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By using the naphthalene group-containing β-diketone ligand and 5-nitro-1,10-phenanthroline, three novel heteroleptic eight-coordinate complexes of Eu(III), Tb(III), and Gd(III) have been synthesized. Methods such as elemental analysis, MALDI TOF-MS, UV-Vis, and FT-IR were used to determine the structural characterization of these compounds. The photoluminescent characteristics of the synthesized complexes of Eu(III), Tb(III), and Gd(III) were further investigated. The ligand (L1) and co-ligand 5-nitro-1,10-phenanthroline (L2) and its three lanthanide complexes [Eu(L1)3(L2)]·3H2O, [Tb(L1)3(L2)], and [Gd(L1)3(L2)] were tested in human breast (MCF-7), colon (DLD-1), and lung (A549) cancer cell lines for 72 h. Furthermore, these compounds were screened in a human embryonic kidney cell line (HEK-293T) for cytotoxicity. The results demonstrated that these compounds have antiproliferative activity in three cancer cell lines with low IC50 values. The probable mode of action for the cytotoxic effect was explored through molecular modeling. Previous studies reported epidermal growth factor receptor (EGFR)-inhibiting potential for compounds with similar scaffolds. The docking study demonstrated that the three chelates would have the potential to bind to the EGFR structure. The molecular dynamics (MD) simulation study consolidated this finding as the complex structures were found to be stable with some differences. MMPBSA (molecular mechanics with Poisson-Boltzmann and surface area solvation) energy calculation results also showed high binding affinities for the chelates.

Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. Twelve metabolic, behavioral, and environmental risk factors. The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

Diffuse large B-cell lymphoma (DLBCL) frequently relapses following therapy, partly due to microenvironment-mediated drug resistance. Bone marrow involvement is associated with poor prognosis, yet preclinical models that faithfully recapitulate its extracellular matrix (ECM) remain limited. We used a decellularized human bone-derived 3D scaffold to evaluate the impact of extracellular matrix (ECM) interactions on proliferation, cytokine secretion, and ibrutinib sensitivity in four DLBCL cell lines (OCI-LY1, OCI-LY18, RIVA, NU-DUL-1). Functional assays and cytokine profiling were performed under 2D and 3D culture conditions. Compared with 2D cultures, the 3D ECM model induced a profound remodeling of the DLBCL secretome, with upregulation of a coordinated network of pro-migratory chemokines, particularly CXCL9, CCL22, CCL17, CCL4 and CXCL1/2/3. ECM engagement enhanced DLBCL migration and promoted scaffold colonization, indicating a positive feedback loop between tumor cells and the microenvironment. While all DLBCL cell lines were sensitive to ibrutinib in 2D, ECM-adherent OCI-LY18 and RIVA cells showed reduced drug-induced apoptosis in 3D. This effect was dependent on direct ECM contact, was not reproduced by inert 3D scaffold, and was fully reversible upon disruption of cell-ECM interaction. Mechanistically, ECM adhesion was associated with activation of the AKT/mTOR pathway. The human bone-derived 3D ECM model reveals that direct tumor-matrix interactions induce reversible ibrutinib resistance and reshape the cytokine milieu in DLBCL. These findings highlight the role of ECM as a dynamic regulator of drug response and support the use of physiologically relevant 3D models to investigate microenvironment-driven resistance and guide therapeutic strategies.

The rise of multidrug-resistant microbes, rapidly evolving viruses, and recurring pandemics underscores the urgent need for advanced vaccine technologies. Nanoparticle-based vaccines have emerged as a transformative approach capable of overcoming the major shortcomings of traditional immunization methods. Their nanoscale architecture allows precise antigen targeting, enhanced stability, and controlled release, leading to more potent and durable immune protection. These smart systems can carry multiple antigens or adjuvants, mimic natural pathogens, and efficiently activate immune cells to elicit strong humoral and cellular responses. Various nanoparticle types, lipid-based, polymeric, inorganic, and biomimetic, demonstrate broad potential against infectious, inflammatory, and neoplastic diseases in both humans and animals. However, critical barriers remain in mass production, regulatory harmonization, and long-term safety assurance. The integration of nanotechnology with artificial intelligence (AI) and bioengineering now enables rational vaccine design, predictive modeling, and personalized immunization strategies. AI-driven optimization of nanoparticle formulations and immune response prediction are accelerating translational progress. The convergence of these disciplines is shaping a new generation of vaccines that are safer, more effective, and adaptable to global health challenges, paving the way toward precision vaccination for the modern era.

