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Embankment-related roadway departure crashes pose significant safety risks due to slope geometry, vehicle instability, and elevated impact forces, yet limited research addresses how injury mechanisms vary across roadway environments and over time. This study examines embankment-related crash severity using Texas Crash Records Information System (CRIS) data from 2021 to 2024, employing a hybrid framework combining Random Parameters Logit models with Heterogeneity in Means (RPLHM), partially constrained temporal stability testing, and Natural Language Processing (NLP) based narrative analysis. The framework captures persistent and time-varying effects of roadway geometry, environmental conditions, crash characteristics, and driver attributes across three severity outcomes: no injury, possible/non-incapacitating injury, and fatal/incapacitating injury. Results reveal that roadway alignment, lighting conditions, fixed-object involvement, and occupant protection consistently shape severity, while heterogeneity in geometric and environmental factors indicates strong context-dependent risk patterns. Curved alignments and certain roadway environments increase the likelihood of severe injury, whereas seatbelt use substantially increases the probability of non-injury, though its protective effect varies across contexts. Temporal analyses show that while several determinants remain stable, selected parameters exhibit year-specific variation. Narrative topic modeling highlights recurring mechanisms involving loss of control, slope interaction, and environmental influences. These findings underscore that uniform countermeasures are insufficient and emphasize, the need for context-specific roadside design, slope treatment, speed management, and occupant protection strategies.

Clear aligner therapy has expanded substantially in mixed dentition, yet the boundaries of clinical predictability across indications, movement types, and growth stages remain incompletely defined. The aim of this review was to synthesize evidence on clear aligner therapy in mixed dentition, describe indication-specific performance patterns, and identify evidence gaps that limit clinical confidence. This scoping review was reported in accordance with PRISMA-ScR. PubMed/MEDLINE, Embase, and Scopus were systematically searched for studies published from 2000 to 2025. Additional records were identified through Google Scholar and reference list searching. Randomized controlled trials, prospective and retrospective cohorts, and cross-sectional studies were eligible. Data were charted and synthesized descriptively. Fifty-nine studies were included (8 randomized controlled trials, 11 prospective cohorts, 38 retrospective cohorts, 2 cross-sectional), most involving children aged 7 to 12 years. Achieved transverse dentoalveolar expansion with clear aligners was lower than planned, particularly posteriorly and at gingival levels. Comparative studies suggested greater posterior and palatal changes with rapid maxillary expansion. Mandibular advancement aligners were associated with Class II sagittal improvement, with responses varying by skeletal maturity and dentoskeletal pattern. Evidence for incisor correction, molar movement, vertical outcomes, airway, oral health, patient-reported outcomes, and smile esthetics remained limited. Clear aligners in mixed dentition demonstrate indication-dependent predictability influenced by movement type, anatomical region, and growth stage. Clinical confidence remains limited by retrospective evidence, heterogeneous outcome measures, and insufficient standardized reporting of post-treatment stability.

Phosphorylation is one of the most prevalent and dynamic post-translational modifications. It regulates aspects of cellular signaling, metabolism, and disease progression. Comprehensive characterization of phosphoproteins and their phosphorylation remain analytically challenging due to their low abundance, the dynamic nature of the phosphorylation, substoichiometric modification levels, and the complexity of biological matrices. However, recent advancements in enrichment strategies have substantially increased the depth and precision of phosphoproteomics analyses using mass spectrometry. Strategies such as immobilized metal ion affinity chromatography and metal oxide affinity chromatography refine the selective isolation of phosphorylated peptides from complex mixtures. Emerging materials, such as advanced metal nanoparticles, MXenes, and carbon-based nanostructures, are increasingly being used in phosphoproteomics enrichment due to their inherent features such as high surface areas, easily tunable surface chemistry, and strong structural stability, which provide enhanced enrichment efficiency and selectivity. Here, we outline strategies and innovations in phosphoprotein enrichment materials in quantitative proteomics MS platforms.

