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Assessing spatial and temporal transferability of cycleway impact models for bike-share usage in London
Abstract Assessing spatial and temporal transferability in models of cycleway impacts can inform evidence-based transport policies and wider implementation of cycling infrastructure. Yet, limited research on model transferability constrains their practical application in infrastructure planning. This study examines spatial and temporal transferability of models estimating the effects of cycleway implementation on bike-share usage. Using 13 years of fortnightly data from London’s bike-share scheme across Cycleways 1, 3, and 6 (over 14,000 time-station observations), we combine three modelling frameworks (Autoregressive Integrated Moving Average with Exogenous variables [ARIMAX], Generalised Additive Models [GAM], and Generalised Additive Mixed Models with ARMA errors [GAMM+ARMA]) with three transferability strategies (direct transferability, contextual calibration, and local re-estimation). Results show that contextual calibration generally outperforms the other two strategies, reducing errors by 20–80% compared with direct transferability and by 5–45% compared with local re-estimation. Cycleway interventions are positively associated with bike-share usage, whilst demographic covariates exhibit spatial heterogeneity. These findings highlight the value of partial model adaptation for balancing transferability with local relevance and suggest contextual calibration as a practical strategy for transferable cycleway intervention modelling. This study provides insights for transport authorities to prioritise investment, scale cycling infrastructure efficiently, and adapt successful interventions to diverse urban contexts.
Immune Checkpoint Blockade in Deficient Mismatch Repair/Microsatellite Instability–High Gastric Cancer: Solid Evidence or Premature Extrapolation?
Digital motivation for cervical cancer screening: A quasi-experimental trial of the SeDAR Video among middle adulthood Malaysian women
Background Cervical cancer screening (CCS) is a well-established method for preventing cervical cancer (CC). Electronic health (e-health) interventions have shown potential in disseminating health education and are widely used in developed countries to enhance preventive efforts against CC. This study aimed to evaluate the effectiveness of the electronic health video SeDAR® in increasing CCS uptake, knowledge, and motivational factors related to screening. Methods The SeDAR® e-health video was designed based on the Protection Motivation Theory (PMT), incorporating elements such as perceived vulnerability, perceived severity, threat appraisal (fear), coping appraisal, response efficacy, perceived self-efficacy, and protection motivation. It was validated by health experts, media professionals, and female users. A quasi-experimental study was conducted among 76 women, with 38 participants each in the intervention and control groups. The control group received digital pamphlet as intervention tool. Logistic regression was used to assess the impact of SeDAR® on CCS uptake, while repeated measures ANCOVA examined changes in knowledge and motivational constructs. Results The attrition rate of participants is 13.2% with the final sample sizes of 35 (7.9%) and 36 (5.3%) in the SeDAR® and control group, respectively. Participants in the SeDAR® intervention group were significantly more likely to undergo CCS (adjusted odds ratio: 7.26, 95% CI: 1.71–30.74, p = 0.007). While no significant difference was observed in knowledge levels between groups, three motivational constructs showed significant changes. Increases in perceived self-efficacy and protection motivation, along with a reduction in threat appraisal (fear), were associated with greater CCS uptake. Conclusion The SeDAR® e-health video demonstrates effectiveness as a health promotion tool for enhancing motivation and uptake of cervical cancer screening. It offers a promising, scalable approach to support preventive health behavior among women. The authors confirm that all related trials for this intervention are registered under ClinicalTrials.gov with protocol registration number NCT05426642 and release date on June 20, 2022.
