Neurobiology of Learning and Memory

Objective Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation. Methods Twenty consecutive patients undergoing stereo-EEG in Marseille (2016-2018) were prospectively included. Continuous stereo-EEG recordings between two memory assessments (30 minutes and one week post-encoding) were analysed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-EEG analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal and combined: c-HipSZB) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. Associations were examined using univariate and multivariate analyses. Results Higher dominant-hemisphere hippocampal burden was associated with poorer one-week verbal memory (performance and retention), independently of most covariates. Higher c-HipSZB was associated with lower total recall performance (RT; free + cued) and RT retention ({beta} = -25.04 and -23.88; R2 = 0.57 and 0.53; p < 0.05) and accounted for the greatest variance in both outcomes (adjusted R2= 0.59 and 0.53; {beta} = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between non-dominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall. Interpretation Cumulative ictal-postictal hippocampal dysfunction is a major determinant of impaired long-term verbal memory consolidation in focal epilepsy.

Objective: Cognitive impairment is common among older adults with epilepsy, although efficient screening tools suitable for routine use are lacking. Here we examine, for the first time, the utility of the Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) as a screening tool to identify cognitive impairment in older adults with epilepsy. Methods: Participants included 83 adults (ages over 55) with epilepsy from the Brain, Aging, and Cognition in Epilepsy (BrACE) study and 83 age-, sex-, and education-matched cognitively healthy controls from the Alzheimers Disease Neuroimaging Initiative (ADNI-3). All completed the ADAS-Cog and a comprehensive neuropsychological battery to identify cognitive phenotypes (intact vs impaired). Performance on individual ADAS-Cog items and the total score was assessed, and diagnostic efficiency statistics were determined. Results: Epilepsy participants (mean age=66.4 years) performed significantly worse across the ADAS-Cog total score and 8 of the 13 individual test items compared to controls. The largest effect sizes were observed on verbal learning and memory tasks, particularly word recall (d=0.87) and delayed word recall (d=1.06). An ADAS-Cog total score of at or exceeding 15 yielded optimal diagnostic efficiency (67.5% accuracy, 68.8% sensitivity, 66.7% specificity) for identifying cognitive impairment. Significance: The ADAS-Cog is sensitive to detecting cognitive impairment in older adults with epilepsy and may represent a scalable screening option in this population. Additional comparative studies in older epilepsy populations are needed to determine the sensitivity of this measure to longitudinal change, cross-cultural applicability, and availability across languages. Plain language summary: Cognitive decline is common among older adults with epilepsy, although sufficient evidence supporting the use of screening tools to identify cognitive impairment in this population is lacking. The ADAS-Cog may be a useful screening option in epilepsy research and clinical care, although additional studies are needed to compare it with other cognitive screening tests and to confirm its applicability for clinical care and across cultures and healthcare settings.

We investigated whether people with Parkinson's disease who are dual GBA1+LRRK2 carriers have a milder, LRRK2-like phenotype as previously reported. This was accomplished by comparing clinical features and alpha-synuclein seed amplification assay (SAA) positivity rates between dual GBA1+LRRK2-PD(n=13), GBA1-PD(n=169) and LRRK2-PD(n=175) carriers in a cross-sectional retrospective study of Parkinson's Progression Markers Initiative (PPMI) data. Our results show that GBA1+LRRK2-PD rate(83%) is closer to GBA1-PD rate(87%) rather than LRRK2-PD rate (62%mp-value>0.05). GBA1+LRRK2-PD have both non-motor and motor phenotypic similarity of GBA1-PD(p-value>0.05). This small PPMI cohort indicates that dual GBA1+LRRK2-PD carriers' SAA positivity and phenotype are aligned with GBA1-PD.