Plastic waste from healthcare is an increasing environmental challenge, particularly in resource-intensive clinical pathways such as dialysis. Peritoneal dialysis (PD) generates large quantities of single-use plastic materials, making its waste stream a priority for sustainable intervention. Conventional disposal through incineration contributes substantially to greenhouse gas emissions (GHG) and produces hazardous ash. Pyrolysis, a chemical recycling process that converts mixed plastic waste into usable outputs, has been proposed as a lower-carbon alternative. This study aimed to estimate the change in GHG emissions and key environmental co impacts if a hospital nephrology service were to switch its PD plastic waste treatment from incineration to pyrolysis. A comparative life cycle assessment (LCA) was conducted for the management of 1 kg of plastic waste from PD. OpenLCA modelling with established life cycle inventory datasets was used to quantify environmental impacts across multiple categories. Two scenarios were assessed: full incineration and a combined system in which pyrolysis was used with a 10% residual fraction sent to incineration. Impact categories included climate change, freshwater ecotoxicity, marine eutrophication, human toxicity, mineral resource use and water consumption. Sensitivity Analysis were also undertaken. The combined pyrolysis system with 10% residual incineration generated a net climate change impact of -0.230 CO₂e per kg of healthcare plastic waste managed, compared with +1.996 CO₂e per kg under full incineration. Across all sixteen environmental impact categories assessed, the pyrolysis pathway demonstrated lower impacts than conventional incineration. Pyrolysis generated net environmental credits in seven categories, including climate change, non-renewable energy use, freshwater eutrophication and photochemical oxidant formation. Pyrolysis shows clear potential as a lower-carbon alternative for managing plastic waste from PD and could support efforts to align clinical waste management with broader sustainability goals. Despite these environmental advantages, economic constraints and differing national regulations currently limit widespread adoption. The findings indicate that pyrolysis may play an important role in reducing the environmental burden of plastic waste in high-volume clinical services. Further work is needed to evaluate the operational feasibility of this approach and to position pyrolysis within a wider set of sustainable waste management strategies.

Medical dramas are widely consumed by medical students globally and may constitute an informal or hidden curriculum influencing professional identity, empathy, and ethical reasoning. Palestinian medical students represent an understudied population navigating a resource-constrained and geopolitically complex healthcare context. To investigate the perceptions of Palestinian medical students regarding medical dramas, including viewing habits, assessments of clinical and ethical realism, psychological and behavioural impacts, and the potential role of such media as an informal educational resource. A cross-sectional study was conducted among 638 undergraduate medical students from five universities in the West Bank, Palestine, using convenience and snowball sampling. Data were collected via an online structured questionnaire adapted and culturally validated from the Czarny et al. (2008) instrument, incorporating forward-back translation, pilot testing (n&#x2009;=&#x2009;15), and internal consistency assessment (Cronbach's alpha&#x2009;=&#x2009;0.81). Descriptive statistics and Chi-square tests were applied. Mean age was 21.1&#x2009;&#xb1;&#x2009;1.65 years; 66.8% were female. Most participants (73.4%) had watched medical dramas, primarily via digital streaming platforms. While 77.3% perceived clinical scenes as only slightly or moderately realistic, 41.9% considered ethical content to be moderately accurately depicted. Approximately 46.6% reported increased empathy and 47.2% reported increased study motivation. Drama viewers were significantly more likely to rate informal sources-family (p&#x2009;<&#x2009;0.001), friends (p&#x2009;=&#x2009;0.021), and online news (p&#x2009;=&#x2009;0.037)-as important for ethical guidance, compared with non-viewers. Palestinian medical students engage substantially with medical dramas and appraise their content critically. Associations between drama viewing and increased empathy, study motivation, and reliance on informal ethical guidance sources suggest a potential hidden-curriculum effect. Given the cross-sectional design and convenience sampling, causal inferences cannot be drawn. These findings support cautious integration of medical dramas into bioethics and professionalism curricula as supplementary teaching tools.

