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Northwest China is characterized by severe water scarcity, and cloud water represents an important potential supplement to regional water availability. Cloud water path is a key physical parameter for quantitatively characterizing cloud water resources; understanding its variability and associated influencing factors is essential for the scientific assessment and sustainable utilization of regional cloud water resources. In this study, ERA5 and JRA-3Q reanalysis datasets (1960–2025) and satellite cloud products from MODIS and Cloud_cci (2003–2016) were used to evaluate the consistency of multi-source datasets in capturing cloud water path variations. Following the assessment of ERA5 applicability through multi-source comparisons, trend analysis, change-point detection, and ensemble empirical mode decomposition (EEMD) were applied to characterize the multi-timescale variability of cloud water path. Furthermore, the associations of cloud water path variability with climatic and environmental factors, including atmospheric circulation, aerosol optical depth (AOD), global mean surface temperature (GMST) anomaly, and the El Niño–Southern Oscillation (ENSO), were investigated. The results indicated these datasets generally agreed on the temporal variability of cloud water path, whereas differences were found in the absolute ice water path (IWP) and total cloud water path (CWP) values and estimated long-term trends. IWP contributed substantially to CWP variability across most timescales, while the long-term evolution of CWP reflected changes in both liquid water path (LWP) and IWP. LWP, IWP, and CWP showed gradual increasing tendencies, with no significant change points detected. EEMD analysis suggested variability components at approximately 3-year and 7–9-year timescales with relatively large variance contributions, although these components were not statistically significant. Cloud water path variability showed different relationships with climatic and environmental factors. The IWP IMF1 component, with an approximately 3-year timescale, exhibited a weak positive association with the mid-latitude westerly index, whereas no stable linear relationships were detected between cloud water path and summer monsoon or ENSO variability. IWP and CWP showed significant seasonal correlations with AOD, which may largely be attributable to their shared seasonal variations. After detrending, IWP exhibited a weak negative correlation with GMST anomaly. Full article

Background: Endotoxemia and oxidative stress may contribute to adverse body-composition changes in patients receiving maintenance hemodialysis, but their relationships with adiposity and muscularity remain incompletely defined. We investigated whether the concentrations of circulating lipopolysaccharide (LPS), soluble NOX2-derived peptide (sNox2-dp), and hydrogen peroxide (H₂O₂) showed differential associations with bioimpedance-derived body-composition compartments and explored their relationships with normalized protein catabolic rate (nPCR), a surrogate of protein intake. Methods: In this observational, cross-sectional study, adult patients receiving maintenance hemodialysis were enrolled at a single center. Serum LPS and sNox2-dp and H₂O₂ concentrations were measured before dialysis. Body composition was assessed by bioimpedance analysis; fat mass (FM) was used as an index of adiposity, whereas intracellular water indexed to height squared (ICW/h²) was used as a proxy of muscularity. Associations were examined using Spearman correlation and multivariable linear regression adjusted for age, sex, and nPCR. Results: A total of 58 participants were included with a median age of 73 years; 64% were male and mean body mass index was 24.6 ± 4.2 kg/m². LPS correlated with sNox2-dp (rho = 0.420, p = 0.001), whereas sNox2-dp correlated with H₂O₂ (rho = 0.352, p = 0.007); the LPS–H₂O₂ association was borderline (rho = 0.259, p = 0.050). sNox2-dp correlated positively with fat-free mass, total body water, ICW, and ICW/h², whereas LPS correlated with FM (rho = 0.305, p = 0.023). Participants with nPCR > 0.89 g/kg/day had higher LPS concentrations than those with lower nPCR (p = 0.015), and nPCR correlated with ICW/h² (rho = 0.36, p = 0.007). In multivariable analysis, LPS remained independently associated with FM (β = 0.210, p = 0.046). nPCR was positively associated with ICW/h² at the threshold of statistical significance (β = 1.393, p = 0.050), whereas sNox2-dp showed a nonsignificant positive trend (p = 0.060). Conclusions: In maintenance hemodialysis, endotoxemia and NOX2 activation showed differential associations with body composition: LPS with adiposity and sNox2-dp with muscularity. Higher nPCR was associated with both greater muscularity and higher LPS concentrations, suggesting a complex relationship between protein intake, the gut–oxidative-stress axis, and body composition. Full article

