BackgroundMalnutrition is associated with poorer cognitive performance, though the evidence is predominately from Caucasian and urban populations. We aim to study the association between malnutrition, cognitive performance, and brain morphology in a rural southern Indian population.MethodWe used baseline cross‐sectional data from the Centre for Brain Research‐Srinivaspura Aging NeuroSenescence and COGnition (CBR‐SANSCOG) study cohort of non‐demented participants aged 45+ years (n = 3687). Malnutrition was assessed using multivariable indices‐ Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), CONUT (Controlling Nutritional Status) score, and anthropometric indices‐ body mass index (BMI) and mid‐upper arm circumference (MUAC). We assessed the agreement of each nutritional index with the Standard Combined Index (SCI). Cognitive performance was assessed using Hindi Mental Status Examination (HMSE) and culturally adapted COGNITO test battery (Computerized assessment of adult information processing). The domain‐specific (attention, memory, language, visuospatial) cognitive scores were standardized and a composite score was calculated from the weighted averages of the individual test scores. General linear model was used to assess the association between the malnutrition indices and cognitive performance, adjusting for age, sex, education, tobacco, alcohol use, hypertension, diabetes, and depression. In a subset of participants who underwent 3T MRI (n = 1150), region of interest (ROI)‐based analysis was done to study the association between the malnutrition indices and brain ROI volumes normalized for total intracranial volume, adjusting for age, sex, and education.ResultBased on MUAC, GNRI, PNI, and CONUT score, 8.8%, 9%, 15%, and 19% of the participants (mean age: 57.49±9 years) were at a risk of malnutrition, respectively. GNRI had the best agreement with the SCI. We found a positive association between GNRI, BMI, MUAC scores and cognitive performance (Table 1) and ROI brain volumes (Table 2). MUAC had a stronger relationship to cognitive domains than BMI. No association was observed between PNI and CONUT scores and any of the outcome variables.ConclusionGNRI, a multivariable malnutrition index is a reliable predictor of cognitive performance and brain morphology. Additionally, MUAC, a simple and cost‐effective anthropometric measure, could be a potential indicator of rural Indians at risk of cognitive impairment.

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent skeletal muscle disorder characterized by progressive, asymmetric muscle weakness, particularly affecting the face, shoulders, and upper arms. Although estimates in India are unavailable, it is fairly common in the Caucasian population, with prevalence rates ranging from 1 in 8000 to 1 in 20,000. The typical age of onset of symptoms is in the second decade of life, with some severe cases exhibiting symptoms before the age of 5 years; however, there is a wide variation in the order and progression rate of affected muscles. Classical features, such as scapular winging and foot drop, affect the patient’s quality of life. FSHD is an autosomal dominant inherited disease caused by epigenetic derepression of the 4q35 D4Z4 macrosatellite array, leading to the expression of the toxic DUX4 protein in adult muscles. Contraction of the D4Z4 array to <10 repeats is believed to cause the derepression of this region. Its unique etiology, the large size of the repeats (~3.2 kb), and significant clinical variability make diagnosis and care challenging. Diagnosis is based on characteristic clinical features and confirmed by DNA testing using Southern blotting. Underdiagnosis due to the nonavailability of diagnostic testing in the country is only now being addressed by the availability of newer techniques, such as optical genome mapping. In this context, this review provides an overview of clinical presentation, disease mechanisms, and recent developments in research and diagnostics worldwide in FSHD and focuses on providing an Indian perspective based on the limited information available.