Urban transport affordability remains a major policy concern in rapidly urbanizing Sub-Saharan African cities. Despite extensive theoretical work on transport economics, empirical evidence quantifying structural determinants of perceived public transportation cost in secondary African cities remains limited. This study examined the association between economies of scale, road maintenance and upkeep, fuel and energy subsidy, and fare infrastructure integration on perceived public transportation cost in Adama City, Ethiopia. A cross-sectional study was conducted among transport associations, driver training institutions, and regulatory officials (n&#x2009;=&#x2009;181; response rate 88%). Data were analysed using multiple linear regression. The regression model was statistically significant (F (4,176)&#x2009;=&#x2009;63.42, p&#x2009;<&#x2009;0.001) and explained 59% of the variance in transportation cost (R&#xb2; = 0.59; adjusted R&#xb2; = 0.57). Economies of scale showed the strongest inverse association (&#x3b2; = -0.41, p&#x2009;<&#x2009;0.001), followed by fuel and energy subsidy (&#x3b2; = -0.29, p&#x2009;<&#x2009;0.01), road maintenance (&#x3b2; = -0.18, p&#x2009;<&#x2009;0.05), and fare infrastructure integration (&#x3b2; = -0.16, p&#x2009;<&#x2009;0.05). Structural and policy-level interventions targeting system scale, infrastructure quality, and coordinated fare systems may substantially reduce perceived urban transport costs. The findings contribute empirical evidence from Ethiopia to the broader literature on urban transport economics.

Accurate segmentation of high-resolution images requires the simultaneous preservation of fine-grained spatial details and the modeling of long-range contextual dependencies. Conventional convolutional neural networks efficiently capture local structures but are limited by restricted receptive fields, whereas transformer-based architectures provide global context at the cost of quadratic computational complexity. Recent selective state-space models (SSMs), particularly Mamba-based architectures, offer an attractive alternative by enabling global dependency modeling with linear computational complexity. However, existing vision-oriented implementations largely rely on empirical architectural choices, resulting in fragmented design strategies and limited reproducibility. Here, we introduce Selective State-Space U-Net (SSS-U-Net), a unified architectural framework that systematically formalizes the integration of selective state-space dynamics within encoder-decoder segmentation networks. The proposed framework establishes a comprehensive taxonomy of three macro-integration topologies-sequential, parallel, and bottleneck state-space routing-and defines multi-directional spatial scanning mechanisms that preserve two-dimensional structural coherence while leveraging one-dimensional state-space representations. Furthermore, we provide a standardized design protocol that maps continuous-time selective state-space dynamics onto high-resolution visual domains while maintaining strict linear-complexity scaling. The framework is validated across representative biomedical and industrial imaging benchmarks, including Kvasir-SEG for polyp segmentation and MVTec AD for anomaly detection. Experimental evaluation demonstrates strong predictive performance, achieving 94.2% mean Dice score on Kvasir-SEG and 98.6% pixel-level AUROC on MVTec AD, while maintaining substantially lower memory consumption and computational overhead than attention-based alternatives. Ablation analyses further reveal the complementary roles of selective state-space gating, multi-directional scanning, and hybrid CNN-Mamba feature fusion in improving segmentation fidelity and anomaly localization. These findings establish a reproducible architectural blueprint for integrating selective state-space models into dense prediction systems and provide practical design guidelines for scalable high-resolution image analysis across biomedical, industrial, and resource-constrained vision applications.