Enhanced Reticulospinal Output in Subacute Spinal Cord Injury Patients with Spasticity
In the chronic phase of spinal cord injury (SCI), damage to the reticulospinal and corticospinal tracts has been associated with the development of spasticity. Because spasticity can emerge within just a few weeks postinjury, this suggests that reorganization of these motor pathways may begin during the subacute phase. To test this hypothesis, we assessed the StartReact response—an involuntary release of a planned movement via a startling stimulus that engages the reticulospinal tract—by measuring reaction times from electromyographic activity, motor evoked potentials (MEPs) by stimulating the leg motor cortex using transcranial magnetic stimulation, and maximal voluntary contractions (MVCs) in the quadriceps femoris muscle. Participants included males and females with subacute (1 month post-injury) incomplete SCI with and without spasticity and age-matched controls. Spasticity was evaluated using clinical and kinematic data. We found that patients with spasticity exhibited shorter reaction times to startle stimuli compared with both patients without spasticity and control subjects. In contrast, MEP amplitudes and MVCs were similarly reduced in both SCI groups compared with control subjects. Follow-up assessments conducted in a subset of participants with spasticity at 1 year post-injury revealed persistent exaggerated StartReact responses alongside reduced MEP amplitudes compared with controls. These findings indicate that, in subacute SCI, spasticity is associated with enhanced reticulospinal influences, whereas corticospinal output is reduced regardless of spasticity. The upregulation of reticulospinal pathways, 1 month post-injury, may play a critical role in the development of spasticity.
Integrated anatomical and functional connectivity mapping in episodic migraine: a spectral graph theory approach
Abstract Migraine disproportionately affects women, yet how migraine physiology reshapes large-scale brain communication remains unclear. We combined diffusion-weighted imaging (DWI) and resting-state fMRI in female participants (14 patients with episodic migraine without aura; 15 matched healthy controls) to test how direct and indirect anatomical communication paths in the brain can predict brain function. We used a spectral mapping framework that isolates the contribution of communication paths of a specific length and evaluated how well brain structure predicts brain function within individuals. Analyses of individual path lengths revealed a non-monotonic dissociation: no difference at one-step (direct) paths, but higher mapping accuracy in patients at intermediate indirect scales (four and five steps). At longer scales, contributions attenuated in both groups. Spatial correspondence analyses localized patient-specific effects to default mode network subsystems across multiple atlases. These findings indicate that migraine-related dysfunction reflects altered mesoscale structure-function integration along indirect anatomical routes, and they provide a general approach to dissect structure-function coupling by communication scale in disease.
Body Size and Bladder Cancer Risk: A Pooled Analysis of Prospective Studies From the National Cancer Institute Cohort Consortium
PURPOSE Body size is an established risk factor for several cancers, but associations with bladder cancer risk remain unclear. METHODS We pooled data from 2,533,008 participants in 30 international cohort studies to assess associations of BMI, waist circumference, and height with bladder cancer risk. Multivariable Cox regression models, including smoking status, duration, and other confounders, were run separately by cohort and sex, and results combined by random-effects meta-analysis. RESULTS Incident first primary bladder cancer was diagnosed in 15,259 males and 5,188 females. For males, overweight (BMI, 25.0-29.9 kg/m 2 ) and obesity (BMI, ≥30 kg/m 2 ) were associated with increased risk of bladder cancer, with hazard ratios (HRs) of 1.08 (95% CI, 1.04 to 1.12) and 1.16 (95% CI, 1.10 to 1.22), respectively, when compared with normal weight (BMI, 18.5-24.9 kg/m 2 ). The corresponding HR for females were 1.02 (95% CI, 0.95 to 1.09) and 1.04 (95% CI, 0.95 to 1.14), respectively. The HR per 5 kg/m 2 increment was 1.07 (95% CI, 1.05 to 1.09) for males and 1.00 (95% CI, 0.97 to 1.04) for females. Higher waist circumference was also associated with increased risk of bladder cancer for males (HR per 10 cm increase 1.06 [95% CI, 1.03 to 1.08]) but not females (HR, 1.01 [95% CI, 0.97 to 1.04]). Results for height were largely consistent with those for BMI and waist circumference, with strong and consistent evidence for males, but not females. CONCLUSION Larger body size is associated with increased risk of bladder cancer for males, but not females. Public health interventions to prevent overweight and obesity, along with smoking cessation and reduced occupational exposure to bladder carcinogens, are likely to reduce bladder cancer incidence worldwide.