Background: Adipose tissue insulin resistance (Adipo-IR) is a key driver in the pathogenesis of cardiometabolic diseases. Dyslipidemia, particularly elevated remnant cholesterol (RC), is also strongly associated with cardiometabolic risk and has been recognized as a highly atherogenic lipid marker. Although systemic IR is known to be linked to dyslipidemia and elevated RC, the specific relationship between Adipo-IR and RC remains unclear. This study aimed to investigate the association between Adipo-IR and RC as well as its consistency across different subgroups. Methods: A cross-sectional study was conducted involving 6299 Chinese subjects. Logistic regression was used to assess the associations between Adipo-IR quartiles and elevated calculated RC levels. Restricted cubic splines (RCS) and a two-piecewise model were employed to characterize the dose–response relationship. Subgroup analyses were performed by age, sex, and body mass index (BMI). Results: Participants in higher Adipo-IR quartiles exhibited a significantly increased risk of elevated RC, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) (all p for trend <0.001). After full adjustment, the odds ratios (95% CI) for the highest versus lowest Adipo-IR quartile were 1.90 (1.58–2.29) for RC, 1.76 (1.47–2.12) for LDL-C, and 4.74 (3.85–5.86) for TG. RCS analysis revealed a nonlinear increasing relationship between Adipo-IR and RC (p for nonlinearity <0.001). An estimated inflection point was identified at an Adipo-IR value of 44.85, with a significant positive association below this point (OR = 1.020, p < 0.001) but not above it (OR = 0.997, p = 0.248). This positive association was generally consistent across age, sex, and BMI subgroups, and interaction tests were not statistically significant except for the Q3 comparison by sex. Conclusions: Adipo-IR showed a nonlinear association with elevated calculated RC, with a positive association below the estimated inflection point of 44.85 in this cohort of Chinese adults. Full article

Background and Objectives: Visual evoked potentials (VEPs) are established tools for detecting optic pathway involvement in multiple sclerosis (MS); however, the distinct clinical significance of longitudinal changes in latency and amplitude remains unclear. This exploratory study aimed to evaluate the clinical utility of serial VEP assessments in patients with relapsing–remitting MS (RRMS) by examining the associations between temporal changes in latency and amplitude and concurrent markers of disease activity and disability. Materials and Methods: We retrospectively analyzed 83 patients with RRMS from three centers who underwent at least two pattern-reversal VEP assessments ≥ 1 year apart. Patients with recent optic neuritis were excluded. Longitudinal changes in VEP latency and amplitude were evaluated in relation to relapse activity during the same inter-assessment interval, baseline MRI and CSF findings, and disability assessed by the Expanded Disability Status Scale (EDSS). Sensitivity analyses were stratified and adjusted for disease-modifying therapy (DMT) efficacy tier, and progression independent of relapse activity (PIRA) was examined using a formal definition. Results: Over a median follow-up of 2 years, 43.4% of patients developed P100 latency prolongation, which was independently associated with a higher annualized relapse rate during the same interval (odds ratio [OR] 2.91, p = 0.005; area under the curve (AUC) 0.72 for concurrent on-study relapse activity), an association that persisted after adjustment for DMT efficacy tier, but not with disability worsening. In contrast, 56.6% of patients exhibited amplitude reduction, which was associated with greater disability accumulation at the group level, with higher EDSS scores at follow-up despite similar baseline values (p < 0.05); the corresponding inverse correlation between amplitude decline and EDSS change was only nominally significant (ρ = −0.231, p = 0.036), did not survive correction for multiple comparisons, and was attenuated after adjustment for baseline EDSS. Formally defined PIRA events were rare (n = 3), precluding inference. Baseline magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings differed in the latency group, with fewer MRI lesions and a lower immunoglobulin G (IgG) index, whereas no corresponding differences were observed in the amplitude group. Conclusions: In this exploratory cohort, longitudinal prolongation of VEP latency was associated with concurrent relapse activity, whereas amplitude decline showed a weaker, group-level association with disability. These findings are consistent with, but do not demonstrate, distinct inflammatory and neurodegenerative substrates, and warrant prospective validation before serial VEP monitoring can inform individualized management in MS. Full article