Standing sedation is frequently required in donkeys for minor surgical and diagnostic procedures, yet information on the cardiac safety of &#x3b1;2-adrenoceptor agonists and opioid combinations in this species is limited. This study evaluated the echocardiographic effects of intravenous medetomidine, butorphanol, and their combination in clinically healthy donkeys. Sixty donkeys were randomly assigned to four groups (n&#x2009;=&#x2009;15/group) to receive intravenous saline (control group, CG), medetomidine group (10&#xa0;&#xb5;g/kg, MG), butorphanol group (50&#xa0;&#xb5;g/kg, BG), or medetomidine-butorphanol group (10&#xa0;&#xb5;g/kg&#x2009;+&#x2009;50&#xa0;&#xb5;g/kg, MBG). Butorphanol was administered 5&#xa0;min after medetomidine in the MBG. M-mode echocardiography was performed from a right parasternal short-axis view at baseline and at 5, 15, 30, 45, 60, 90, and 120&#xa0;min after treatment. Left ventricular internal diameter (LVID), interventricular septal thickness (IVST), and left ventricular posterior wall thickness (LVPW) were measured at end-diastole (d) and end-systole (s). Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV), ejection fraction (EF%), and fractional shortening (FS%) were calculated. Data were analyzed using a repeated-measures general linear model. Medetomidine alone was associated with significant reductions in EF% and FS%, together with significant changes in LVIDs and LVIDd. SV was also significantly lower in the medetomidine group than in the control group during the main post-treatment period; however, SV and the calculated LV volumes were interpreted cautiously because they are load-dependent variables derived from linear M-mode measurements. These changes were accompanied by an increase in LVIDs and a reduction in IVSs, indicating transient depression of conventional left ventricular systolic indices and altered loading conditions. Butorphanol alone produced only minor, parameter-specific changes in LVID, IVST, and most echocardiographic indices, with no consistent clinically relevant deterioration compared with baseline or the CG. In contrast, the MBG showed marked changes in ventricular dimensions and calculated indices from 15 to 60&#xa0;min; however, these findings were interpreted cautiously because the calculated systolic indices are load-dependent. Intravenous medetomidine, butorphanol, and their combination exert distinct and protocol-dependent effects on left ventricular dimensions and systolic function in donkeys. Medetomidine alone substantially and transiently depresses systolic performance, whereas butorphanol alone is comparatively cardiovascular-sparing. The medetomidine-butorphanol combination may be considered for standing sedation in clinically healthy donkeys; however, its echocardiographic effects should be interpreted cautiously as load-dependent changes, and cardiovascular monitoring remains advisable.

This chapter summarizes the current knowledge on the practical, methodological, and interpretative aspects of applying metaproteomics in water biotechnology. We outline the full metaproteomic workflow-from sampling and protein extraction to LC-MS/MS acquisition, database construction, quantitative analysis, and bioinformatic interpretation-and emphasize critical considerations specific to complex matrices such as EPS-rich biofilms, granular sludge, and low-biomass drinking water. Case studies illustrate how metaproteomics can clarify mechanisms of micropollutant degradation, nitrogen-transforming pathways, biofilm functional architecture, and microbial resilience under operational stress. Recent advances in data-independent acquisition, metagenome-informed databases, and integrative multi-omics are shown to substantially improve depth, reproducibility, and functional resolution. Finally, we discuss emerging applications in wastewater-based epidemiology, where metaproteomics complement nucleic-acid-based surveillance by enabling the detection of large biomolecule biomarkers of population health and industrial activity. Although metaproteomics is already being applied across a wide range of water cycle contexts and is producing promising, robust results, several challenges, including limitations in analytical chemistry, database completeness, and bioinformatics workflows, continue to hinder its broader implementation. Continued technical research and innovation are therefore essential to fully unlock its potential in water biotechnology.

Our understanding of the influence of ancestral background on genetically determined expression remains limited, especially when gene expression models are applied to studies from different or multiple populations. We perform transcriptome-wide association studies of 6 psychiatric conditions, leveraging gene expression models trained in cohorts with different proportions of African, European, and Indigenous American genetic ancestries. For comparison, we repeat each transcriptome-wide association study using a model trained in individuals of predominantly European ancestry. We identify 1416 statistically significant gene-level associations (false discovery rate adjusted p&#x2009;<&#x2009;0.05) across the 6 diagnoses, of which 62% are uniquely detected by the admixed gene models. Notably, we observe high correlation (&#x3c1;>0.92) in the gene-level effects on disease risk across ancestries, a statistic that remains robust for results that only reach statistical significance in one population. The genes identified by the admixed models implicate more neurophysiological features (as measured by brain imaging) associated with diagnostic symptoms. Overall, admixed gene expression models greatly extend the yield of transcriptome-wide association studies and substantially enhance validation, enabling more precise mapping of genetic effects to underlying pathophysiological mechanisms and highlighting potential avenues for therapeutic development.