Reviewing pathology, imaging, and consultation documents in oncology can be time-consuming, particularly when records originate from external facilities in different file formats. This study aimed to evaluate the impact of a Retrieval-Augmented Generation (RAG)-enabled GPT-4o summarization agent on clinical workflows and quality of outside-record summaries in breast surgical oncology. Initial performance evaluation of a GPT-4o/RAG agent to generate summaries of oncologic reports in 50 charts followed by a prospective pilot test of sequential cases, with each AI summary evaluated using a modified Provider Documentation Summarization Quality Instrument (PDSQI-9; 1-5 Likert scale), including dichotomized ratings (low [1-3], high [4, 5]), binomial testing, frequency and type of user-reported errors, clinician-coded error criticality (treatment-impacting vs noncritical). Pre- and post-use survey of documentation burden (NASA TLX) and user experience was performed. Among 62 cases, AI-generated summaries were rated high for accuracy, usefulness, succinctness, and source citation. Thoroughness without omission was rated low in 28 (45%) summaries. Errors were noted in 25 (40%) surveys, with 13 (52%) classified as critical (treatment-impacting). The most common error type involved imaging, reported in 17 (68%) cases. For perceived time savings, the median response was neutral, but qualitative feedback described the tool as helpful for straightforward cases and as reducing typing burden but requiring workflow adjustment and improvements for complex cases. Although users rated RAG-enabled GPT-4o agent-generated documentation summaries favorably on several quality domains, they frequently lacked thoroughness and occasionally contained treatment-relevant errors. Human review and further iteration of the technology remain necessary before implementation.

The impact of metals on atherosclerotic cardiovascular disease (ASCVD) risk in workers occupationally exposed to welding fume remains unclear. We aimed to assess the associations between welding-related metals and 10-year ASCVD risk, and the mediating role of biological aging. Metals including chromium, manganese, nickel, lead, copper (Cu), and iron were detected and biological aging indices, including Klemera-Doubal method biological age (KDM-BA) and Phenotypic Age (PhenoAge), were calculated among 419 male welders in Wuhan, China. The participants had an average age of 42.77 years, of whom 93 (22.2%) fell into the high 10-year ASCVD risk group. Generalized linear models revealed that Cu was associated with elevated 10-year ASCVD risk [OR (95% CI) = 1.051 (1.017, 1.085), P = 0.003]. This association persisted even after adjustment for other metals. Moreover, we found positive associations between biological aging and 10-year ASCVD risk [KDM.Accel: OR (95%CI) = 1.170 (1.070-1.280); PhenoAge.Accel: OR (95% CI) = 1.122 (1.053-1.194)], as well as between Cu and biological aging [KDM.Accel: β (95% CI) = 1.888 (1.130-2.646); PhenoAge.Accel: β (95% CI) = 4.552 (3.406-5.698)]. Further analysis showed significant mediation roles of KDM.Accel and PhenoAge.Accel in the Cu-ASCVD association, with mediating proportions of 29.8% and 43.8%, respectively. We further constructed a lifestyle index, suggesting that a modifiable healthy lifestyle could decelerate aging and reduce the 10-year ASCVD risk. Our findings indicated that Cu was associated with increased ASCVD risk, and biological aging may mediate the Cu-ASCVD association. Adopting healthy lifestyles appears to mitigate biological aging, which is of great public health importance for preventing ASCVD.

This study compares current Medicaid rebates with international reference prices and estimated potential savings under the Generating Cost Reductions for US Medicaid payment model.