Background: The incidence of ulcerative colitis (UC) continues to rise, and food-derived bioactive peptides have attracted increasing attention as potential nutritional interventions for intestinal inflammation. This study investigated the preventive effects of the adzuki bean-derived peptide IFNNDPNNHP (IP10 peptide) on dextran sulfate sodium (DSS)-induced acute colitis in mice and explored the involvement of the gut microbiota. Methods: Mice received prophylactic IP10 peptide at 100 or 200 mg·kg⁻¹. Colitis severity was assessed based on body weight, disease activity index, colon length, histopathology, and inflammatory cytokine levels. Gut microbiota composition was analyzed by 16S rRNA gene sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT) were used to further evaluate the role of the gut microbiota. Results: Prophylactic IP10 peptide administration attenuated DSS-induced colitis, with the 200 mg·kg⁻¹ dose more effectively attenuating body weight loss and colon shortening, reducing disease activity index scores, and modulating inflammatory cytokine levels. IP10 peptide increased microbial richness and diversity, decreased the relative abundance of Escherichia-Shigella, and increased the relative abundances of SCFA-associated taxa, including norank_f__Muribaculaceae and Lachnospiraceae_NK4A136_group. It also increased fecal SCFA levels, particularly acetate and butyrate; the high dose additionally restored propionate and valerate. When the gut microbiota was depleted using antibiotics, the protective effects of the IP10 peptide were no longer detectable, whereas FMT using fecal microbiota from donors receiving the high dose of IP10 peptide attenuated colitis and increased fecal SCFA levels in recipient mice. Conclusions: IP10 peptide alleviates DSS-induced acute colitis, and this effect may be partly associated with alterations in the gut microbiota, including the enrichment of SCFA-associated taxa and increased fecal SCFA levels. These findings support its potential as a functional food ingredient for intestinal health. Full article

Background/Objectives: The omega-3 index, defined as the percentage of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes, is an established biomarker of long-term omega-3 fatty acid status and cardiometabolic disease risk in clinical populations. The primary purpose of this cross-sectional study was to determine the prevalence of National Collegiate Athletic Association Division III men’s and women’s collegiate athletes with an Omega-3 Index below the recommended threshold of 4%. Methods: Fifty (male, n = 21; female, n = 29) collegiate athletes completed a single testing session including anthropometrics, body composition, resting heart rate (HR) and blood pressure assessment, and venous blood sampling for determination of Omega-3 Index, complete blood counts, and lipid profiles. The cardiovascular risk factors examined were total cholesterol, HDL, LDL, body mass index, body composition, waist-to-hip ratio, resting hemodynamics, and blood glucose. Results: Overall, 54% of athletes exhibited an Omega-3 Index < 4%, while 100% had an Omega-3 Index < 8%. Male athletes demonstrated significantly higher Omega-3 Index, total omega-3 fatty acid levels, and lower omega-6:omega-3 ratios than females (p ≤ 0.005; ηp² = 0.154–0.194). Pearson correlation analyses revealed few significant correlations between Omega-3 Index and cardiometabolic disease risk factors, with only weak relationships observed for systolic blood pressure (r = 0.284, p = 0.046) and triglycerides (r = −0.348, p = 0.035). Conclusions: Suboptimal omega-3 status was highly prevalent among collegiate athletes, with no participant achieving the cardioprotective Omega-3 Index threshold of ≥8%. Although male athletes demonstrated a more favorable omega-3 fatty acid profile than females, Omega-3 Index exhibited limited correlations with traditional cardiometabolic disease risk factors in this young, healthy population. Full article

