ABSTRACT Background Climate change is intensifying public health risks and placing increasing pressure on disaster medicine systems. These challenges require adaptation strategies that incorporate climate justice principles and the One Health framework. Objective This scoping review aimed to examine how climate justice and One Health principles are incorporated into public health and disaster medicine adaptation policies. Methods A scoping review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta‐analyses extension for Scoping Reviews (PRISMA‐ScR) guideline using major scientific databases (Scopus, PubMed and Web of Science) and global health organization resources published between 01 January 2005 and 31 October 2025. Critical appraisal of included evidence was assessed using design‑specific tools: the JBI Critical Appraisal Checklist for systematic reviews and the Mixed Methods Appraisal Tool (MMAT) for mixed‑methods studies. Data were synthesized to assess the degree of public health engagement in climate adaptation and the incorporation of climate justice and One Health principles. Results Out of a total of 19,835 records, eight eligible studies were included. The eight studies comprised six review articles and two mixed‑methods studies, with geographic coverage, including Pakistan, the United States, Greece and multi‑country or global analyses. Findings reveal persistent inequities in climate‐related health impacts, particularly among marginalized and resource‐limited populations. Health sector participation in national adaptation plans remains limited, with policies often fragmented, mitigation‐oriented or insufficiently aligned with One Health principles. Structural inequalities, weak governance, gender disparities and limited multisector coordination hinder equitable adaptation. Climate stressors, including extreme weather events, air pollution, vector‐borne diseases and environmental degradation, disproportionately affect communities with the lowest adaptive capacity. Conclusions There is an urgent need for standardized vulnerability assessment frameworks, stronger multisector collaboration, improved early‐warning systems and enhanced capacity building through international public health institutions.
Abstract Background Despite optimal surgery, approximately 1 in 3 patients with renal cell carcinoma (RCC) will develop relapse. Adjuvant pembrolizumab has demonstrated a disease-free survival (DFS) and overall survival (OS) benefit in RCC, and recent data have also shown a DFS benefit with the addition of belzutifan to pembrolizumab. RAMPART (NCT03288532) is an investigator-led, international randomized phase III study, that enrolled patients with RCC at intermediate and high risk of relapse. Patients were randomized to observation (Arm A), durvalumab (Arm B), or durvalumab plus tremelimumab (Arm C). A significant DFS benefit was observed for Arm C compared to Arm A (DFS HR = 0.65, 95% CI 0.45 to 0.93, 1p = 0.009), but not for Arm B compared to Arm A (DFS HR = 0.74, 95% CI 0.53 to 1.04, 1p = 0.041). Given the toxicities associated with immunotherapy, biomarkers are needed to stratify patient risk and improve assignment to treatment. Kidney Injury Molecule-1 (KIM-1) has been identified as a prognostic marker post nephrectomy, though the mechanisms linking KIM-1 levels to risk are not fully established. Methods TransRAMPART prospectively collected longitudinal blood, tissue and urine samples alongside the main study, with the aim of identifying prognostic or predictive markers for adjuvant treatment. A total of 187 patients were recruited. Samples were collected at baseline, 16 weeks, 32 weeks, and at later timepoints up to 5 years. Plasma samples were profiled by MSD cytokine array including KIM-1, and peripheral blood mononuclear cells (PBMCs) were profiled by high resolution flow cytometry by IMU Biosciences. A baseline KIM-1 high threshold of ≥ 86pg/mL was applied, as used in the IMmotion010 study (Rini et al 2025). Survival analyses were performed using the Kaplan–Meier method, with log-rank p-values reported. Here we report the results for these exploratory blood-based analyses of Arms A, B and C. Results In the observation Arm A, patients with high baseline KIM-1 had significantly worse DFS compared to patients with low KIM-1 (HR 8.3, 95% CI 1.8 to 38, p = 0.0012, n = 45). This was not seen in either the durvalumab monotherapy group (HR 0.51, 95% CI 0.1 to 2.5, p = 0.41, n = 42) or in the combination group (HR 1.3, 95% CI 0.32 to 5.1, p = 0.72, n = 32). Within the KIM-1 high subgroup, durvalumab monotherapy was associated with significantly improved DFS compared to observation (HR 0.19, 95% CI 0.041–0.86, p = 0.016, n = 37), however no significant benefit was observed with combination therapy versus observation (HR 0.51, 95% CI 0.16–1.6, p = 0.25, n = 34). Among patients with low KIM-1, no significant differences in DFS were observed between durvalumab and observation (n = 49), nor between combination therapy and observation (n = 43). Patients with high KIM-1 had higher levels of baseline plasma CCL3 (p = 0.00248) and IL-12 (p = 0.0138). We were unable to detect any significant differences in PBMC profiles between patients with high and low KIM-1 levels. Conclusions As previously shown, elevated postoperative KIM-1 levels are prognostic in untreated patients. Although this exploratory analysis only assessed a subgroup of patients recruited to RAMPART, adjuvant therapy appears to attenuate the adverse prognostic effect of high KIM-1. High KIM-1 was predictive of benefit from durvalumab monotherapy. In contrast, no clear benefit from adjuvant therapy was observed in patients with low KIM-1. These findings support the hypothesis that KIM-1 may have predictive value for selecting patients for adjuvant therapy. Plasma cytokine profiles suggest increased baseline immune activity in patients with high KIM-1. Further work is needed to establish the relationship between KIM-1 status, immune activation states, and benefit from adjuvant immunotherapy.