Hospital-acquired infections (HAIs) remain a major global concern, contributing significantly to increased morbidity, mortality, and healthcare costs. Among the causative pathogens, Escherichia coli (E. coli) is one of the most frequently isolated microorganisms, particularly in urinary tract infections (UTIs), bloodstream infections, and surgical site infections. Early and accurate prediction of E. coli infection in hospitalized patients remains a significant clinical challenge, yet it has the potential to substantially improve patient outcomes. In addition, identifying patient-related risk factors can support targeted infection control strategies. This study aims to evaluate a no-code machine learning (ML) approach for early prediction of E. coli infection and to identify associated risk factors. ML techniques provide a powerful alternative by enabling the analysis of high-dimensional and heterogeneous datasets, facilitating the discovery of hidden patterns and supporting individualized risk prediction. In this study, a total of 300 clinical samples was collected as a training dataset from hospitalized patients between July 2024 and February 2025 across multiple units of Zagazig University Hospital, Sharkia, Egypt. An independent internal validation dataset of 100 samples was collected during May 2026 from the same hospital, its purpose was to evaluate model generalizability on completely unseen data. Bacterial isolates were identified using standard biochemical methods. Data analysis was performed using the Orange visual programming platform, implementing a modular ML pipeline that integrates data preprocessing, feature handling, model training, and performance evaluation within a no-code environment. The Naive Bayes model, shows potential for predicting E. coli infection in hospitalized patients. The model is intended to predict E. coli infection at the time of specimen collection, before culture results are finalized, depending on clinical data. However, further validation in larger, multi-center prospective cohorts is needed before clinical implementation.

Pathological scars are characterized by persistent fibroblast activation and excessive extracellular matrix (ECM) deposition. Although oxidative stress and dysregulated NRF2 signaling contribute to TGF-&#x3b2;1-mediated fibrosis in internal organs, their roles in cutaneous pathological scarring remain unclear. Secretome-based cell-free therapies have shown regenerative and antifibrotic potential, but whether lipoaspirate-derived secretome can restore fibroblast redox homeostasis and thereby attenuate pathological scarring is unknown. Lipoaspirate fluid obtained during standard tumescent liposuction was processed by 100-kDa ultrafiltration to generate lipoaspirate-derived secretome (LA), while secretome from adipose-derived stromal cell (ADSC) culture supernatant served as a comparator (CS). LA and CS were characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting for EV markers. In vivo efficacy was evaluated in a rabbit ear scar model with weekly intradermal LA injection, followed by gross, histological, collagen, and qPCR assessments. Comparative proteomic profiling of LA and CS was performed using data-independent acquisition LC-MS/MS with enrichment analysis, and paired human scar and normal skin samples were analyzed by single-cell RNA sequencing. In vitro, TGF-&#x3b2;1-stimulated fibroblasts were treated with LA or CS, and NRF2 involvement was assessed using the inhibitor ML385 or Nrf2-targeting siRNA. Redox balance, NRF2 signaling, and profibrotic responses were assessed by fluorometric assays, qPCR, and immunoblotting. LA showed a substantially higher particle yield than CS and contained abundant extracellular vesicles. Weekly intradermal LA injections reduced scar formation and improved collagen organization in the rabbit ear model. Comparative proteomics of LA versus CS highlighted cytoprotective pathways, including glutathione metabolism and NRF2-associated antioxidant signaling. Analyses of human scar tissues revealed elevated NOX4 expression, increased 4-HNE, and impaired NRF2-associated antioxidant signaling in scar fibroblasts. In vitro, both LA and CS attenuated TGF-&#x3b2;1-driven profibrotic fibroblast activation, whereas LA showed greater antioxidant activity, including stronger suppression of oxidative stress-related responses and improved GSH/GSSG balance. Pharmacological inhibition and genetic silencing of NRF2 partially reversed the antioxidant and antifibrotic effects of LA. Lipoaspirate-derived secretome (LA) is a clinically accessible cell-free therapeutic candidate for pathological scarring. LA restores redox homeostasis, in part through NRF2-associated antioxidant signaling, attenuates TGF-&#x3b2;1-driven profibrotic fibroblast activation, and improves scar remodeling in vivo. These findings support LA as a promising cell-free strategy for attenuating pathological scar formation.