Background/Objectives: The C-reactive protein–albumin–lymphocyte (CALLY) index integrates systemic inflammation, nutritional status, and host immunity. We evaluated its association with postoperative pathological axillary nodal status and its incremental discrimination beyond routinely recorded preoperative clinical factors. Methods: This retrospective single-center diagnostic-accuracy study screened 380 patients evaluated between July 2019 and January 2026. The primary cohort included 247 unilateral M0 patients undergoing upfront surgery; 80 neoadjuvant-treated M0 patients were analyzed separately. CALLY was calculated from laboratory values obtained within 7 days before surgery. Associations and discrimination were assessed using logistic regression, Firth penalized logistic regression when clinical nodal status caused separation, paired bootstrap AUC comparisons, restricted cubic splines, and prespecified sensitivity analyses for BMI and available inflammatory/comorbidity covariates. Results: In the primary cohort, 75 patients (30.4%) were pN-positive. Median CALLY was 2.629 in pN-positive and 3.586 in pN0 patients (p = 0.058), and standalone discrimination was weak (AUC = 0.576; 95% CI, 0.496–0.651). In the age- and cT-adjusted model, the OR per CALLY doubling was 0.89 (95% CI, 0.72–1.10; p = 0.271). Preoperative cN status nearly separated the outcome; in a Firth model including age, cT, cN, and CALLY, the CALLY OR was 0.78 (profile 95% CI, 0.51–1.21; p = 0.250). Adding CALLY to age, cT, and cN changed the AUC from 0.988 to 0.988 (ΔAUC = −0.0001; 95% CI, −0.0013 to 0.0041; p = 0.551). No nonlinearity was detected (p = 0.352), and BMI/confounder sensitivities were concordant. Secondary neoadjuvant and observed-burden analyses remained exploratory and imprecise. Conclusions: In this single-center upfront-surgery cohort, preoperative CALLY was not independently associated with postoperative axillary nodal positivity and provided no convincing incremental discrimination beyond the available clinical assessment. The data do not support using CALLY alone for axillary staging or surgical decisions; limited high-burden event counts preclude a definitive exclusion of smaller associations. Full article

Groundwater is the main source of drinking, irrigation, and ecological water in the Baiyangdian Lake Basin (BLB), but growing human activity has raised concerns about its quality. This study assesses major ion geochemistry and multi-receptor environmental risks across the BLB using 1113 groundwater samples (983 shallow, 130 deep). Risks to drinking water supply, agricultural irrigation, and wetland health are evaluated within a single framework, and Positive Matrix Factorization (PMF) is used for quantitative source apportionment. Shallow groundwater shows markedly higher dissolved solids and nitrate than deep groundwater, with 20.7% of shallow samples exceeding the WHO nitrate guideline. Multi-receptor assessment finds that 41.2% of shallow wells pose risk to at least one endpoint and 12.5% to two or more simultaneously. PMF identifies three sources—geogenic weathering, agricultural nitrate, and wastewater discharge—with nitrate as the largest single contributor to water quality impairment. The findings point to an urgent need for targeted agricultural non-point source control and provide a basis for nested, multi-scale groundwater management in the BLB and similar intensively exploited alluvial aquifers. Full article