Abstract Background Combination immune checkpoint inhibitor (ICI) approaches are now standard of care for advanced clear cell renal cell carcinoma (ccRCC), yet validated biomarkers to guide selection of optimal combination regimens remain lacking. A key rationale for combined PD-1/CTLA-4 inhibition is the subset of patients achieving durable responses. The tumour immune microenvironment (TiME) is increasingly recognised as a key determinant of this benefit, yet its cellular composition, functional state and spatial organisation, and how these evolve under dual ICI therapy, remain undefined. Methods Tumour specimens from 30 metastatic ccRCC patients across two independent cohorts (TRACERx Renal and the Netherlands Cancer Institute; NKI) were subject to longitudinal multi-modal profiling, all of whom underwent deferred cytoreductive nephrectomy following treatment with combined CTLA-4 (Ipilimumab) and PD-1 (Nivolumab) inhibition. Patients were classified as durable responders (DR; no documented progression event; median follow-up 40.8 months) or as having acquired resistance (AR; initial CR/PR/SD > 6 months prior to progression). Where available, matched pre-treatment biopsy material and multi-regional post-treatment surgical specimens underwent multi-modal spatial profiling (n = 116 tumour regions), co-registering high-plex protein imaging (66-plex antibody panel; Akoya PhenoCycler), with spatial transcriptomics (RNA in situ platform targeting 480 kidney tumour-specific genes; 10x Genomics Xenium) on the same tissue sections, enabling simultaneous protein and transcriptomic characterisation of the TiME at single-cell resolution. In a subset (n = 8; n = 28 tumour regions), single-cell RNA sequencing with paired TCR and BCR sequencing was performed to resolve treatment-induced clonotypic and phenotypic dynamics within T and B cell compartments. Results Dual ICI therapy induced consistent immune remodelling across the cohort irrespective of response, characterised by increases in B cells and CD8+ T cells and a reduction in monocytes/macrophages. At baseline, durable response was associated with increased pericyte coverage of tumour vasculature, whilst acquired resistance patients exhibited decreased pericyte coverage alongside elevated CD39 expression on tumour endothelial cells, implicating dysfunctional, immunosuppressive vasculature as an early determinant of resistance. Post-treatment, durable responders demonstrated enrichment of CCR7+ dendritic cell (DC) niches containing CD4+ T cells, CD8+ T cells and B cells across tumour and stromal compartments, alongside monocytes/macrophages and NK cells within tumour regions. By contrast, acquired resistance CCR7+ DC niches lacked specific immune cell enrichment, displayed dysregulated transcriptional programmes. Acquired resistance was further characterised by enrichment of TREM2+ immunosuppressive macrophages and peri-vascular spatial interactions between macrophages and CD4+ T cells, defining an immunosuppressive niche. scRNA-seq with paired TCR sequencing identified novel and shared memory/resident T-cell clonotypes enriched in durable responders, whilst clonally expanded IgG2 plasma cells were orthogonally validated by BCR sequencing and spatial profiling as a hallmark of durable response. Conclusions Using an integrated multi-omic spatial framework combining high-plex proteomics, single-cell and spatial transcriptomics, we provide a comprehensive characterisation of TiME remodelling under dual ICI therapy in ccRCC. Durable response is preceded at baseline by a normalised vascular phenotype and is subsequently characterised post-treatment by the presence of coordinated CCR7+ DC niches, clonally expanded IgG2 plasma cells, and the emergence of memory/ resident T-cell clonotypes. Conversely, acquired resistance is characterised by an immune exclusion programme, defined by dysfunctional vasculature, TREM2+ macrophage enrichment, impaired DC niche organisation and peri-vascular immunosuppressive niches. By identifying spatially resolved cellular niches underpinning differential responses to combination ICI approaches, this work provides insights into biomarkers of durable response, whilst providing a framework for rational combination strategies to overcome resistance.