Background Neuropsychiatric fluctuations in Parkinson's disease (PD) often accompany motor fluctuations, but their temporal relationship during the acute levodopa response remains unclear. Objectives To determine whether motor and neuropsychiatric responses occur synchronously during the OFF-to-ON transition. Methods Nineteen fluctuating PD patients underwent a high-resolution levodopa challenge with repeated assessments every 10 minutes for 60 minutes after levodopa administration. Motor symptoms (akinesia, rigidity) and neuropsychiatric fluctuations were quantified. Transition times (t25%-t50%-t75%-t100%) and response profiles were analyzed using correlation and clustering approaches. Results Motor and neuropsychiatric transition times were not correlated at any threshold (all FDR-corrected p>0.05; Bayes factors <1), supporting temporal dissociation. Among 18 patients with complete data, clustering revealed synchronous (6/18), neuropsychiatric-preceding (7/18), and motor-preceding (3/18) profiles. Conclusion Motor and neuropsychiatric responses to levodopa during PD fluctuations are partly independent and follow heterogeneous, patient-specific temporal profiles, supporting the search for distinct biomarkers and future individualized adaptative therapies

Background: Thalamic low-intensity transcranial focused ultrasound (tFUS) has shown promise for increasing behavioral responsiveness in disorders of consciousness (DOC), but no study has examined whether it can causally modulate the well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC impairment. Methods: Sixteen adult patients (44% Female; Age, M=37.81, SD=15.97) with a chronic DOC (Time Since Injury, M=3.39, SD=1.94 years) secondary to severe brain injury (TBI 44%, non-TBI 56%) underwent a 10-day inpatient, longitudinal, single-arm, open-label protocol. tFUS was delivered in a single session targeting the left central thalamus. Well-known behavioral (CRS-R), electrophysiological (EEG {delta}/{beta} ratio), metabolic (18F-FDG PET), and polysomnographic outcomes were assessed at baseline and after sonication. Results: The maximum CRS-R total score increased significantly following tFUS compared to baseline (M=13.27 vs. M=10.33; t(14)=7.407, p<0.001, d=1.913), as did the global EEG {delta}/{beta} ratio (N=14; W=17, p=0.025, r=0.68), with the degree of frontal slowing positively predicting behavioral gains ({tau}b=0.51, p=0.016). Glucose metabolism decreased bilaterally in thalamus and frontal, temporal, and parietal cortices at both post-tFUS timepoints compared to baseline. Finally, N2 sleep increased by 33% following tFUS (N=11; t(10)=2.386, p=0.038, d=0.72), though this did not survive correction. No severe adverse events were observed. Conclusion: Thalamic tFUS can causally modulate well-validated behavioral, electrophysiological, and metabolic biomarkers of DOC. The convergent inhibitory signature across these measures suggests a thalamocortical reset mechanism, complementing existing excitatory neuromodulation approaches and providing the mechanistic foundation for a large, randomized sham-controlled trial.

AIM: STXBP1-related disorder (STXBP1-RD) is a severe developmental and epileptic encephalopathy characterized by early-onset seizures and persistent cognitive and motor impairments. With disease-modifying trials emerging, a disorder-specific severity scale is needed. To address this, we adapted a validated clinician-reported measure from CDKL5 Deficiency Disorder to develop the STXBP1 Clinical Severity Assessment (S-CSA) and evaluated its psychometric properties. METHOD: The S-CSA was adapted from the CDKL5 Clinical Severity Assessment through expert consensus sessions with STXBP1 clinicians. Revisions addressed gaps in motor and vision domains, adding tremor and vision items. The measure was administered to 123 individuals with STXBP1-RD. Psychometric evaluation included confirmatory factor analysis, internal consistency, composite reliability, average variance extracted, and distinctiveness, compared with recommended thresholds. RESULTS: Analyses supported a three-domain structure (motor, communication, vision) with factor loadings >0.5 and strong internal consistency (Cronbachs alpha >0.7; composite reliability >0.88). Model fit and variance metrics met recommended standards, and domains demonstrated distinctiveness. No ceiling or floor effects were observed. Minimal skew was seen in motor (0.34) and communication (0.16) domains; positive skew in vision (2.2) was seen, identifying patients with and without cortical visual impairment. INTERPRETATION: The S-CSA demonstrates strong validity and reliability in STXBP1-RD and may show utility in clinical trials for STXBP1-RD and potentially other severe DEEs. Key Words: STXBP1-Related Disorder, Developmental and Epileptic Encephalopathies, Clinical Outcome Assessments