Background/Objectives: Diet quality is an important determinant of health during young adulthood; however, associations between dietary behaviours and anthropometric outcomes in university students remain insufficiently understood. This study examined the associations between dietary behaviours and anthropometric indicators in Chilean university students. Methods: A cross-sectional study was conducted among university students from southern Chile between June and November 2025. Dietary habits were assessed using a validated Chilean dietary habits questionnaire, from which Healthy Eating, Unhealthy Eating, and Overall Diet scores were derived. Anthropometric measurements included body mass index (BMI), waist circumference, and waist-to-height ratio (WHtR). Age- and sex-adjusted multivariable linear regression models were fitted. Exploratory analyses included psychometric evaluation, principal component analysis, false discovery rate (FDR) correction, and dietary behaviour network analysis. Results: A total of 374 students were included, of whom 40.3% were women. Psychometric analyses provided only partial support for the predefined two-domain structure, with stronger properties for the healthy domain. None of the predefined dietary scores were associated with BMI. The Unhealthy Eating Score was nominally positively associated with waist circumference (β = 0.285 cm per score point, 95% CI: 0.011–0.560), although this association did not remain statistically significant after FDR correction. Exploratory item-level analyses identified positive associations between sugar-sweetened beverage consumption and waist circumference and inverse associations between breakfast consumption and BMI after FDR correction. Conclusions: Predefined dietary behaviour scores showed limited associations with anthropometric outcomes. Psychometric analyses provided only partial support for the predefined scoring structure, particularly for the unhealthy dietary domain. Exploratory item-level analyses suggested that specific dietary behaviours may provide complementary information beyond that obtained by composite dietary scores, although these findings require confirmation in prospective longitudinal studies and further psychometric validation. Full article

Psoriasis is a chronic immune-mediated skin disease associated with systemic inflammation and multiple environmental triggers, including microbial colonization and infections. However, the relationship between upper respiratory tract microorganisms and the clinical characteristics of plaque psoriasis and psoriatic arthritis remains incompletely understood. This retrospective study analyzed 624 patients with plaque psoriasis, including mild and moderate-to-severe disease, and psoriatic arthritis who presented with upper respiratory tract symptoms and clinical signs suggestive of pharyngeal involvement. Upper respiratory tract swabs were evaluated using culture-based methods. Clinical and inflammatory parameters, including disease severity assessed using the Psoriasis Area and Severity Index (PASI), systemic inflammation assessed using C-reactive protein (CRP), body mass index (BMI), age, sex, and smoking status, were analyzed. All patients were evaluated prior to initiation of systemic antipsoriatic treatment. Overweight and obesity were prevalent and were associated with higher CRP levels across clinical groups. Culture-positive results were identified in 247 patients, yielding 275 isolates, while 377 patients had culture-negative results with physiological flora only. The distribution of the most frequently isolated microorganisms was broadly similar across clinical subgroups, with limited variation according to psoriasis severity or psoriatic arthritis status. Multivariable analysis identified CRP and PASI as the most consistent factors associated with culture positivity in selected subgroups, with evidence of an interaction between psoriasis severity and systemic inflammatory burden. No consistent associations were observed between specific microorganisms and clinical measures of disease severity. Overall, systemic inflammatory and metabolic parameters showed more consistent associations with culture-positive pharyngeal findings than individual culture-detectable microorganisms. Given the retrospective design, symptom-based inclusion, and absence of a contemporaneous control group, these findings should be interpreted as descriptive and associative rather than causal. Prospective controlled studies using standardized sampling and culture-independent methods are needed to clarify the clinical significance and temporal relationship between upper respiratory tract microbial findings and psoriasis activity. Full article

Reliable assessments of the operational conditions of LED lighting systems are important for maintenance planning and asset management. Conventional Wear Index (WI) approaches typically assume a fixed daily number of switching cycles, which may not accurately reflect actual operating conditions. This study proposes a machine learning-based framework for operational Wear Index estimation using measured switching-cycle data collected from an LED lighting installation. Daily energy consumption and operating time were predicted using Multiple Linear Regression (MLR), Random Forest (RF), Long Short-Term Memory (LSTM), and Backpropagation Neural Network (BPNN) models. The models were evaluated using consistent performance metrics, and the BPNN achieved the highest predictive accuracy and was subsequently applied to the Wear Index calculation. Incorporating measured daily switching activity instead of the conventional fixed assumption of nine switching cycles per day resulted in a 17.80% higher cumulative Wear Index. This result demonstrates that the representation of switching activity can materially influence operational wear assessment. The proposed framework provides a practical data-driven approach for estimating operational wear under actual operating conditions and may support maintenance planning in intelligent lighting systems. Since the results are based on a single monitored installation, they should be interpreted as a case study. Full article