Background: Exercise-induced cardiac remodelling results in electrocardiographic alterations that vary by sport and ethnicity. International screening criteria, derived primarily from Caucasian populations, may inadequately capture physiological variations in North African athletes. Aim: To establish electrocardiographic profiles of Moroccan university athletes using the Seattle International Criteria and to analyse sport-specific variations. Methods: This cross-sectional study enrolled 149 university athletes (79 male, 70 female, aged 18-25 years) from Hassan I University in Morocco, classified into endurance, mixed/team and strength/power sports. Standardised 12-lead electrocardiography was interpreted independently by two specialists. ANOVA and chi-square tests were used for statistical analysis, and effect sizes were reported. Results: Significant differences in heart rate between sports emerged (p < .001, η² = .124): endurance athletes showed lower rates (58.4 ± 11.2 bpm) compared to mixed/team athletes (65.1 ± 11.8 bpm) and strength/power athletes (68.9 ± 12.5 bpm). The prevalence of sinus bradycardia was higher in endurance athletes (47.5% vs. 27.0% in mixed/team and 25.0% in strength/power; p = .018). Training-related findings were frequent (34.9% sinus bradycardia overall), borderline findings occurred in 5.4-8.1% and abnormal findings were minimal (6.0%). Conclusions: Moroccan athletes demonstrate sport-specific electrocardiographic adaptations with lower abnormality rates than those reported in sub-Saharan African populations, suggesting North African heterogeneity. The findings challenge assumptions about continental generalisations and support region-specific regulatory frameworks rather than universally applicable criteria, especially among endurance athletes who show pronounced bradycardic adaptations.

Purpose: Current pediatric ophthalmology practice relies on adult reference values for optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) interpretation due to limited age-appropriate normative data, potentially leading to diagnostic misclassification. Methods: We conducted a prospective, cross-sectional study comparing OCT and OCT-A parameters between 37 healthy Caucasian children (1–17 years) and 28 adults (19–65 years) using identical Zeiss CIRRUS protocols. Parameters included peripapillary retinal nerve fiber layer (RNFL), macular thickness, ganglion cell-inner plexiform layer (GCIPL), optic nerve head (ONH) perfusion, and macular vascular density. Results: Children exhibited significantly thinner parafoveal macular thickness compared to adults (251.67 ± 21.32 vs. 270.36 ± 17.02 μm; p < 0.001) while RNFL thickness remained comparable. OCT-A demonstrated higher ONH perfusion in children across multiple sectors (p < 0.001). Within the pediatric cohort, younger children (1–9 years) showed higher macular vessel and perfusion density than older children (10–17 years). All pediatric scans achieved excellent image quality with no exclusions. Conclusions: Clinically significant age-related differences in retinal structure and vasculature necessitate pediatric-specific reference ranges. The demonstrated technical feasibility supports routine OCT/OCT-A implementation in pediatric practice with age-appropriate interpretation guidelines.

This meta-analysis aims to evaluate the association between interleukin-10 (IL-10) -819 C/T (rs1800871), -592 C/A (rs1800872) and -1082 A/G (rs1800896) polymorphisms and leprosy susceptibility by analyzing multiple genetic models in the Asian and Caucasian populations. A systematic literature search was conducted in PubMed, Web of Science, Google Scholar and Embase (January 2001 to February 2025) following PRISMA guidelines. Case-control studies reporting genotype distributions for IL-10 polymorphisms in leprosy cases and controls were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under allelic, recessive, dominant and over-dominant models. Heterogeneity was assessed using Cochran's Q test and the I2 statistic. Publication bias was evaluated using Egger's test and funnel plots. A total of 13 studies were included, comprising 5509 leprosy cases and 8135 controls. The -1082 A/G variant exhibited a significant protective effect across allelic (A vs. G OR = 0.73, 95% CI 0.59-0.91, p = 0.005), dominant (AA+AG vs. GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006) and the over-dominant models (AG vs. AA+ GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006). Under the dominant model, the -819 C/T (CC+CT vs. TT OR = 0.76, 95% CI 0.61-0.96, p = 0.02) and -592 C/A (CC+CA vs. AA OR = 0.71, 95% CI 0.52-0.97, p = 0.03) polymorphisms also showed significant protective effects, suggesting a potential role of heterozygosity in reducing leprosy susceptibility. Subgroup analysis indicated stronger protective effects in Asians. Power analysis confirmed that the included studies had sufficient sample sizes to detect significant associations (α error probability < 0.05). This meta-analysis supports the protective role of IL-10 polymorphisms, particularly the -1082 A (rs1800896) allele, in reducing leprosy susceptibility. These findings underscore the role of genetic variation in disease susceptibility and suggest that IL-10 polymorphisms could serve as biomarkers for leprosy susceptibility.