Precise quantification of the causative agent of syphilis, Treponema pallidum (T. pallidum) is critical for advancing research in pathogenesis, treatment response, and vaccine development. However, current methods have certain limitations. Dark-field microscopy (DFM) suffers from low sensitivity, poor reproducibility, and strong operator dependence, while quantitative PCR (qPCR) offers high precision but is time-consuming, technically demanding, and reliant on high-quality, consistent commercial reagents. This methodological bottleneck highlights the urgent need for a technique that integrates the speed and simplicity of direct detection with the precision, objectivity, and throughput of an automated assay. Herein, to bridge this gap, we propose a strategy for rapid, high-throughput quantification of T. pallidum using a novel, fluorescence-based flow cytometric assay implemented on an automated urine analyzer (the Sysmex UF-5000 analyzer). The assay demonstrated a limit of detection of 7.02&#x2009;&#xd7;&#x2009;10&#xb3;T. pallidum/mL and excellent precision (all coefficients of variation&#x2009;<&#x2009;20%). It showed strong quantitative agreement with qPCR across a wide dynamic range (4.98&#x2009;&#xd7;&#x2009;103-2.10&#x2009;&#xd7;&#x2009;107T. pallidum/mL), with an excellent correlation (r&#x2009;=&#x2009;0.9967), without significant proportional or constant bias (Passing-Bablok slope&#x2009;=&#x2009;1.003). Bland-Altman analysis confirmed a close agreement (mean difference: -1.14&#x2009;&#xd7;&#x2009;105T.pallidum/mL). In contrast, DFM exhibited substantially higher variability (CVs 15.19-83.52%) and failed to detect low-concentration samples. Operationally, the flow cytometric assay provides results within 30&#xa0;s per sample at a low consumable cost (approximately $0.35 per test), outperforming DFM in objectivity and throughput and qPCR in both speed and cost-effectiveness. In summary, this novel flow cytometric assay effectively overcomes the historical challenges associated with T.pallidum quantification. This automated, precise, and rapid assay integrates the simplicity of direct detection with the accuracy of molecular quantification, offering a standardized and practical tool to enhance research in syphilis microbiology, pharmacology, and immunology, paving the way for more reproducible and translatable scientific discoveries.

Semilocal density functionals such as the Perdew-Burke-Ernzerhof (PBE) functional substantially underestimate experimental band gaps. Hybrid functionals address this band gap problem by admixing a fraction of Fock exchange to semilocal exchange. The optimal mixing parameter depends on the specific material and can be identified as the inverse dielectric constant (dielectric-dependent hybrid functional, DDH). Here, we show that dielectric constants obtained using the r2SCAN meta-GGA functional are significantly more accurate than dielectric constants obtained using the semilocal PBE functional. We propose the DD-r2SCANH functional, a dielectric-dependent hybrid functional based on r2SCAN. DD-r2SCANH can outperform the standard PBE-based DDH in terms of band gaps and other electronic structure properties. Particularly marked improvements are obtained for narrow-gap semiconductors such as Ge and InAs, where PBE wrongly predicts a metallic phase, but r2SCAN opens a band gap.