Background and Objectives In ADHD, a heterogeneous neurodevelopmental condition, behavioral and motor manifestations may reflect multiple inefficient or perturbed inhibitory systems. To evaluate Transcranial Magnetic Stimulation (TMS) evoked cortical silent period (CSP) duration, an indicator of GABA(B) receptor-mediated inhibition in motor cortex, as a potential biomarker of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. Method We retrospectively analyzed TMS data, obtained using both round and figure-of-8 coils, from three cross-sectional studies conducted in 8- to 12-year-old children with ADHD (n=79; 10.7 +/- 1.5 years old) and age-and-sex-matched typically developing controls (n=96; 10.5 +/- 1.4 years old). Results Median CSP was 32% shorter in ADHD (p=0.02). Regression analysis demonstrated a relationship between shorter CSP and both lower active motor thresholds (p < 0.0001) and more severe hyperactivity symptom rating (p = 0.026). Test-retest CSP measures in 83 children showed moderate reliability (intraclass correlation 0.77 [ADHD], 0.75 [controls]). Conclusion TMS-evoked CSP may be a useful biomarker in future investigations of ADHD subtypes, domains of impaired function, or treatment outcomes.

Background. Poor sleep quality is common in people with multiple sclerosis (pwMS) and reduces quality of life. Objectives. To examine associations between modifiable factors and sleep quality in pwMS. Methods. In a prospective clinic cohort (2017-2023), we evaluated whether baseline measures of disability, depression, fatigue, and pain were associated with poor sleep quality (Pittsburgh Sleep Quality Index, PSQI) cross-sectionally using covariate-adjusted linear regression, structural equation modeling (SEM), and LASSO logistic regression, and longitudinally using mixed-effects models. Results. In this cohort (n=750; mean age 48.9 years; 80.3% women, 88.7% relapsing type), higher body mass index ({beta} [95% CI]: 0.06 [0.01, 0.12], p=.001) and area deprivation index (6.78 [2.17, 11.39], p<.001) were associated with worse baseline PSQI scores. In adjusted analyses (n=730), disability, depression, fatigue, and pain were each associated with worse sleep. In SEM, pain had a moderate direct effect on sleep ({beta} [95% CI]: 0.56 [0.48, 0.64], p<.001). LASSO models that included pain outperformed the benchmark (AUROC 0.741 vs 0.517). Longitudinally (n=382), time and higher baseline pain predicted worse sleep ({beta} [95% CI]: time in months 0.04 [0.02, 0.06], p<.001; pain 0.36 [0.31, 0.41], p<.001). Conclusion. Pain is a key, potentially modifiable driver of poor sleep quality in pwMS.

Although the associations between cerebrovascular dysfunctions and Alzheimer's disease are increasingly appreciated, the relationship of cerebral blood flow and white matter hyperintensities with tau and amyloid-{beta} pathology remains unclear, particularly in the longitudinal context. This study investigated cross-sectional and longitudinal associations of cerebral blood flow and white matter hyperintensities with tau and amyloid-{beta} pathology using multimodal imaging and blood biomarkers in 179 participants from the ADNI3 cohort. Participants underwent structural (T1-weighted, T2-weighted FLAIR) and arterial spin labelling perfusion MRI, tau and amyloid-{beta} PET, and plasma assay tests for amyloid-{beta} 42, amyloid-{beta} 40, and phosphorylated tau-217. Tau from PET was negatively associated with cerebral blood flow both cross-sectionally and longitudinally in the posterior brain, independent of amyloid-{beta} quantified from PET. Higher white matter hyperintensities volumes were associated with higher levels of tau and amyloid-{beta} at baseline, but the associations were significantly attenuated after further adjusting for amyloid-{beta} and tau, respectively. Plasma amyloid-{beta} 42/40 ratio was negatively associated with white matter hyperintensity volumes both cross-sectionally and longitudinally. In conclusion, tau pathology showed spatially specific associations with cerebral hypoperfusion, independent of amyloid-{beta}, particularly in posterior regions. The attenuation of associations of white matter hyperintensities with amyloid-{beta} and tau after adjustment may reflect shared disease-related variance rather than distinct independent effects. Keywords: Alzheimer's disease, Cerebral blood flow, White matter hyperintensities, Tau pathology, Amyloid-{beta}.