Post-traumatic stress disorder (PTSD) is diagnosed when a person experiences chronic psychological distress following a traumatic event that involves a real or perceived threat to life or bodily harm. Up to one-third of inflammatory bowel disease (IBD) patients report some PTSD symptoms due to their disease (IBD-PTS); however, most data are collected in Caucasian populations. IBD-PTS is associated with poorer outcomes. To our knowledge, this is the first study to evaluate IBD-PTS in Black and Latino/a patients. Adult IBD patients of Black and/or Latino/a race were recruited at 2 IBD clinics. Those meeting eligibility requirements completed these assessment tools online: PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), Adverse Childhood Experience (ACE) Questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ), and Demographic and Clinical Information. White, non-Hispanic IBD patients from a previously published dataset from IBD Partners were used for age- and sex-matched controls (2:1). In total, the study included 180 matched controls and 90 participants, including 57.8% of Black and Latino/a patients who had experienced extreme fear or threats to life/bodily harm related to IBD; 33.3% who scored ≥31 on the PCL-5 (minimum criteria for IBD-PTS) vs 12.8% of matched controls. Black and Latino/a patients also reported more severe IBD-PTS symptoms. Those with higher PCL-5 scores had more adverse childhood experiences and were more likely to have been hospitalized, had surgery, or used the emergency room for IBD. More severe IBD-PTS was associated with poorer HRQoL. Black and Latino/a IBD patients may have rates of IBD-PTS 2.5 times higher than White peers, with more severe PTSD symptoms. Prior nonmedical adverse life events may be risk factors for the development of IBD-PTS. Additional research is warranted.

The frequency of pathogenic variants (PVs) in HRAS in Caucasian populations with pheochromocytoma and paraganglioma (PPGL) is significantly lower than that in Chinese, which reflects the ethnic difference in genetic landscape. However, the clinical and biochemical characteristics of patients with HRAS-mutant PPGL are rarely reported. This study explored the clinical and biochemical profiles of Chinese patients with HRAS-mutant PPGL. This is a retrospective analysis of clinical and biochemical characteristics of patients with PPGL (N = 717). Data on demographics, tumor characteristics, blood/urine biochemistry, preoperative preparation, intraoperative hemodynamics, and perioperative complications were analyzed in patients with HRAS-mutant and non-HRAS PPGL. A total of 111 (15.5%) patients were with PPGL due to PVs in HRAS. Patients with HRAS-mutant PPGL had higher plasma metanephrine levels, an increased incidence of catecholamine-associated signs and symptoms (CAS), intraoperative hemodynamic instability (IHI) and intensive care unit (ICU) transfer right after surgery compared with those with non-HRAS tumor. Despite with similar tumor size, patients with HRAS-mutant PPGL had significantly higher plasma metanephrine levels, a higher incidence of presenting CAS and IHI than those with tumors due to PVs in other genes associated with kinase pathways. A significantly high catecholamine content in HRAS-mutant PPGL was associated with high levels of enzymes of catecholamine metabolism such as tyrosine hydroxylase and phenylethanolamine N-methyltransferase, which was independent of tumor locations. Patients with HRAS-mutant PPGL have higher plasma metanephrine levels and a higher risk of IHI and ICU transfer, which therefore requires personalized perioperative managements.

BackgroundCutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer in Asian, Caucasian, and Hispanic populations and its aggressive form contributes to significant morbidity and mortality. Chronic ultraviolet B (UVB) exposure is a major environmental carcinogen that drives cSCC initiation, progression, and immune evasion. Regulatory T cells (Tregs) are known mediators of UVB-induced immunosuppression; however, their direct involvement in the establishment of cSCC remains elusive.MethodsFlow cytometry was employed to quantify Treg populations in the skin and draining lymph nodes of UVB-exposed and untreated mice. The functional role of Tregs following UVB exposure was examined using a contact hypersensitivity assay, where Treg activity was modulated by anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4, anti-TIGIT, and anti-FR4 antibodies. The capacity of UVB to render mice susceptible to immunogenic cSCC tumor establishment was assessed under different UVB exposure regimens. Treg-modulating antibodies were administered following UVB treatment and prior to tumor implantation to explore whether UV-induced Treg manipulation can prevent cSCC tumor establishment.ResultsUVB irradiation for 5 consecutive days significantly increased the number of CD4+ Foxp3+ Tregs in both skin and skin-draining lymph nodes. These Tregs were shown to be suppressive in contact hypersensitivity assays. However, suppression was prevented following depletion of Tregs and/or avolition of their function using monoclonal antibodies. Consistently, chronic UVB exposure prior to tumor implantation permitted the establishment and growth of otherwise immunogenic cSCC tumors, which correlated with the expansion and recruitment of Tregs into the skin. Importantly, immunomodulation with anti-CTLA-4 or anti-FR4 after chronic UVB exposure effectively prevented cSCC establishment, indicating that the manipulation of UV-induced Tregs prevented the establishment and growth of immunogenic cSCC tumors.ConclusionOur findings show that the manipulation of UV-induced Tregs prevents early cSCC establishment. Thus, strategies aimed at modulating Treg function or abundance in the skin may represent a feasible therapeutic avenue for the prevention of cSCC tumor emergence in patients.

Uveal melanoma (UM), the most common primary intraocular malignancy in adults, shows racial disparities in incidence, genetic drivers, and clinical outcomes. While most prognostication models are based on Caucasian populations, Asians demonstrate distinct molecular profiles, necessitating population-specific risk stratification. This study analyzed 53 Asian UM tumors, 17 normal choroidal tissues (TRACE database), and 80 Caucasian UM samples (TCGA database). Differential gene analysis, immune microenvironment profiling, and survival modeling were performed. A 7-gene prognostic signature was developed by LASSO regression and validated across cohorts, with drug sensitivity predicted using GDSC2 data. The Asian UM exhibited 3,827 tumor-specific differentially expressed genes (DEGs) compared to the normal choroid, with enrichment in PI3K-Akt signalling, and 3,814 race-specific DEGs compared to Caucasians, suggesting specific disease pathways and variations in the tumor microenvironment. The tumor microenvironment in Asian UM exhibited increased immunological activation (M1 macrophages, PD-L1, CD8; p < 0.05), while Caucasian uveal melanoma was marked by immunosuppressive predominance (M2 macrophages, MDSCs). The seven-gene prognostic model (MMP2, LRAT, NOG, IHH, CDH18, MYH11, and SELE) exhibited strong predictive efficacy in Asians (AUC: 0.979, 0.924, and 0.984 for 1, 3, and 5-year survival) but was less successful in Caucasians. High-risk scores correlated with metastasis (12/26 vs. 4/27; p = 0.02) and had independent prognostic value. This cross-racial UM study reveals significant molecular and immune differences, indicating that Asian UM may be more responsive to immunotherapy The population-specific prognostic model improves our understanding of molecular differences in Asian and Caucasian UM, warranting further validation in multiethnic cohorts.

Varus and neutral coronal knee phenotypes dominate globally: insights from a systematic review and meta-analysis of the CPAK classification.

APOE is a well-known susceptibility gene for Alzheimer's disease (AD), with common alleles (APOE2, 3, and 4) extensively studied across ancestries. Recent studies identified significant associations between rare missense variants (RMVs) and AD in Caucasian populations, with unique RMVs reported in Japanese cohorts. Investigating the roles of common and rare APOE variants in AD and related traits in East Asians is important. We analyzed data from the Gwangju Alzheimer's and Related Dementias (GARD) cohort, consisting of over 16,000 participants with up to 10 years of follow-up in South Korea. APOE common genotypes (E3/3 as reference) and allelic doses (E2 and E4) were evaluated for associations with AD, cognitive traits, and brain imaging (MRI) measures, adjusting for age and sex. We will investigate the impact of APOE RMVs, including previously reported and Asian-specific variants, on AD and related traits. Meta-analyses will include Asian participants from large cohorts such as Asian Cohort for Alzheimer's Disease (ACAD), Alzheimer's Disease Genetics Consortium (ADGC), and UK Biobank (UKBB). After excluding MCI cases, 7,389 participants (1,949 AD cases, 5,440 controls) were analyzed. Odds ratios (ORs) increased with fewer E2 alleles and more E4 alleles, ranging from 0.65 to 9.15 compared to E3/3 genotypes. Allelic dose analysis showed a stronger effect for E4 (OR: 2.36) than E2 (OR: 0.83). Increased E4 alleles were associated with reduced hippocampal volume and entorhinal cortex thickness, while E2 showed no significant effects. Cognitive domains, including attention, visuospatial, memory, and frontal functions, declined with increasing E4 alleles but showed no significant associations with E2. APOE genotypes and allelic doses significantly influence AD and related traits. Comprehensive analysis of common and rare APOE variants, particularly in Asian populations with distinct risk profiles, is critical for understanding, treating, and preventing AD.