Severe cutaneous toxic effects from chemotherapy and radiation often require treatment interruptions. High-dose oral vitamin D (hdVD) has shown potential as a rapid immunomodulator in experimental models and small human studies, but robust clinical data in oncology populations remain limited. To evaluate the clinical response, safety profile, and time to improvement for hdVD in patients with toxic erythema of chemotherapy (TEC) and acute radiation dermatitis (ARD). This retrospective multicenter case series included 33 patients treated across 3 academic medical centers between December 2021 and January 2024. Eligible participants were those receiving hdVD (100 000 international units) for TEC or ARD with at least 10 days of follow-up. One or 2 oral doses of 100 000 international units of cholecalciferol or ergocalciferol. The primary outcomes were time to patient-reported symptomatic relief and clinician-assessed objective improvement in erythema (using a 5-point Likert scale). Secondary outcomes included changes in serum calcium and the ability to continue anticancer therapy. Among 33 patients (mean [SD] age, 60.9 [14.6] years; 19 [58%] female), 28 (85%) had TEC and 5 (15%) had ARD. Subjective symptom relief was reported by 26 of 30 patients (87%) within 10 days of treatment. The median (range) time to improvement was 5 (1-28) days overall and 3 (1-16) days for the inpatient subgroup. The mean (SD) Likert erythema score decreased from 4.36 (0.60) at baseline to 2.21 (1.36) by day 10. Patients with neutrophilic eccrine hidradenitis and Stevens-Johnson syndrome/toxic epidermal necrolysis-like subtypes showed the most rapid responses. No meaningful changes in serum calcium levels were observed, and 24 of the 33 patients (73%) continued anticancer therapy without interruption. No treatment-related adverse events were reported during the study. In this case series, hdVD was associated with rapid symptomatic and objective improvement in chemotherapy- and radiation-induced toxic effects of the skin without treatment-related adverse events. These findings support further study of hdVD as a supportive care approach in oncodermatology.

Sedentary behavior poses significant risks to older adults yet remains an understudied health risk behavior. Studies typically overlook the importance of subject-level variability in psychological constructs as predictors of sedentary behavior, instead focusing on the role that typical or mean levels of these constructs play in predicting behavior. This study uses ecological momentary assessment and device-based sedentary behavior to determine the role of subject-level variability in psychological constructs as predictors of sedentary behavior in older adults. Findings reveal that subject-level variability in positive affect, but not motivational or self-regulatory constructs, is associated with sedentary behavior (total sedentary behavior: β = -18.136, SE = 8.284, p = .029; bouted sedentary behavior: β = -16.534, SE = 7.814, p = .034). The association between subject-level variability and total sedentary behavior tended to be positive but marginally significant among participants with lower mean levels of positive affect but was negative and significantly different from zero among participants with higher mean levels of positive affect. These findings highlight the importance of considering not only mean levels but also within-person fluctuations in psychological constructs as key predictors of sedentary behavior. Studies of this kind can inform the development of personalized interventions, tailored to patterns of determinants in key constructs.

The degradation of water quality, one of the major global environmental challenges, demands advanced and intelligent monitoring and prediction systems. This study uses data from the Rohri Canal in the Pakistani city of SBA to develop a combined IoT-based advanced deep learning (DL) model that can accurately forecast the water quality index (WQI) and water quality class (WQC). The sensors that are used under IoT are turbidity, temperature, pH, and total dissolved solids (TDS) to measure real-time parameters of water quality. All the acquired data are preprocessed with the help of a quality-aware fuzzy min-max neural network (QAFMMN) to reduce noise efficiently and increase the quality of the data. A combination of the addax optimization algorithm and the Nadam optimizer (AOA-NO) is used to select features, keeping only the most important ones, which makes the method computationally efficient. In this regard, the model known as the Swin-Transformer-depthwise separable convolutional neural network, trained with the circulatory system-based optimization method (ST-DSCNN-CSBO), is established. Indeed, one can see the incredible results of the proposed experimental research because the R2 score obtained therein equals 0.999, the mean absolute error (MAE) equals 0.008, and the overall water quality classification accuracy is equal to 99.96%.