Advancing inclusion in sports for students with disability: A mixed-methods study on awareness and perspectives toward adaptive sports
Adaptive sports promote inclusion, participation, and well-being in individuals with disabilities. However, limited research has examined the knowledge, awareness, and perceptions of adaptive sports, as well as institutional support and barriers within Saudi universities. An explanatory sequential mixed-methods design was employed. A cross-sectional survey (n = 350; 18.29% reported disabilities; 70.57% females; mean age 28 ± 11 years) assessed knowledge, awareness, perceptions, and perceived barriers to adaptive sports among students, faculty, and administrative staff. Survey findings informed purposive sampling for the qualitative phase, which included focus group discussions with faculty and semi-structured interviews with students with disabilities (SWDs) to contextualize quantitative patterns. The qualitative phase included a focus group discussion, and six interviews were conducted virtually using Microsoft Teams. Participants demonstrated uneven knowledge of adaptive sports (mean score: 8/16). While most correctly recognized their role in enhancing physical education and promoting participation through adapted equipment (>83%), but low understanding of classification (19.71%) and healthcare roles (30.57%). Awareness was low across all domains, particularly in training (75.71% unaware) and participation (80.57% unaware), indicating significant gaps in exposure and education. Although most participants recognized the benefits of adaptive sports, they noted the lack of sufficient policies, accessible facilities, promotion, and staff support. Less than 30% reported inclusive programs, and 16.29% perceived equal funding for parasports training. The key barriers included a lack of awareness (43.14%), inaccessible facilities (41.42%), and limited resources (40%). Interviews with students with disabilities and focus groups with faculty and specialists revealed positive experiences, emphasizing personal growth and social inclusion, but also identified challenges in infrastructure, recruitment, and policy. Despite favorable perceptions, substantial gaps persist in knowledge, accessibility, and institutional commitment. Addressing these issues through awareness campaigns, improved facilities, and inclusive policy development is vital for advancing adaptive sports participation and fostering a culture of inclusion in Saudi higher education.
GNN enhanced reinforcement learning for robot navigation in complex topological networks
Randomized Phase II/III Trial Comparing Hepatectomy, Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603
JCOG0603 demonstrated improved disease-free survival (DFS) with adjuvant mFOLFOX6 after hepatectomy compared with hepatectomy alone in colorectal liver-only metastasis (CRLM), but the overall survival (OS) data were immature. Here, we report OS after long-term follow-up. Eligible patients with colorectal adenocarcinoma and an unlimited number of liver metastases were randomized to adjuvant mFOLFOX6 or hepatectomy alone. DFS was the primary endpoint, and OS was a secondary endpoint. Between March 2007 and January 2019, 151 and 149 patients were randomized to adjuvant chemotherapy and hepatectomy alone, respectively. At a median follow-up of 7.7 years for disease-free surviving patients, 54 (35.8%) and 51 (34.2%) patients had died in the respective arms, (hazard ratio [HR], 1.07 [95% CI, 0.73 to 1.57]). Five-year OS was 73.4% (95% CI, 65.5 to 79.7) and 80.1% (95% CI, 72.6 to 85.7) and 7-year OS was 69.4% (95% CI, 61.2 to 76.2) and 72.4% (95% CI, 64.2 to 79.1), respectively. One patient in the adjuvant chemotherapy arm possibly died of protocol treatment-related toxicity, and one in the hepatectomy-alone arm died of post-protocol treatment complications. Five-year DFS was respectively 49.7% (95% CI, 41.5 to 57.3) and 40.5% (95% CI, 32.5 to 48.3) in the adjuvant chemotherapy and hepatectomy-alone arms (HR, 0.72 [95% CI, 0.54 to 0.97]). Long-term OS did not differ with adjuvant mFOLFOX6 compared with hepatectomy alone in resectable CRLM. Adjuvant mFOLFOX6 may delay recurrence but did not improve long-term survival.