BackgroundMalnutrition is associated with poorer cognitive performance, though the evidence is predominately from Caucasian and urban populations. We aim to study the association between malnutrition, cognitive performance, and brain morphology in a rural southern Indian population.MethodWe used baseline cross‐sectional data from the Centre for Brain Research‐Srinivaspura Aging NeuroSenescence and COGnition(CBR‐SANSCOG) study cohort of non‐demented participants aged 45+ years(n = 3687). Malnutrition was assessed using multivariable indices‐ Geriatric Nutritional Risk Index(GNRI), Prognostic Nutritional Index(PNI), CONUT(Controlling Nutritional Status) score, and anthropometric indices‐ body mass index(BMI) and mid‐upper arm circumference(MUAC). We assessed the agreement of each nutritional index with the Standard Combined Index (SCI). Cognitive performance was assessed using Hindi Mental Status Examination(HMSE) and culturally adapted COGNITO test battery(Computerized assessment of adult information processing). The domain‐specific (attention, memory, language, visuospatial) cognitive scores were standardized and a composite score was calculated from the weighted averages of the individual test scores. General linear model was used to assess the association between the malnutrition indices and cognitive performance, adjusting for age, sex, education, tobacco, alcohol use, hypertension, diabetes, and depression. In a subset of participants who underwent 3T MRI(n = 1150), region of interest(ROI)‐based analysis was done to study the association between the malnutrition indices and brain ROI volumes normalized for total intracranial volume, adjusting for age, sex, and education.ResultBased on MUAC, GNRI, PNI, and CONUT score, 8.8%, 9%, 15%, and 19% of the participants (mean age: 57.49±9 years) were at a risk of malnutrition, respectively. GNRI had the best agreement with the SCI. We found a positive association between GNRI, BMI, MUAC scores and cognitive performance (Table‐1) and ROI brain volumes (Table‐2). MUAC had a stronger relationship to cognitive domains than BMI. No association was observed between PNI and CONUT scores and any of the outcome variables.ConclusionGNRI, a multivariable malnutrition index is a reliable predictor of cognitive performance and brain morphology. Additionally, MUAC, a simple and cost‐effective anthropometric measure, could be a potential indicator of rural Indians at risk of cognitive impairment.

Background/Objectives: Basal cell carcinoma (BCC) is the most frequent skin cancer in Caucasian populations. While dermoscopy supports diagnosis, accurate subtype classification requires histopathology. Line-field confocal optical coherence tomography (LC-OCT) offers high resolution, adequate penetration, and three-dimensional imaging, bridging the gap between dermoscopy and histopathology. This study assessed the concordance between LC-OCT and histopathology for BCC criteria and subtypes. Methods: We retrospectively analyzed 127 histopathologically confirmed BCCs from the Departments of Dermatology and Pathology, Hôpital Erasme, Brussels. LC-OCT images and corresponding histopathological slides were evaluated. Objective analysis used a predefined checklist of LC-OCT criteria compared with histopathology. Subjective analysis consisted of independent side-by-side assessments of global resemblance by three observers with varying expertise. Concordance rates and κ statistics were calculated. Results: The objective analysis showed the highest concordance (≥80%) for lobules, blood vessels, bright cells, lobule location, and dermal-epidermal junction disruption. Intermediate concordance (50–80%) was found for hemispheric morphology, outer bright rim, stromal stretching, and parakeratosis. Inner dark rim and palisading showed low concordance (<50%). Subjective evaluations demonstrated strong resemblance between LC-OCT and histopathology (overall concordance 81.1%), ranging from 86.6% to 98.4% across observers. Interobserver agreement was slight overall (κ = 0.10, p = 0.02), with one moderate pairwise κ (0.41). Conclusions: LC-OCT demonstrates good concordance with histopathology for key diagnostic and subtype-discriminating BCC features. Despite variability in subtle criteria, the findings support LC-OCT as a clinically relevant tool for non-invasive diagnosis and management of BCC.