INTRODUCTION: Cognitive trajectories may clarify how type 2 diabetes (T2D) and impaired fasting glucose (IFG) relate to dementia risk, but longitudinal associations remain unclear, particularly in the context of stroke. METHODS: Data from 5,631 dementia- and stroke-free older adults (mean age 75 years) from 7 international population-based cohorts were analyzed. Linear mixed-effects models estimated cognitive trajectories during stroke-free and post-stroke follow-up. Glucose status was defined by fasting glucose and prior T2D diagnosis. RESULTS: Over 6.6 years of follow-up (4.5% with incident stroke), T2D was associated with lower baseline cognitive performance compared with normal fasting glucose (-0.14 SD, 95% CI -0.21 to -0.07), but not with faster cognitive decline during stroke-free or post-stroke follow-up. IFG was not associated with lower cognitive performance or faster decline. DISCUSSION: In older adults, T2D was associated with persistently lower cognitive performance but not faster decline, suggesting adverse cognitive effects may be established before late life.

We present a compact pump-and-probe mid-infrared Optothermal Spectrometer (OTHES) equipped with Spatial Probing and Autocorrection (SPAC) optimized for robust intravital application in humans. SPAC-OTHES facilitates alignment stability and spectral comparability across different measurement sessions involving different skin types. Contrary to state-of-the-art, SPAC-OTHES uses camera-based beam detection and an auto-calibration mechanism that enables ca. 73% better spectral reproducibility in intravital measurements in human volunteers than non-calibrated readouts. Moreover, SPAC-OTHES has the potential to lower the glucose quantification error, as demonstrated here in artificial skin phantoms, where an improvement of 52% compared to conventional diode-based detection was observed. The compactness of OTHES, combined with reliable SPAC-readout, has the potential to accelerate commercialization and broad application of biosensors based on mid-infrared spectroscopy.

