged 3–4 years. To strengthen causal inference, we applied propensity score matching, which reduces selection bias by balancing observed covariates between groups. From the analysis, we found that the average treatment effect of the treated was almost 18.4%, which means after matching, the probability of literacy-numeracy development in children was 18.4% higher among the mothers who had higher level of education compared to the same mothers had they not higher level of education. Subgroup analyses further revealed heterogeneity by place of residence: the effect of maternal education was stronger in urban areas (26.2%) than in rural areas (16.3%), suggesting that contextual factors may amplify or constrain the benefits of maternal education. These findings provide an evidence of the critical role of maternal education in early childhood development.

Structural basis for prostaglandin and drug transport via SLCO2A1

Abstract Organic anion-transporting polypeptide transporters (SLCO/OATPs) function as cellular gatekeepers, regulating intestinal absorption, hepatic and renal clearance, and the tissue distribution of drugs and metabolites in the human body. However, the mechanisms underlying substrate selection within the SLCO superfamily remain unclear, hampering efforts to rationalize the interaction of drugs and metabolites with these transporters. SLCO2A1 (also known as OATP2A1) is responsible for the distribution of eicosanoids, including prostaglandins (PGs) and thromboxanes, throughout the body, in addition to several families of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we present cryogenic electron microscopy structures of SLCO2A1 bound to endogenous PGs and to four widely prescribed medications for treating inflammation, chronic asthma, and Parkinson’s disease (PD). Complementary molecular dynamics and in vivo cellular assays elucidate the molecular basis for PG and drug recognition. Our study reports essential mechanistic details that underpin substrate selection and subfamily adaptation within the broader SLCO superfamily of drug and metabolite transporters.

Visual self-assessment of dental appearance: A comparison of mirror types and digital reflection via smartphone front facing camera

Introduction In dental practice, patients often evaluate their own dental attractiveness using mirrors or smartphone digital reflections. This study aimed to investigate how mirror size, shape, magnification and smartphone-based digital reflection influence self-perceived dental attractiveness. Materials and methods This was a prospective cross-sectional study. Eighty-three participants assessed their dental attractiveness using a randomised sequence of reflective devices, including mirrors of different sizes (full-length, medium, small, standard pocket), a magnified pocket mirror, a tooth-shaped mirror, and a smartphone front-facing camera. Ratings were recorded on a 10-point visual analogue scale. Data were analysed using repeated-measures ANOVA with Bonferroni-adjusted post hoc comparisons. Intra-rater reliability was evaluated in a subset of participants using the intraclass correlation coefficient (ICC). Results Repeated-measures ANOVA indicated a significant overall effect of device type on dental attractiveness (F(4.62, 378.83) = 15.57, p < 0.001). Post hoc analyses showed no significant differences among full-length, medium, small, and standard pocket mirrors, or between these mirrors and the smartphone reflection (all p > 0.05). The magnified pocket mirror and tooth-shaped mirror were rated significantly lower than other devices (p < 0.001). Intra-rater reliability was generally poor (ICC < 0.35), with only the medium-size and tooth-shaped mirrors showing moderate agreement (ICC = 0.59 and 0.63, respectively). Conclusion Reflective device type influences self-perceived dental attractiveness. Standard mirrors of different sizes and smartphone reflections produced similar and generally favourable ratings. In contrast, magnified and tooth-shaped mirrors yielded lower ratings. Poor intra-rater reliability suggests that self-assessment based on reflection alone is inconsistent.

Copper single-atom nanozyme with intelligent capture and photo-enhanced activity for controlling plant bacterial diseases

A theoretical and experimental model of flow characteristics in subretinal injections

Subretinal injections (SI) are used to deliver gene therapies for inherited retinal diseases, yet the optimal injection parameters remain undefined. This study used theoretical and experimental models to quantify the relationship between injection pressure, flow dynamics, and residual flow. A theoretical model (TM) was developed based on the Hagen-Poiseuille law and the theory of a jet immersed in the same liquid. An experimental model (EM) was constructed to allow for measuring flow and residual flow across injection pressures ranging from 0 to 20 psi. We assessed the effects of ambient pressure, injection system tubing length, and syringe priming technique. A minimum pressure of 6 psi was required to generate a detectable flow in the EM. Jet speed increased with the square root of injection pressure, aligning with theoretical predictions. Residual flow persisted for 28–47 seconds after injection and increased logarithmically with injection pressure. Elevated ambient pressure (45 mmHg) only reduced flow at lower injection pressures. The “lock-and-load” priming method decreased jet speed and increased residual flow compared to the “load-and-lock” method. Both TM and EM quantified SI flow dynamics, with EM demonstrating residual flow at all tested pressures. To minimize complications, clinicians should use the lowest injection pressure and allow sufficient time for the cannula to be withdrawn from the subretinal space.