Nano vesicular approaches for the treatment of skin cancer.

This study aimed to explore the relationship between axial length and ciliary body length, along with the potential anatomical variability among different races. Based on this, a new positioning for sclera incision in pars plana vitrectomy for patients with axial length ≥ 28mm was proposed and evaluated for feasibility and safety. 83 Chinese patients were enrolled. Pre-operative subjective refraction and axial length were obtained. The ciliary body length was measured intraoperatively. Data of Caucasian population from a published paper are also reviewed and analyzed. From all the enrolled Chinese patients, we selected 7 patients with axial length ≥ 28mm and who needed vitrectomy for macular diseases. New technique was used to make scleral incisions, and they were followed up for at least 12 months. The temporal and nasal ciliary body length have significantly positive correlations with axial length (p < 0.001, r = 0.386; p = 0.001, r = 0.357). The range of temporal ciliary body length and nasal ciliary body length in Chinese with axial length ≥ 28mm are 5.5-10.5mm and 5.5-9.5mm. The mean, range, variance and standard deviations of ciliary body length in Chinese are greater than Caucasian with axial length ≥ 28mm (p = 0.00034; p = 0.04996). No surgical-related complications occurred in the 7 patients with adjusted incision sites. There is a significant positive correlation between axial length and ciliary body length in nasal and temporal quadrant. Compared to Caucasians, Chinese population with axial length ≥ 28mm exhibit higher variability in the nasal and temporal ciliary body length. Therefore, positioning the scleral incision 2-3mm anterior to the ora serrata facilitates safer access of surgical instruments to the macular. This novel technique is not only simple but also offers improved cost-effectiveness. This study has been registered on the Chinese Clinical Trial Registry website, registration number: ChiCTR1800015732 (registration date: 17th April, 2018).

Cystic fibrosis is a common recessive disease in the Caucasian population. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause damage to the protein it encodes. Seven mutations are directly analyzed in Cuba, representing 55.5% of the pathogenic allelic variants in cystic fibrosis patients. The high allelic heterogeneity of this gene and its varied phenotypic expression make it vitally important to detect a greater number of genetic variants that cause the disease. With this data, patients can receive better genetic counseling and personalized treatment that would improve their quality of life. It is therefore necessary to search for new variants to complete the diagnosis. The objective of this work was to identify new genetic variants in the CFTR gene and confirm the clinical diagnosis of Cystic Fibrosis. Twenty-one patients clinically diagnosed as cystic fibrosis by the National Medical Genetics Network or identified as positive through the Neonatal Screening Program were analyzed. Eleven real-time polymerase chain reaction assays were performed on the isolated DNA, followed by high-resolution dissociation curve analysis. The amplification of these eleven fragments covered the five exons of the gene with the highest number of described mutations and the adjacent intronic regions. Subsequently, the samples that showed changes in the curve pattern were sequenced. Five mutations were detected: one pathogenic, two of uncertain significance, one benign, and one with conflicting clinical significance. Point genetic variants were identified in four of the five exons analyzed. The real-time polymerase chain reaction – high resolution melting curve technique proved useful for searching for point mutations along the CFTR gene sequence, which, in combination with Sanger sequencing, will allow for the identification of new variants in the Cuban population.