The remediation of cadmium (Cd)-contaminated agricultural soils poses great challenges. Electrokinetic technology can effectively remediate Cd-contaminated soils, but the electrode polarization effect restricts its remediation efficiency. Therefore, in this study, Cd-contaminated paddy soil samples from northern Guangxi were used as the research object. An L&#x2089;(3&#x2074;) orthogonal experimental design was employed to investigate the effects of power supply duration, voltage gradient, power supply mode, and electrolyte type on the remediation efficiency of Cd-contaminated soil via electrogeochemical survey technology, and to determine the optimal electrokinetic remediation parameters. The results indicate that the optimal electrokinetic remediation parameters were a voltage gradient of 0.6&#xa0;V/cm, a duration of 144&#xa0;h, continuous power supply, and EDTA-2Na as the electrolyte. Among all experimental runs, the highest measured removal efficiency (49.14%) was achieved in the EK6 group. Statistical analysis revealed that the priority of influence of each factor is electrolyte type&#x2009;>&#x2009;voltage gradient&#x2009;>&#x2009;power supply duration, whereas the effect of the power supply mode was not significant. Mechanistic analysis reveals that EDTA-2Na forms EDTA4- at the cathode, which coordinates with Cd2+ to generate the stable [Cd-EDTA]2- complex. This process effectively mobilizes the recalcitrant Cd fractions, and increases the proportion of the water-soluble fraction of Cd in soil from less than 0.1% to over 35%. Concurrently, the electrogeochemical survey configuration suppressed electrode polarization, and no white film deposition was observed on any of the electrodes. These combined effects resulted in an average Cd removal efficiency of 46.6% with EDTA-2Na, substantially outperforming both citric acid (39.4%) and double deionized water (41.2%). The combined application of electrogeochemical survey with EDTA-2Na forms a synergistic multiphase electrochemical reaction mechanism, significantly improving the overall remediation efficiency of Cd-contaminated soil.

Food market accessibility is a critical yet underexplored dimension of food systems, particularly in low- and middle-income countries. In this paper, we present a continent-wide assessment of spatial food market accessibility in Africa, integrating open geospatial data from OpenStreetMap and the World Food Programme. We compare three complementary metrics: travel time to the nearest market, market availability within a 30-minute threshold, and an entropy-based measure of spatial distribution, to quantify accessibility across diverse settings. We find pronounced disparities in accessibility: rural and economically disadvantaged populations face substantially longer travel times and reduced market availability, with some areas requiring several hours of travel. These accessibility patterns align with socioeconomic stratification, as measured by the Relative Wealth Index, and moderately correlate with food insecurity levels, assessed using the Integrated Food Security Phase Classification. Overall, results suggest that access to food markets reflects broader geographic and economic inequalities and plays a relevant role in shaping food security outcomes. Despite limitations related to incomplete and spatially heterogeneous market data coverage, this framework provides a scalable, data-driven approach for identifying relative structural market accessibility gaps, supporting equitable infrastructure planning and spatially informed food security analyses across diverse African contexts.