Parvalbumin-positive neurons in the medial septum participate in the formation of hippocampal-dependent spatial memory

IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) in UK primary care: An internal pilot for a cluster randomised controlled trial

Introduction Supported self-management that includes a personalised asthma action plan and regular professional review, reduces unscheduled consultations, and improves asthma outcomes and quality of life. However, despite unequivocal inter/national guideline recommendations, supported self-management is poorly implemented in UK primary care. The IMPlementing IMProved Asthma self-management as RouTine (IMP 2 ART) implementation strategy (including facilitated provision of patient, professional, and organisational resources) has been developed to address this challenge and is being evaluated in a UK-wide cluster randomised controlled trial (cRCT). The internal pilot aimed to assess the trial recruitment processes, delivery of and general practice engagement with the implementation strategy to inform the progression criteria. Methods Using mixed methods, we recruited 12 general practices and monitored trial processes and IMP 2 ART delivery through team logs and automated data (e.g., use of patient online resources; uptake of practice education modules). Qualitative interviews with general practice staff and IMP 2 ART facilitators explored feasibility and acceptability of the implementation strategy. Results We randomised 12 general practices to the IMP 2 ART implementation strategy arm (n = 6) or usual asthma care (control, n = 6). One control practice withdrew post-randomisation following concerns about data sharing. Most components were delivered successfully to the implementation group practices so that we met our progression criteria. In all six practices, the facilitated workshop was arranged within 12 weeks of randomisation and the team education module was completed (median 11 accesses/practice), the in-depth module was completed by ‘the healthcare professional responsible for asthma reviews’ (range 3-7 professionals/practice), and the asthma review template was successfully downloaded to the practice system. All six implementation practices received the baseline and first monthly audit and feedback report although there were delays in this process due to national-level governance changes. Practices’ perceptions of IMP 2 ART were encouraging. In general, they participated in the patient, professional and organisational implementation strategies and reported positive experiences of the trial. Conclusions The study provides evidence that the IMP 2 ART trial is feasible, and the implementation strategy is acceptable with only minor adjustments to trial processes. The IMP 2 ART strategy is now being tested in a UK-wide cRCT [ref: ISRCTN15448074], evaluating implementation (action plan ownership) and health outcomes (unscheduled care).

Functional and structural basis of a negative allostery within GABAB hetero-tetramers

Impact of contralateral sensorineural hearing loss on prognosis in idiopathic sudden sensorineural hearing loss

Objective The aim of this study was to investigate the impact of contralateral sensorineural hearing loss on prognosis in idiopathic sudden sensorineural hearing loss. Methods A retrospective analysis was conducted on 445 ISSNHL patients treated between January 2020 and January 2024. The patients were divided into two groups: recovery (234 cases, including complete and partial recovery) and no-recovery (211 cases, no recovery). Pure-tone audiometry was used for evaluation. Clinical characteristics were compared between the groups, and multivariate logistic regression was performed to identify risk factors for poor prognosis. Results Significant differences were observed between the two groups regarding contralateral hearing level, age, duration of illness, diabetes, hypertension, and audiometric curves. An increase in the hearing threshold of the contralateral ear was positively correlated with the risk of ineffective treatment. Patients with contralateral sensorineural hearing loss prior to the onset of ISSNHL exhibited a 2.757-fold increased risk of treatment failure compared with ISSNHL patients who had normal contralateral ear hearing. Multivariate logistic regression analysis revealed that contralateral sensorineural hearing loss exhibited a significant multiplicative interaction with age over 60 years, hypertension, and a disease duration exceeding 4 days. Conclusion The presence of contralateral sensorineural hearing loss before the onset of ISSNHL is an independent risk factor for poor prognosis in ISSNHL. It interacts significantly with age over 60 years, hypertension, and disease duration exceeding 4 days. A thorough assessment of contralateral hearing status, in conjunction with factors such as age, hypertension, and disease duration, is essential for developing personalized treatment plans to improve prognosis.