The rapid growth of Autonomous Aerial Vehicles (AAVs) has underscored their importance across commercial and civil applications. Combining multi-AAVs with Deep Reinforcement Learning (DRL) approaches can achieve significant results, particularly in navigation and path-planning operations. Nevertheless, collaborative decision-making among AAV swarms faces major challenges, including handling partial observability and re-path planning under uncertainty. To address these challenges, we propose an Adaptive Distributional deep Q-network Graph ATtention (ADGAT) learning framework with a Partially Observable Markov Decision Process (POMDP) modeling approach to perform effective AAV swarm navigation. The proposed ADGAT framework combines an adaptive Distributional Deep Q-Network (Di-DQN) reinforcement learning algorithm with a multi-head Graph Attention (GAT) mechanism to enable effective decision-making by distributing rewards rather than estimating the expected value. Additionally, the GAT mechanism enhances each AAV's capabilities by aggregating information from neighboring AAVs. We compare the proposed ADGAT framework against state-of-the-art baselines and validate it using three key performance metrics, achieving an average success rate of 98%, a collision rate of 3%, and a path efficiency of 96%. The extensive simulation results prove the adaptability of the ADGAT framework for enhancing AAV swarm navigation in partially observable spaces.
Background: Dementia represents a major global public health challenge in aging populations, requiring effective primary care identification and prevention strategies. This study evaluated the prevalence and clinical significance of 11 modifiable risk factors among older adults within a primary healthcare setting. Methods: An observational, retrospective-analytical study was conducted in January 2025 within a family medicine team panel (N = 1122). Participants aged 65 and older were divided into two cohorts: patients with diagnosed dementia (n = 20) and a comparative group without dementia (n = 50). Data on 11 modifiable risk factors were extracted using medical records and clinical anamnesis. Continuous variables were analyzed using Student’s independent samples t-test, while categorical variables were evaluated using Pearson’s chi-square test or Fisher’s exact test (p < 0.05). Results: Patients with dementia were significantly older (85.50 ± 4.83 vs. 80.34 ± 4.10 years; p < 0.05). Lower educational level was frequent among dementia patients, with 55% (n = 11) having completed primary education compared to 32% (n = 16) in controls (p = 0.160). Obesity (BMI > 30 kg/m²) was significantly less frequent in the dementia group (5%, n = 1 vs. 48%, n = 24; p < 0.05). Arterial hypertension showed a lower prevalence in dementia patients (85%, n = 17 vs. 98%, n = 49; p = 0.038). Hearing impairment was present in all participants (100%). In late life, physical inactivity (90%, n = 18 vs. 74%, n = 37; p = 0.141), social isolation (60%, n = 12 vs. 66%, n = 33; p = 0.636), and depression (55%, n = 11 vs. 64%, n = 32; p = 0.485) showed high overall prevalence across both cohorts without statistically significant group differences. Conclusion: Modifiable risk factors for dementia are highly prevalent among geriatric primary care patients, representing a widespread cumulative burden. Early identification and systematic screening in family medicine are essential to optimize cognitive health management.