Background. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive tool for evaluating microvascular ab-normalities, increasingly explored in interstitial lung diseases (ILDs) with suspected autoimmune fea-tures. However, data on capillaroscopic patterns across ILD subtypes, especially in Caucasian popu-lations, are limited. Objectives: To compare NVC findings in patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), and connective tissue disease-associated ILD (CTD-ILD), and to assess correlations with autoantibody status—particularly myositis-specific antibodies (MSA – Jo-1, KS, PL7/PL12, NXP-2, MDA-5). Materials and Methods. Fifty-nine Caucasian ILD patients underwent NVC during routine evaluation. Based on multidiscipli-nary diagnosis, they were classified as IPF (n=9), IPAF (n=10), or CTD-ILD (n=40), further subdivided into systemic sclerosis (SSc, n=20) and non-SSc CTD-ILD (n=20). A validated 6-item semiquantitative scoring system (range 0–3 per item, max 18) was used; individual items are listed in Table 1. Clinical data included demographics and autoimmune serology (ANA, ENA, MSA). Statistical comparisons employed ANOVA and Student’s t-test. Results. Total capillaroscopic scores differed significantly across diagnostic groups: CTD-ILD (6.1±3.09), IPAF (4.6±3.31), and IPF (3.4±1.74) (p=0.0042). Within CTD-ILD, SSc patients showed higher scores than non-SSc (7.4±2.87 vs 4.8±3.22; p=0.0105). A four-group comparison confirmed this trend (p=0.0042). Among individual items, only “loss of capillaries” differed significantly across groups (p&lt;0.0001), with highest scores in SSc. Subsequently, the total capillaroscopic score was analyzed in relation to autoimmune serology: it was not significantly different between MSA+ and MSA- pati-ents (5.21±3.51 vs 5.51±3.17; p=0.7805). After excluding the 9 patients with IPF, the comparison between MSA+ and MSA- subjects still revealed no significant difference in total score (5.21±3.51 vs 5.95±3.25; p=0.5052). Conclusions. Nailfold videocapillaroscopy reveals distinct microvascular alterations among ILD subtypes, with sig-nificantly higher scores in CTD-ILD—particularly in SSc—compared to IPAF and IPF. While no signifi-cant differences emerged in relation to MSA, the observed gradient in capillaroscopic severity across autoimmune categories underscores the potential value of NVC as a complementary tool in the early diagnostic workup of ILD, especially in identifying autoimmune-driven forms and possibly refining IPAF classification. These findings support the integration of capillaroscopy into multidiscip-linary ILD assessment, where it may assist in detecting early autoimmune features and guiding im-munological testing. Moreover, expanding the cohort in future studies may help uncover more ro-bust associations between NVC findings and specific autoantibody subsets, particularly MSA.

BackgroundCD4⁺ T cell responses are key to adaptive immunity, yet the mechanisms underlying peptide selection and immunodominance across MHC class II variants in humans remain poorly defined. Two non-mutually exclusive models — First Bind-then cut (FBtc) and First Cut-then bind (FCtb) — have been proposed to explain immunodominant peptide selection, but experimental evidence in humans is mostly limited to a single allotype (HLA-DRB1*01:01).MethodsTo generalize processing mechanisms across DRB1 alleles we developed an integrative strategy combining in silico prediction and a reconstituted antigen processing system. The independent and combined outcome of both approaches was validated on curated SARS-CoV-2 epitope data (IEDB) for responses to the Spike and Nucleocapsid proteins across a panel of 11 DRB1 allotypes, covering over 90% of European Caucasian populations. Potential immunogenic regions identified by the combination of both methods enabled the design of minimalistic peptide pools whose performance was validated via flow cytometry and ELISpot assays in post-Covid19 and pre-pandemic donors. Mechanistic insights for the selection of immunodominant peptides were derived analyzing biophysical parameters and proteolysis of the model antigens.ResultsThree prediction tools used showed limited concordance for some allotypes (< 5%), but their combined output for all allotypes considered revealed potential immunogenic hotspots in the model antigens. Complementary, the reconstituted in vitro system identified allotype-dependent and promiscuous peptide candidates. Minimal peptide pools designed from the overlap of both methods featured improved performance to identify IEDB entries and induced robust CD4⁺ T cell activation in post-COVID-19 donors. Mechanistic modeling classified most immunodominant peptides from the Spike protein as arising via FCtb while FBtc predominated for Nucleocapsid. Epitope selection pathways are therefore antigen-dependent defined by proteolytic resistance and solvent accessibility.ConclusionsWe establish a scalable, genomics-informed framework for decoding CD4⁺ T cell immunodominance across diverse HLA contexts. Our findings reveal that antigen-intrinsic features govern the preferential processing pathway — FCtb for Spike and FBtc for Nucleocapsid — and validate the utility of minimal peptide pools for population-level immune-monitoring. These insights inform the design of personalized immunotherapies and broadly effective vaccines.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13073-025-01577-8.