Wound repair is an essential biological process that occurs both in tissues and single cells. In free-living single-celled ciliates such as Stentor coeruleus, rapid repair from wounds is necessary to heal breaches to the plasma membrane, where any delays represent the difference between life and death. In order to discover novel molecular pathways that are important for healing in Stentor, we carried out a targeted RNA interference-based perturbation genetic screen combined with microsurgical wounding using a microfluidic guillotine to introduce reproducible bisection wounds. We identified a Stentor syntaxin gene that was necessary for cell survival, particularly post-wounding, with only ∼37% of syntaxin-deficient cells surviving compared with ∼98% of control cells. Syntaxin-deficient cells were more susceptible to hypoosmotic shock and became increasingly vacuolated in the hours post-wounding, eventually leading to cell death. Wounding of the cells in 75 mM sorbitol during and after bisection partially restored the post-wound survival in knockdown cells. These results support the interpretation that syntaxin-deficient cells lack essential membrane fusion machinery, which manifests in vacuolar defects, and are deficient in maintaining osmotic homeostasis necessary for their survival post-wounding. This study provides a template for the discovery of new wound healing biology in emerging model systems.

In metazoans, gametogenesis produces the only cell type capable of transmitting both genetic and epigenetic information to offspring. This process represents one of the most extensive cellular differentiation programs, often originating from germline stem cells (GSCs), as in the female and male Drosophila and C. elegans gonads. These well-defined, unipotent germline lineages provide powerful in vivo models to study epigenetic regulation in multicellular organisms. During gametogenesis, epigenetic mechanisms balance cell differentiation and cellular plasticity. This review summarizes recent findings on how asymmetric sister chromatids are established and segregated during GSC division, the initial step of gametogenesis essential for reproduction in Drosophila and C. elegans. We focus on histones, a major carrier of epigenetic information, and discuss how their inheritance is regulated during GSC asymmetric divisions. Canonical histones and histone variants are dynamically incorporated into chromatin in a cell cycle- and genomic locus-specific manner, and these chromosome-bound epigenetic differences must coordinate with the mitotic machinery to ensure their proper partitioning. Finally, we speculate how these mechanisms may extend beyond the germline, assessing their conservation across species. Understanding these processes provides critical insights into how misregulation contributes to disease and how targeted manipulation could promote tissue homeostasis and regeneration.

Family visits with nursing home residents have been shown to improve residents' quality of life. However, little is known about the association between in-person family visits and physical (e.g., pain) and behavioral symptoms (e.g., agitation) among residents with cognitive impairment. Using data from a large clinical trial of a palliative care program in Maryland and Indiana, we examined the association between family visits and staff-reported resident symptom burden. Using cross-sectional baseline data from an ongoing multi-state clinical trial involving 194 nursing home residents with cognitive impairment, we conducted bivariate analyses to examine the association between in-person family visits (family involvement) as reported by family members and staff-reported resident symptom burden. Linear regression models assessed the association between symptom burden and family visits in an adjusted framework. The model controlled for other relevant covariates, including resident race, gender, and age, and the care partner's relationship to the resident. Staff-reported symptom burden was measured using a modified version of the Comfort Assessment in Dying End of Life in Dementia (CAD-EOLD) scale. Family involvement was measured by the average weekly frequency of in-person visits reported by the family over the past month. On average, spouses visited 5 days per week, children 2 days per week, and other family members 1.5 days a week. In bivariate analyses, there was a weak but statistically significant and positive correlation between family involvement and symptom burden (r = 0.16, p = 0.04). However, in the adjusted model, the association was not statistically significant (b = 0.16, p = 0.09). Bivariate analyses suggest a significant and positive correlation between family visitation and symptom burden. However, this finding was not in the expected direction. Family visitation was associated with residents experiencing greater symptom burden. The association was not statistically significant in the adjusted model. ClinicalTrials.gov identifier: NCT04520698.