ABSTRACT Introduction Visceral hypersensitivity (VHS) is considered a hallmark of irritable bowel syndrome (IBS) characterized by altered thresholds for rectal pain and discomfort during rectal distention. Rectal distention can also elicit the urge to defecate, a normal physical sensation that is, reported more often in IBS and may involve mechanisms distinct from pain and discomfort. This study investigates clinical, psychological, and physiological correlates of increased urge to defecate in IBS compared with healthy controls (HC), including sex‐based differences. Methods Patients with IBS (Rome III criteria) and HC underwent rectal balloon‐distension and completed questionnaires on demographics, lifestyle, gastrointestinal (GI) and psychological symptoms, and health‐related quality of life (HrQoL). Latent clusters were identified using finite‐mixture modeling, and associated determinants were evaluated using multivariable logistic regression analyses. Results Among 322 participants (220 IBS, 102 HC), the occurrence of the urge to defecate was more frequent in IBS than in HC (80.9% vs. 51.9%; p < 0.001) and often co‐occurred with rectal pain and discomfort, particularly in patients with VHS. Latent class analysis identified three clusters, primarily distinguished by rectal symptom‐distribution, with the most symptomatic cluster showing greater GI‐symptom severity, higher psychological burden, and lower HrQoL (all p < 0.001). Regression analyses confirmed associations of urge with GI symptom severity, depressive symptom scores, and co‐occurrence of pain/discomfort, but no association was found based on IBS subtype or sex. Conclusion Increased urge to defecate is highly prevalent in IBS, strongly associated with rectal pain, rectal discomfort, psychological burden, and reduced HrQoL, but not in the IBS subtype, suggesting shared or overlapping mechanisms, particularly in the context of VHS. These findings underscore its clinical and pathophysiological relevance, supporting its value for patient‐phenotyping and tailored management. Trial Registration The Maastricht Irritable Bowel Syndrome (MIBS) cohort study was registered under the registration number NCT00775060
Older adults represent a rapidly expanding subgroup of patients with inflammatory bowel disease, yet they remain markedly under-represented in pivotal clinical trials, limiting age-specific estimates of drug benefit and harm. This review synthesises the available evidence on the influence of ageing on the pharmacology, efficacy and safety of orally administered targeted inflammatory bowel disease therapies, focusing on registered Janus kinase inhibitors (tofacitinib, upadacitinib, filgotinib) and sphingosine-1-phosphate receptor modulators (ozanimod, etrasimod). Because the available age-stratified evidence is sparse and heterogeneous, a narrative review methodology was chosen to map the literature and identify knowledge gaps. We pragmatically report age-related findings using the age cut-offs applied in original studies and map outcomes including clinical and endoscopic response/remission, corticosteroid sparing and adverse drug events of special interest (serious/opportunistic infections, cardiovascular and thromboembolic events, malignancies and treatment discontinuation). Across the limited age-stratified datasets, efficacy appears largely maintained in older patients, but the evidence base is heterogeneous and frequently lacks dedicated analyses. Ageing-related physiological changes, comorbidity, frailty and polypharmacy are expected to modulate pharmacokinetic and pharmacodynamic variability and to amplify the clinical relevance of class-specific safety concerns, particularly infections, major adverse cardiovascular events and malignancy signals with Janus kinase inhibition and initiation-related cardiovascular/conduction considerations with sphingosine-1-phosphate modulation. There is, however, no clear consensus on how ageing-related vulnerability, including frailty and comorbidity burden, should be defined, measured, and reported across studies, which complicates the interpretation and comparison of outcomes. In the absence of robust outcome data for older adults with inflammatory bowel disease, treatment selection should be guided by biological vulnerability (frailty, organ function, comorbidity burden) and structured risk-mitigation strategies, while future research should prioritise age- and frailty-enriched prospective studies with geriatric-relevant outcomes and long-term pharmacovigilance.
Cardiovascular–kidney–metabolic (CKM) syndrome is driven by the interplay of visceral adiposity, insulin resistance, chronic inflammation, oxidative stress, and progressive kidney dysfunction. These mechanisms generate a distinct atherogenic dyslipidaemic phenotype characterised by elevated triglycerides (TG), reduced high-density lipoprotein-cholesterol (HDL-C), increased apolipoprotein B (apoB)-containing lipoproteins, remnant cholesterol (RC) accumulation, small dense low-density lipoprotein (LDL) particles, and frequently elevated lipoprotein(a) [Lp(a)]. Such lipid abnormalities contribute to accelerated atherosclerosis and early renal deterioration. In turn, kidney dysfunction further amplifies lipid abnormalities. These pathways underscore the need for a timely and comprehensive lipid assessment using apoB, non-HDL-C, RC, and Lp(a) within the CKM framework. Effective lipid management is crucial for CKM syndrome treatment, with the potential to reduce residual cardiovascular and renal risk and improve long-term clinical outcomes. In this narrative review, we examine current evidence on the pathophysiological mechanisms underlying CKM-related dyslipidaemia and provide a practical framework for its assessment and management. Management requires a multimodal approach tailored to the patient’s lipid phenotype and overall cardiovascular risk, incorporating a range of lipid-lowering strategies including statins, ezetimibe, PCSK9 inhibitors, bempedoic acid, fibrates, icosapent ethyl, and emerging therapies targeting apoC-III, ANGPTL3, and Lp(a). Beyond lipid lowering, lifestyle interventions and cardiometabolic therapies such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and finerenone may provide complementary cardiometabolic and renal protection.