The T allele variant of TERT rs2736098 has been associated with an increased risk of lung cancer (LC), yet various studies have yielded inconsistent findings. The purpose of this study is to verify the association between the rs2736098 variant and LC risk, as well as to investigate the differences in this association across different ethnic groups (Caucasians and Asians), various LC subtypes, and distinct smoking statuses. A computer search was conducted for literatures published up to December 20, 2024, in PubMed, Embase, Web of Science, and MEDLINE databases. Data were analyzed using RevMan 5.3, while sensitivity analysis and publication bias were assessed using Stata 14.0. The stability of the results was evaluated with TSA software Registration number: CRD420251030755. The T allele variant of rs2736098 was associated with an increased risk of LC ([OR] = 1.22, 95%CI [1.18, 1.27]), and this association was observed in both Caucasians ([OR] = 1.17, 95%CI [1.14, 1.20]) and Asians ([OR] = 1.26, 95%CI [1.19, 1.34]), with a stronger association in Asians than in Caucasians (Subgroup differences: P = 0.03, I2 = 79.7%). In specific LC subtypes, rs2736098[T] was linked to the risk of NSCLC and LUAD in both Caucasians and Asians (P < 0.05), and the strength of the association with NSCLC and LUAD was greater in Asians than in Caucasians (Subgroup differences: P < 0.05, I2 > 50%). Additionally, rs2736098[T] was associated with the risk of SCLC and LUSC in Asians (P < 0.05), with a similar strength of association for NSCLC and SCLC (subgroup differences: P = 0.87, I2 = 0%), but a stronger association for LUAD than for LUSC (subgroup differences: P = 0.01, I2 = 84.7%). The rs2736098[T] variant was also associated with the risk of LC in both Caucasian smokers/non-smokers and Asian smokers/non-smokers (P < 0.05), and the strength of the association did not vary between Caucasian smokers/non-smokers and Asian smokers/non-smokers (P ≥ 0.05, Subgroup differences: I2 < 50%). Within LC subtypes, rs2736098[T] was primarily associated with the risk of NSCLC in Asian smokers ([OR] = 1.59, 95%CI[1.19, 2.12]) and the risk of LUAD in Asian non-smokers ([OR] = 1.43, 95%CI[1.17, 1.75]). The T allele variant of rs2736098 is associated with LC risk, and Asians have a higher risk of LC, NSCLC and LUAD due to the rs2736098 variant compared to Caucasians. Therefore, there is a difference in the strength of the association between the two populations for LC risk due to the rs2736098 variant. Additionally, regardless of whether Caucasians or Asians are smokers, they are likely to be at risk for LC due to the variant in rs2736098.

To compare long-term structural disease progression in type 2 macular telangiectasia (MacTel) between Indian and Caucasian populations using a novel optical coherence tomography-based staging system structured around retinal layer involvement. This retrospective, observational, dual-center cohort study included 49 eyes from 30 Caucasian and 109 eyes from 55 Indian patients with type 2 MacTel. All patients had a minimum of 5 years follow-up. Disease severity was staged as early, intermediate, or advanced based on predefined OCT features involving the inner retina, outer retina, and presence of neovascularization. Progression was defined as a shift to a higher stage. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate progression and associated risk factors. At baseline, both groups had similar stage distributions (p = 0.451). Over the follow-up period, 82% of Caucasian and 81% of Indian eyes showed no disease progression. Median time to progress from early to intermediate stage was 32 months in Caucasians and 36 months in Indians (p = 0.847). Progression to advanced stage occurred after 51 and 69.5 months, respectively (p = 0.497). Survival analysis showed no significant differences in progression based on gender, ethnicity, or diabetes mellitus status. Structural progression in type 2 MacTel is slow and comparable across Caucasian and Indian cohorts over long-term follow up. Further studies to compare the influence of systemic and environmental conditions across different ethnicities will help understand pathogenesis of MacTel.