Background/Objectives: Guizhi Fuling Capsule (GZFL), a Traditional Chinese Medicine (TCM) formula, is widely used for primary dysmenorrhea and other blood-stasis gynecological disorders. This study aimed to characterize its material basis, elucidate its multi-component, multi-target mechanism against acute primary dysmenorrhea, and establish an integrated pharmacokinetic-pharmacometabolomic-pharmacodynamic (PK-PM-PD) framework for TCM efficacy evaluation. Methods: GZFL constituents and serum metabolites in an oxytocin-/estradiol-induced rat dysmenorrhea model were characterized by UPLC/Q-TOF-MS. Uterine effects of GZFL-containing serum were assessed ex vivo. The active components of GZFL were screened by Chinmedomics, with candidate targets investigated through network pharmacology, transcriptomics, and molecular docking. In total, 23 pharmacodynamic indicators were integrated by principal component analysis into an Efficacy Index (EI). Correlation analysis between pharmacometabolomic and pharmacodynamic data yielded a Metabolite-Efficacy Index (MEI), evaluated across a 21-day time course. Results: Among 197 constituents characterized in GZFL extract, 136 serum-exposed components were detected, with several key metabolites enriched via biotransformation. GZFL-containing serum bidirectionally regulated uterine contractility toward the control level. Integrated analyses revealed 68 candidate therapeutic targets. GZFL suppressed NF-κB/IKKβ signaling, down-regulated COX-2/iNOS, restored the PGF2α/PGE2 balance, and normalized inflammatory cytokines. Eleven efficacy-associated metabolites correlated with pharmacodynamic recovery were revealed and integrated, with MEI achieving the highest predictive performance among five integration strategies (AUC = 0.9) and robustly tracking the full 21-day disease-recovery trajectory. Conclusions: GZFL attenuates dysmenorrhea through coordinated regulation of inflammation, prostaglandin metabolism, and uterine functional homeostasis, rather than through inhibition of a single target. The PK-PM-PD framework, with EI and MEI, offers a reproducible paradigm for evaluating complex TCM therapies. Full article

Productivity evaluation in industrial software projects is still predominantly based on aggregate Function Point-to-effort ratios. Such an approach overlooks the internal structural and functional heterogeneity of software projects, potentially leading to misleading comparisons between systems characterized by similar functional sizes but markedly different structural complexities. This work investigates the hypothesis that projects with similar functional structures, within the same application domain, tend to exhibit comparable productivity behavior. For this purpose, an adaptive and structurally informed productivity assessment approach is proposed, based on a Structural Productivity Index that integrates domain-specific productivity information with project functional composition. The proposed model is validated through real-world and synthetic project datasets, combined with consistency indicators and clustering-based analyses to examine its behavior under different conditions and its capability to distinguish regular productivity patterns from structurally anomalous projects. Experimental results suggest that the proposed adaptive productivity modeling approach provides a more coherent interpretation of productivity estimates compared with traditional productivity metrics. The proposed structural representation provides an interpretable basis for future AI-based productivity analytics. Full article