Maximum likelihood estimation of perceptual differences in sorting tasks
Psychophysical paradigms are foundational for quantifying perceptual discrimination. Yet, a persistent trade-off between assessment efficiency and accuracy limits their broad applicability. To address this, we introduce a novel evaluation model grounded in maximum likelihood estimation (MLE) for perceptual sorting tasks. This work details the model’s formulation, validates its performance through simulation, and demonstrates its efficacy in a tactile angle-sorting experiment. Our findings reveal that the sorting paradigm, particularly with five stimuli across three trials, achieves an optimal balance of efficiency and robustness. This method provides a potentially useful and relatively efficient approach for assessing perceptual discriminability within the tactile experimental context, with preliminary indications of its applicability in both research and practical screening.
Association between depression and subjective quality of life among older adults in Japan and Thailand: a cross-cultural multi-group structural equation modeling analysis
Abstract The present study examined the association between depressive symptoms and subjective quality of life (QOL) among older adults in Japan and Thailand. It further analyzed the differences in this structural relationship across cultural contexts. We evaluated the impact of depression on a latent QOL construct and assessed the measurement and structural invariance between the two countries using structural equation modeling (SEM). A cross-sectional survey was conducted among older adults (aged ≥ 60) in urban and rural regions of Japan (n = 88) and Thailand (n = 57). Subjective QOL was assessed using the World Health Organization Quality of Life – Brief Version (WHOQOL-BREF) and modeled as a latent variable comprising five domains. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). SEM with bootstrapping (1,000 resamples) was applied using R and a multi-group analysis was performed to evaluate cross-national differences. Depressive symptoms showed a significant negative effect on latent QOL in the total sample (β = -0.248, p = .008). However, cross-national comparison using chi-square difference test revealed a significant difference in the effect size between Japan (β = -0.49) and Thailand (β = -0.11; Δχ²1= 6.87, p = .008). Thus, measurement invariance was partially supported. Cultural background influences the relationship between depression and QOL. These findings highlight the need for culturally sensitive mental health strategies for older adults.
Reply to: Quality of Chemoradiotherapy in Esophageal Adenocarcinoma Matters
Age differences in the conceptualization and experience of curiosity: A qualitative study
Despite the recent resurgence in research on human curiosity and its influence on knowledge acquisition, there is little consensus on how to operationalize curiosity. Understanding lay beliefs on what curiosity is—and how it is experienced—is therefore an important avenue of study. Furthermore, given age-related shifts in emotional processing and goal-seeking, definitions and experiences of curiosity may fluctuate over the lifespan. Here, we used qualitative techniques to characterize perceptions of curiosity in younger and older adults. We found that while both younger and older adults described curiosity as a form of joyous exploration, younger participants more commonly highlighted the link between curiosity and feelings of deprivation, thrill-seeking, and centrality to being human. Older adults, however, more frequently referenced the social aspects of curiosity, and interestingly, approximately 50% of all participants’ responses were categorized as miscellaneous, suggesting that current multidimensional frameworks of curiosity may not completely align with lay conceptualizations. Older adults were also more likely than younger adults to describe curiosity as a positive trait, indicative of one’s sincerity. In contrast, younger adults more frequently described curiosity as a trait linked to novelty-seeking and personal growth, but that it should be expressed in moderation, likely because of its potentially harmful consequences (e.g., invading others’ privacy). Overall, we show that conceptualizations and experiences of curiosity vary between younger and older adults—an important empirical contribution given the trait’s ubiquity across the lifespan and its role in promoting opportunities for lifelong learning.
TLR7-induced murine inflammation results in a global neuroinflammatory response driving neural circuit-specific transcriptomic changes
Abstract Interactions between the brain and immune system play a key role in the aetiology of brain disorders, with inflammation emerging as a potential causal factor in subsets of major depressive disorder, particularly those resistant to treatment. The mechanisms through which immune activation might drive depressive symptoms remain elusive, limiting the ability to develop new targeted therapies. Using a mouse model of neuroinflammation, involving a TLR7/8 agonist, we combined whole-brain and spatial transcriptomics approaches to determine whether TLR7/8-driven neuroinflammation resulted in consistent immune and neurobiological transcriptional changes throughout the brain. We found evidence of strong immune activation throughout the brain,. and this global inflammatory signal led to regionally specific changes in gene expression. In particular, we found reduced expression of genes associated with synaptic function in brain areas underlying mood and anxiety, such as ventral striatum and amygdala.
Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147)
PURPOSE Detection of molecular residual disease using circulating tumor DNA (ctDNA) may enable postoperative risk stratification and guide adjuvant therapy. We evaluated the prognostic value of a tissue-free, epigenomic ctDNA assay in patients with stage III colon cancer (CC) enrolled in a phase III adjuvant chemotherapy trial. METHODS Plasma samples were collected after surgery and before adjuvant infusional fluorouracil, leucovorin, and oxaliplatin alone or combined with cetuximab. ctDNA was analyzed using a tissue-free assay; in ctDNA-positive patients, tumor fraction (TF) was quantified and genotyping was performed with a 739-gene panel. Associations with disease-free survival (DFS), time to recurrence (TTR), and overall survival (OS) were assessed using multivariable Cox models adjusted for covariates. RESULTS Among 2,260 evaluable patients, 461 (20.4%) were ctDNA-positive with significantly higher detection in advanced T-/N-stage, high-grade, obstruction/perforation, and BRAF V600E tumors. At a median follow-up of 6.1 years, ctDNA positivity was independently associated with shorter TTR (hazard ratio [HR], 5.96 [95% CI, 5.11 to 6.96]), DFS (HR, 5.03 [95% CI, 4.36 to 5.81]), and OS (HR, 4.45 [95% CI, 3.76 to 5.27]; all P < .0001). The 5-year DFS was 27.7% (95% CI, 23.8 to 32.2) v 77.1% (95% CI, 75.1 to 79.1) in ctDNA-positive versus ctDNA-negative patients, and adverse prognostic impact was greater in lower T/N stage, low-risk, and dMMR subsets (interaction P = .0012-.041). Among ctDNA-positive patients, TF was nearly double in those who recurred or died ( P = .0002) and stratified patients for TTR, DFS, and OS (all adjusted P < .002). Genotyping identified mutations in FLT1 (OR, 8.99) and PREX2 (OR, 7.73) genes that were most strongly associated with recurrence ( P < .03). CONCLUSION Evaluation of ctDNA in resected stage III CC using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, dMMR, and specific mutations defined poor prognostic groups among ctDNA-positive patients.
Editorial Note: A scalable blockchain-enabled federated learning architecture for edge computing
Structure-guided analysis of divergent homologs unveils deep ancestry and arthropod specialization of the pacifastin family
Abstract The Pacifastin family has been widely regarded as an arthropod-specific innovation, functionally restricted to the regulation of innate immunity. Here, we challenge this paradigm using a structural phylogenomics approach that overcomes the sequence erosion characteristic of small disulfide-rich proteins. We identified a population of “cryptic” homologues comprising ~ 30% of the dataset—undetectable by sequence alone and demonstrated that the characteristic Pacifastin’s six-cysteine scaffold is not an arthropod invention but an ancient lineage whose evolutionary roots extend across major metazoan phyla, Fungi, and Bacteria. Structural and architectural profiling revealed two recurrent organizational modes: an ancestral class characterized by an N-terminal β-hairpin extension, glycine-rich and frequently embedded in multidomain, extracellular matrix–associated proteins, and a conventional, derived arthropod-restricted class characterized by modular simplification and predicted structural rigidity consistent with a soluble-effector function. We propose a "Liberation and Structural Convergence" evolutionary model to explain this transition: the acquisition of proteolytic processing sites in inter-domain linkers is consistent with a mechanism by which arthropods may have released these domains from the matrix, while the concurrent structural convergence is consistent with adaptation to a soluble, circulating hemolymph environment. Further phylogenomic profiling of the reactive site revealed a functional shift from an ancestral inhibitory signature enriched in basic and charged residues to a derived arthropod-specific radiation toward hydrophobic residues. This transition suggests a broadening of target specificity toward chymotrypsin- and elastase-like proteases, consistent with the recruitment of these inhibitors into arthropod immune roles. Together, these results reposition pacifastins as an ancient protein lineage and illustrate how modularity, proteolytic processing, and biophysical constraints may have driven the transition from matrix-embedded regulatory scaffolds to systemic soluble effectors.
Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial
PURPOSE To evaluate the efficacy and safety of adjuvant hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous (IV) fluorouracil/leucovorin (LV5FU2) after curative-intent surgery of ≥4 colorectal liver metastases (CRLM). METHODS Patients with an Eastern Cooperative Oncology Group performance status 0-1, who underwent resection or ablation of ≥4 CRLM after preoperative IV chemotherapy were enrolled. Patients were randomly assigned (1:1) to receive adjuvant oxaliplatin via HAI (HAI group, n = 50) or IV infusion (IV group, n = 49), both combined with IV LV5FU2 for at least 3 months. The primary end point was hepatic recurrence-free survival (h-RFS). Secondary end points included RFS, overall survival (OS), safety, and feasibility. RESULTS After a median follow-up of 59 months (IQR, 45-71), the median h-RFS was 25 (95% CI, 16 to 37) months in the HAI group versus 12 (95% CI, 8 to 19) months in the IV group (hazard ratio [HR], 0.63 [95% CI, 0.40 to 0.99]; P = .047). Median RFS was 14 months (95% CI, 10 to 20) in the HAI group versus 9 months (95% CI, 7 to 11) in the IV group (HR, 0.63 [95% CI, 0.41 to 0.97]; P = .03). Median OS was 74 months (95% CI, 51 to not defined) in the HAI group versus 57 months (95% CI, 37 to 69) in the IV group (HR, 0.61 [95% CI, 0.33 to 1.12]; P = .11). Five-year OS was 62% in the HAI arm compared with 47% in the IV arm. Grade 3 to 4 adverse events occurred in 58% of HAI patients and 32% of IV patients ( P = .02). No treatment-related deaths were reported. Four or more cycles of adjuvant chemotherapy were delivered in 81% of patients in the HAI group and 78% in the IV group ( P = .75). CONCLUSION Adjuvant oxaliplatin HAI plus LV5FU2 improves h-RFS after curative-intent surgery of CRLM in high-risk patients, with an acceptable safety profile. These results support further evaluation in a phase III trial.
Birth in shelters: Midwives’ lived experiences in providing childbirth care amidst war in Gaza
Background The warfare against the Gaza Strip in the occupied Palestinian territory, starting in October 2023, caused massive destruction of infrastructure, including homes and hospitals. Within two years (October 2023 to October 2025), most of the 2.1 million inhabitants were displaced, and more than 69,500 people were directly killed, of whom more than 70% were women and children. To enhance preparedness in maternal care during war, it is important to understand how midwives respond to emergencies in conflict zones. This study seeks to explore the experiences of midwives in delivering childbirth care to women in Gaza within shelters, tents, and amidst the rubble during wartime. Materials and methods We employed a descriptive qualitative phenomenological design. We used a purposeful snowball sampling approach to identify midwives who had assisted women in giving birth in shelters or tents during the war. Face-to-face in-depth interviews were conducted with nine midwives between January and April 2025, and underwent reflexive thematic analysis. Results An overarching theme was identified: “Midwives torn between fear and professional compassion while struggling for humanity in a ruthless war”. Three additional themes were developed: “Unprotected in ruthless warfare”, “Professional role and contradictive emotions”, and “Challenges and potentials for midwives during war and emergencies”. Conclusions The study recommends the development of clear preparedness policies aligned with midwives’ scope of practice that support their professional role when caring for pregnant women in war, emergency, and humanitarian contexts. Given the volatile context of the oPt, Palestinian midwives should be actively involved in preparedness strategies for emergency response. They need guidance, support, necessary supplies, connection to backup resources, and training to assist births safely outside hospital settings.