Childhood cancer is a leading cause of disease-related mortality, with increasing incidence in many high-income countries. Socioeconomic disparities in childhood cancer survival are well documented, but less is known about incidence. To examine associations between area-based deprivation and childhood cancer incidence in a universal health care system. This population-based cross-sectional study linked data from the population-based Pediatric Oncology Group of Ontario Networked Information System cancer registry with Statistics Canada's postal code and Ontario Marginalization Index (ON-Marg) databases to identify pediatric cancer cases diagnosed in Ontario from January 1, 1999, to December 31, 2023, among approximately 2.3 million children aged 0 to 14 years living in Ontario, Canada. Data analysis was performed from October 2025 to February 2026. ON-Marg dimensions: material resources (income and educational attainment), households and dwellings (residential instability), age and labor force (dependents and adults not in the labor force), and racialized and newcomer populations. Crude and age-standardized incidence rates for each ON-Marg dimension; incidence rate ratios were estimated using multivariable Poisson regression models adjusted for age, sex, and diagnosis period for the overall population and stratified by cancer subtype (ie, leukemia and lymphoma, central nervous system tumors, and other non-central nervous system solid tumors). Of the 9063 pediatric cancer cases (4981 [55.0%] male; median [IQR] age at diagnosis, 5 [2-10] years), the age-standardized incidence rate was 162.7 cases per million (95% CI, 159.3-166.1). Most cancer cases were found in areas with the greatest concentration of racialized and newcomer populations; however, after accounting for population size, there was no difference in cancer incidence across quintiles. A key finding of this study was that the least marginalized quintiles of material resources (incidence rate ratio, 1.15; 95% CI, 1.07-1.22) and households and dwellings (incidence rate ratio, 1.08; 95% CI, 1.01-1.16) had significantly higher incidence rates compared with the most marginalized quintiles. These findings were driven primarily by hematologic and other solid cancer types. This large population-based cross-sectional study with virtually complete ascertainment of pediatric cancer cases in a Canadian province with a universal health care system found higher cancer incidence among children who lived in affluent and residentially stable neighborhoods. These findings underscore the importance of considering sociodemographic factors when examining pediatric cancer epidemiology; more research is needed to understand the mechanisms driving these differences, their impact on outcomes, and how the findings may inform targeted prevention and intervention strategies.

Antiretroviral therapy (ART) interruptions are common among people who inject drugs (PWID) and contribute to viral rebound, disease progression, and onward transmission. Data-to-Care (D2C) strategies, which use routine health data to identify and re-engage people living with HIV who have fallen out of care, are widely used in high-income settings but rarely evaluated in low- and middle-income countries. We piloted a Ukrainian Data-to-Care (UD2C) intervention integrated into the national HIV Medical Information System among HIV-positive PWID recently out of care. Four specialized HIV clinics were randomized to UD2C or care as usual (CAU), with 40 participants enrolled per clinic (n = 160). UD2C combined an optimized data query to identify out-of-care patients with multidisciplinary, acuity-based case management. Recruitment, data extraction, and intervention delivery were feasible across all clinics. Because recruitment required clinic attendance, the pilot assessed UD2C's post-linkage care component rather than its re-engagement function. The primary analysis accounted for clinic-level clustering using cluster-robust standard errors. Median ART coverage during follow-up was higher in UD2C than CAU (97% vs. 89%; adjusted rate ratio 1.15, 95% CI 0.87-1.51); this difference was significant in the model-based sensitivity analysis but not in the primary clustered analysis. Viral suppression was achieved or maintained more often in UD2C than CAU (58.8% vs. 28.8%; adjusted odds ratio 4.6, 95% CI 1.76-12.1). The UD2C model was feasible to implement and evaluate using a cluster-randomized design and showed promising improvements in longitudinal viral suppression. A fully powered definitive trial is warranted to confirm effectiveness and inform national scale-up. The trial is registered at www.clinicaltrials.gov as NCT05821413.

To prospectively evaluate audiologic outcomes in patients with thyroid eye disease (TED) treated with teprotumumab, focusing on longitudinal changes in hearing sensitivity and cochlear function. Adult patients initiating teprotumumab therapy at a tertiary care center (2023-2025) underwent audiologic evaluations before, during, and after treatment. Pure-tone audiometry (500-12,500&#xa0;Hz) and distortion product otoacoustic emissions (DPOAEs; 842-7996&#xa0;Hz) were analyzed using three-level mixed-effects models to assess longitudinal changes, with secondary analyses controlling for baseline hearing loss. Sixteen participants completed the study. Significant threshold elevations suggesting reduced hearing sensitivity were observed in 6 of 9 audiometric frequencies (p&#x2009;<&#x2009;0.05), most prominent during active therapy. Partial recovery occurred post-treatment, though thresholds rarely returned to baseline. DPOAE analyses showed fewer consistent changes, with significant amplitude reductions at only 4 of 24 frequencies. Adjusting for baseline hearing loss reduced significance for isolated measures but not overall trends. As multiple comparisons were not formally adjusted for, these findings should be interpreted as exploratory and hypothesis-generating. Teprotumumab therapy appears to be associated with sensorineural hearing decline detected by audiometry but incompletely captured by DPOAEs. This mismatch suggests injury beyond outer hair cells, possibly involving inner hair cells or neural elements. These findings may support audiometric monitoring during treatment and further research into teprotumumab's ototoxic mechanisms during treatment of TED.