The 2021 eruption of Cumbre Vieja on La Palma, Canary Islands, produced extensive lava flows and major landscape transformation, providing an opportunity to evaluate remote sensing approaches for mapping the extent of an emplaced lava flow. This study assessed direct spectral, classic Rao’s quadratic entropy (RaoQ), and multidimensional RaoQ approaches using satellite observations acquired before and after the eruption. Optical, radar, thermal infrared, and night-time radiance datasets were evaluated within a common change-detection framework implemented in Google Earth Engine. Difference maps were converted into binary change maps using a histogram-based thresholding procedure calibrated on the reference delineation and evaluated against the Copernicus Emergency Management Service (CEMS) lava-flow reference and no-change validation areas derived from ESA WorldCover using multiple accuracy metrics. Because the change reference is the final CEMS lava-flow delineation and the no-change samples lie outside a 100 m buffer around it, the accuracy figures reported here quantify the mapping of lava-flow extent and not of other eruption-related effects such as ash deposition or vegetation damage beyond the flow margins. Among the direct spectral approaches, the NHI_SWIR index achieved the highest overall classification performance. Among the individual Sentinel-2 bands, B12 achieved the highest overall accuracy, whereas B8A achieved the highest true skill statistic; both exceeded the multidimensional RaoQ configurations in mean prevalence-independent discrimination. Within the classic RaoQ approach, MIRBI produced the strongest single-variable heterogeneity-based results. The best multidimensional configurations combined Sentinel-2 B8A and B12 with Sentinel-1 VV, demonstrating that radar backscatter provided complementary information to optical observations. Although multidimensional RaoQ did not surpass the best direct spectral variables, it produced competitive and spatially coherent representations of lava-flow disturbance. The evaluated thermal infrared and night-time radiance products did not provide competitive discrimination under the selected spatial and temporal conditions for different reasons: a thresholding limitation in the case of the Landsat thermal product, and an unfavourable ratio of pixel size to flow width in the case of the night-time radiance products, while the MODIS product returned no valid validation points and could not be evaluated. These product-specific explanations rest on a small number of comparisons and are provisional. These results show that carefully selected Sentinel-2 SWIR variables remain the strongest benchmark for detailed mapping of fresh lava-flow disturbance, while multidimensional RaoQ provides a framework for optical–radar integration that requires no training data or prior classification. Because the evaluation covers a single eruption in a single landscape, transfer of the framework to other events and settings remains to be demonstrated. Full article

Background and Objectives: FOXP3+ (Forkhead box P3) regulatory T cells contribute to immune tolerance after kidney transplantation, but their role in T cell-mediated rejection (TCMR) remains controversial. This study investigated the association between intragraft FOXP3+ cells and the recently introduced Banff-derived activity (AI) and chronicity index (CI) in biopsy-proven TCMR. Materials and Methods: This retrospective cross-sectional study included 119 kidney allograft biopsies diagnosed as acute or chronic active TCMR according to the Banff classification. FOXP3+ cells were assessed by immunohistochemistry and expressed as cortical cell density (cells/mm²). Associations between FOXP3+ cell density, Banff-derived indices, inflammatory cell densities, and clinical parameters were analyzed using non-parametric statistical methods. Results: FOXP3+ cells were detected in 17.6% of biopsies. FOXP3+ cell density was univariately associated with higher CI values (ρ = 0.228, p = 0.013) and chronic lesions interstitial fibrosis (ci) (ρ = 0.284, p = 0.002) and tubular atrophy (ct) (ρ = 0.246, p = 0.008). No association was observed with AI or activity lesions, except for a weak negative correlation with interstitial inflammation (i) (ρ = −0.209, p = 0.025). In multivariable analysis, FOXP3 positivity was not significantly associated with CI after adjustment for transplantation–biopsy interval (B = 0.568, 95% CI −0.741–1.876, p = 0.391). FOXP3+ cell density positively correlated with cluster of diferentiation (CD)4+ (ρ = 0.350, p < 0.001), CD8+ (ρ = 0.229, p = 0.018), and CD163+ (ρ = 0.207, p = 0.047) cell densities. No association with short-term graft outcome was observed. Conclusions: FOXP3+ cell infiltration was associated with chronic histological changes in unadjusted analyses, but this association did not remain statistically significant after adjustment for transplantation-to-biopsy interval. These preliminary findings suggest that FOXP3+ cell accumulation and chronic histological changes may represent parallel time-dependent phenomena and require confirmation in larger cohorts. Full article