Postoperative stroke can undermine the benefits of endovascular stenting for cerebrovascular stenosis. This trial investigated whether adjunctive remote ischemic conditioning (RIC) improves cerebral blood flow (CBF) regulation and reduces the risk of postoperative stroke. A total of 104 patients with intracranial or extracranial cerebrovascular stenosis who underwent endovascular stenting were enrolled and randomized to receive either RIC or sham-RIC (1:1). The intervention was administered twice daily for 7 consecutive days postoperatively. CBF regulation was assessed bilaterally using transfer function analysis of spontaneous blood pressure and CBF oscillations at baseline and on day 7 or at discharge. The primary outcomes were phase difference (PD) and gain, whereas the secondary outcomes were 90-day stroke incidence and safety. Significantly higher PD values were observed in the RIC group than in the sham-RIC group on the affected side (40.67&#xb0; [26.76&#xb0;-58.28&#xb0;] vs. 20.51&#xb0; [10.90&#xb0;-41.73&#xb0;], P&#x2009;<&#x2009;0.001) and the unaffected side (36.04&#xb0; [21.66&#xb0;-54.53&#xb0;] vs. 26.80&#xb0; [11.94&#xb0;-44.83&#xb0;], P&#x2009;=&#x2009;0.022), indicating improved CBF regulation. Intragroup comparisons revealed significant PD improvement from baseline to day 7 or discharge in the RIC group (affected side: 20.57&#xb0; [8.70&#xb0;-34.24&#xb0;] vs. 40.67&#xb0; [26.76&#xb0;-58.28&#xb0;], P&#x2009;<&#x2009;0.001; unaffected side: 26.06&#xb0; [8.70&#xb0;-44.37&#xb0;] vs. 36.04&#xb0; [27.66&#xb0;-54.53&#xb0;], P&#x2009;=&#x2009;0.001). The 90-day stroke incidence was significantly lower in the RIC group (0.00% vs. 9.62%, P&#x2009;=&#x2009;0.022). Adjunctive RIC safely enhanced CBF regulation and substantially reduced postoperative stroke in patients after cerebrovascular stenting, suggesting a promising non-pharmacological strategy to improve outcomes. This trial was registered at ClinicalTrials.gov (NCT05970653).

The roles of Contactin-2 (CNTN2) and ferroptosis in heart failure and cardiac remodeling remain incompletely understood. CNTN2 was significantly upregulated in hypertrophic cardiomyopathy patients and heart failure mice. In cardiomyocyte specific CNTN2 conditional knockout (CNTN2 cKO) mice, transverse aortic constriction (TAC) induced markedly exacerbated heart failure, cardiac remodeling and ferroptosis compared to control mice. Ferroptosis inhibition substantially attenuated heart failure in CNTN2 cKO mice subjected to TAC, indicating that enhanced ferroptosis contributes to the detrimental effects of CNTN2 deficiency. RNA sequencing identified NUPR1, a ferroptosis repressor, as a downstream molecule of CNTN2. Mechanistically, CNTN2 activated the Lyn/eIF2&#x3b1;/ATF4 pathway to regulate NUPR1. CNTN2 overexpression attenuated Angiotensin II-induced cardiomyocyte ferroptosis and pathological remodeling, whereas these protective effects were abolished by Lyn or NUPR1 inhibitors. We further revealed CNTN2 and Lyn interacted with each other, and that CNTN2 interacted with Lyn through its 1-328aa domain. In vivo NUPR1 overexpression via AAV9 significantly mitigated TAC-induced heart failure and cardiac remodeling in CNTN2 cKO mice. Our study demonstrates that CNTN2 protects against pressure overload induced heart failure and cardiac remodeling by regulating ferroptosis through the Lyn/eIF2&#x3b1;/ATF4/NUPR1 pathway, suggesting CNTN2 as a potential therapeutic target.

Species elevational shifts are well-documented responses to climate change, with many moving upslope to track suitable conditions. However, these shifts can vary considerably in both direction and rate, and the underlying causes of this variability are not well understood. This study examines how elevational shifts depend on geographical zones along with species' climatic niches, global prevalence, and evolutionary history by analyzing paired lower and upper edge shifts across 845 plant and animal species records worldwide. We find distinct effects of these drivers on upper versus lower distribution limits. Tropical species experienced more rapid upward shifts of their lower edges than did temperate species. Species with warmer and wetter optimal climatic niches displayed faster upper-edge shifts, while those only with wetter ones showed more rapid lower-edge shifts. Globally prevalent species expanded their distributions with climate change by combining faster upper-edge advances with slower lower-edge contractions, likely reflecting their drier climatic adaptation. Importantly, these ecological effects overlapped substantially with phylogenetic effects, and phylogenetic conservatism independently explained a notable portion of the variation in elevational responses. These findings highlight the complexity of evolutionary history and ecological processes in shaping species' climate responses and underscore the climate vulnerability of some species due to their evolutionary inertia.