Biologic agents are commonly used with conventional immunosuppressants for treatment of immune-mediated dermatologic diseases, raising concerns about tuberculosis (TB) risk, particularly in high-burden geographic regions. Previous studies have shown inconsistent results across biologic classes, with most focusing on active TB and limited data on latent TB infection (LTBI) conversion. To evaluate the incidence of active TB and LTBI conversion in dermatologic patients receiving systemic therapy and to explore differences by biologic class and regional TB burden. PubMed/MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Library were searched from database inception to October 1, 2025. Controlled vocabulary and free-text terms were used for dermatologic diseases, systemic therapies, and tuberculosis-related outcomes. Clinical trial registries and reference lists were also screened. Randomized clinical trials, cohort studies, case-control studies, and cross-sectional studies reporting active TB or LTBI conversion in dermatologic patients receiving systemic therapy were included. Two reviewers independently screened records and performed full-text assessment. Data extraction and risk-of-bias assessment (Newcastle-Ottawa Scale and Cochrane Risk of Bias tool) were conducted independently by 2 reviewers following PRISMA guidelines. Single-arm incidence rates were pooled using random-effects models with logit transformation. Prespecified subgroup analyses were conducted by biologic class and regional TB burden. Primary outcomes were incidence of LTBI conversion (among patients with negative baseline results of tuberculin skin test or interferon-gamma release assay) and active TB during follow-up. Of 4726 records identified, 31 studies comprising a total of 15&#x202f;005 patients met inclusion criteria and were included in the analysis. The pooled incidence of LTBI conversion was 4.3%, highest with tumor necrosis factor inhibitors, followed by interleukin (IL)-17 and ustekinumab (IL-12/23 p40 inhibitor). The overall incidence of active TB was 1.0% and it was more frequent in high-burden regions. In this systematic review and meta-analysis, TB-related risk varied by biologic mechanism and epidemiologic context. Risk assessment and monitoring should integrate dermatologic treatment class and regional TB burden to guide clinical decision-making.

Urban rat populations are widely assumed to increase under climate change, largely due to recent studies. This narrative is often extended to cities worldwide, irrespective of their local climate. Yet, this oversimplification obscures complex ecological and social processes that shape commensal rat dynamics. Here, we synthesize evidence across rodent ecology, epidemiology, urbanization, and human behavior to propose a multi&#x2011;dimensional framework for urban rat&#x2011;release: a climate&#x2011;mediated relaxation of seasonal constraints that reduces winter burrow confinement and increases above&#x2011;ground activity, dispersal, apparency, and reproductive output in cold&#x2011;temperate cities, often producing short&#x2011;term population increases before density&#x2011;dependent processes stabilize numbers. Warming winters may extend breeding windows and increase winter food availability, but these effects interact with expanding arthropod vectors, shifting pathogen pressures, and the compounding forces of urban architecture, waste management systems, and human activity. Human social responses-sanitation reforms, surges in panic&#x2011;driven control, and predictable political attention cycles-can either magnify or suppress populations, often more strongly than ecological factors. We argue that climate change will not produce uniform increases in rat abundance; instead, outcomes will vary predictably across cold&#x2011;temperate, mild&#x2011;temperate, and tropical cities depending on the alignment of these interacting dimensions. Importantly, rat populations may stabilize or surge depending on how disease dynamics, density-dependent constraints, and public responses converge. This framework provides a foundation for forecasting models and offers practical guidance for urban planning, public health, and policy development in warming climates where rats and vectors reshape urban risks. These dynamics align with the One Health perspective, which emphasizes the interdependence of human, animal, and environmental systems.