The composition of the growing medium is a key factor in the long-term functionality of green roofs, and in recent years, increasing attention has been paid to the use of biochar and other recycled organic materials. The use of biochar in green roof substrates represents an innovative way to improve their hydrological and nutritional properties in accordance with the principles of the circular economy. As part of this study, we incorporated 8.2% organic additives into the experimental substrates, including dried sewage sludge, biochar derived from sewage sludge, food waste biochar, wood biochar, and sewage sludge compost. The main hypothesis was that these additives would induce significant changes in the physicochemical properties of the substrate, nutrient content, and heavy metal concentrations, affecting plant growth. The study involved a three-year monitoring of six modules planted with a mixture of twelve Sedum species. The results showed that dried sewage sludge, food waste biochar, and sludge compost had a highly positive effect on vegetation growth, with coverage significantly higher compared to the control sample. The highest average coverage of plants (89%) was achieved by the substrate with dried sewage sludge due to its high content of available nitrogen and phosphorus. Wood biochar exhibited higher soil moisture content (mean 21.28%) and its stability throughout the year, but without a significant positive effect on plant growth. Dried sewage sludge applications improved soil quality the best with increase in the availability of essential nutrients NPK (an 87% increase compared to the control module). Several heavy metals (notably Cd, Cr, Zn, and Hg) exceeded regulatory thresholds, indicating a potential environmental risk that requires further investigation, particularly with respect to long-term accumulation and leaching.
Abstract Background: The total number of platelets (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) are utilized as markers of platelet activation in assessing thrombotic vascular events. Given the critical importance of maintaining adequate vascular access, i.e., arteriovenous (AV) fistula, for the survival of hemodialysis (HD) patients, the question arises: Is it possible to detect changes in platelet parameters that indicate a connection to occurrences of thrombotic complications with AV fistula? Materials and methods: The study involved 100 patients diagnosed with end-stace renal disease, admitted to the Clinic of Hemodialysis at the University Clinical Center Sarajevo (UCCS). All patients underwent standard bicarbonate HD three times a week, utilizing a native AV fistula for access. The study group was divided into two subgroups: patients without confirmed AV fistula thmmbosis (AVF-nonT; n = 66) and patients with confirmed AV fistula thrombosis (AVF-T; n = 34). Anamnestic data and platelet parameter values were collected during the surveyed period. Results: The average value of the PLT was significantly lower (p = 0.001), while the average value of the MPV was significantly higher (p = 0.0001) in patients of the AVF-T group in relation to the patients in the AVF-nonT group. In differentiating patients of the AVF-T group and patients of the AVF-nonT group, PLT in peripheral blood had a moderately good diagnostic accuracy (AUC = 0.704; p = 0.001), and MPV had an excellent diagnostic accuracy (AUC = 0.991; p < 0.001). Conclusion: PLT and MPV can be used as effective biomarkers ofAV fistula thrombosis in patients undergoing chronic HD treatment.
Background/Objectives: Previous studies have linked chronic conditions and multimorbidity to lower physical activity, but evidence across individual movement behaviours remains limited. We examined associations between the number of self-reported chronic diseases and conditions and transport-related walking, leisure time physical activity, muscle-strengthening activity and sedentary behaviour among people aged ≥15 years in Serbia. Methods: Nationally representative 2019 Serbian National Health Survey data were analysed (n = 13,076 with complete information on 17 conditions). Complex sample logistic regression models were sequentially adjusted for sociodemographic characteristics, body mass index, functional mobility and self-rated health. Additional analyses assessed linear trends and departures from linearity using all covariates except self-rated health. Results: Overall, 51.4% reported no condition, 18.0% one and 30.6% two or more. All outcomes were associated with condition status before adjustment, but most associations were attenuated after including functional mobility. After full adjustment, an overall association remained only for muscle-strengthening activity on <2 days/week (Wald F = 5.13; p = 0.006). Compared with no condition, one condition was associated with higher odds (aOR 1.60, 95% CI 1.18–2.16), but two or more were not. Each additional condition was associated with 4.5% higher odds of sitting or reclining for ≥6 h/day (aOR 1.045, 95% CI 1.006–1.087; p = 0.025). No other linear trends were identified; muscle-strengthening activity showed a departure from linearity (p < 0.001). Conclusions: Associations differed across movement behaviour domains and were attenuated particularly after including functional mobility. The number of conditions alone only partially accounted for observed differences in movement behaviours.
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