Background: Antenatal care (ANC) utilization is critical for improving maternal and neonatal health outcomes. Despite the World Health Organization recommendation of at least eight ANC contacts during pregnancy and the implementation of free maternal healthcare policies in Ghana, significant geographic and socioeconomic disparities in ANC utilization persist. This study therefore assessed the spatial distribution and geographically varying determinants of ANC utilization among women in Ghana. Methods: A cross sectional analytical study was conducted using women data from the 2022 Ghana Demographic and Health Survey. The analysis included women aged 15 to 49 years with an index child younger than five years preceding the survey. Descriptive statistics were computed using Stata version 18, while spatial analyses were conducted in QGIS version 3.44. Global Morans I was used to assess spatial autocorrelation, whereas Local Morans I and Getis Ord Gi analyses identified spatial clusters, hotspots, and coldspots of ANC utilization. Ordinary Least Squares (OLS) regression and Geographically Weighted Regression (GWR) models were fitted to assess global and local determinants of ANC utilization. Results: Overall, only 26.0% of women achieved adequate ANC utilization, while 74.0% reported inadequate ANC attendance. Adequate ANC utilization was higher among women with higher education (42.0%) and those from the richest households (41.3%) compared with women without formal education (19.1%) and those from the poorest households (17.6%). Regional disparities were observed, with Western (48.8%), Eastern (48.0%), and Greater Accra (47.3%) regions recording the highest ANC utilization, whereas Savannah (24.7%), Northern (25.8%), and North East (26.8%) regions recorded the lowest utilization levels. Global Morans I demonstrated significant positive spatial autocorrelation (Morans I = 0.457, p = 0.044), indicating geographic clustering of ANC utilization across Ghana. Getis Ord Gi analysis identified significant coldspots within Northern, Savannah, and North East regions, while Central Region demonstrated significant hotspot clustering. OLS regression showed that maternal education (B = 0.284, p = 0.003) and household wealth (B = 0.191, p = 0.011) positively influenced ANC utilization, whereas distance to health facility negatively influenced utilization (B = -0.156, p = 0.019). The GWR model demonstrated improved explanatory performance (Adjusted R-squared = 0.71), confirming substantial spatial heterogeneity in ANC determinants across Ghana. Conclusion: Adequate ANC utilization in Ghana remains low and geographically unequal. Maternal education, household wealth, and geographic accessibility significantly influence ANC utilization, with pronounced disparities concentrated within Northern Ghana. Spatially targeted maternal health interventions aimed at improving education, reducing socioeconomic inequalities, and enhancing healthcare accessibility are required to improve equitable ANC utilization across Ghana.

Abstract Aims To examine which demographic groups nicotine pouch advertisers chose to target on social media, and which groups Meta's algorithms actually delivered the adverts to. Design Cross-sectional analysis of advert-level data from the Meta Ad Library. Setting Meta social media platforms (including Facebook and Instagram) in the UK. Cases A random sample of 741 nicotine pouch adverts shown in the 12 months up to December 2025, and a comparison sample of 1,125 general adverts. Analyses of reach were restricted to adverts eligible for all genders and adult ages (444 pouch adverts; 674 general). Measurements Outcomes were advertiser-set gender and age-group targeting criteria (i.e., groups eligible to be shown each advert) and estimated advert reach to each group (i.e., number of people who saw each advert). Male-to-female reach ratios within age groups, and reach ratios comparing age groups, were calculated per advert and summarised using geometric means. To assess whether patterns were pouch-specific, comparisons with general adverts were made using ratios of reach ratios (RRR). Findings Advertisers of nicotine pouches targeted a broad sample; most adverts (79.1%; 586/741) were eligible to be shown to all genders, the remainder were restricted to men only. All were restricted to adults (minimum age 18 years) and most (95.6%; 708/741) had no upper age limit. Despite this, of pouch adverts eligible to be shown to all adults, adverts were more likely to reach men, particularly among younger men. Among 18-24-year-olds, pouch adverts reached around ten times as many men as women (RR 10.0, 95% CI 8.7-11.5), compared with a slight skew towards women for general adverts (RR 0.81, 95% CI 0.71-0.94), corresponding to an RRR of 12.3 (95% CI 10.0-15.1). Pouch adverts also showed a skew in reach towards younger age groups. Relative to those aged 35-44 years, reach was higher among 18-24-year-olds for nicotine pouch adverts (RR 1.33, 95% CI 1.17-1.51) but much lower for general adverts (RR 0.19, 95% CI 0.17-0.21), corresponding to an RRR of 7.0 (95% CI 6.0-8.2). Conclusions Nicotine pouch adverts on social media are often eligible to be shown broadly to all demographic groups but are disproportionately delivered to young men.

Wearable digital health technologies may complement traditional gait assessments in amyotrophic lateral sclerosis (ALS) by sensitively capturing real-world mobility changes. In this study, we validated six digital gait metrics derived from ankle-worn sensors in a natural history cohort of 182 individuals with ALS. Investigated metrics correspond to various aspects of gait, including volume, speed, intensity, similarity, variability, and fragmentation. Longitudinal analyses showed significant declines in step count, peak cadence, stride intensity, and stride similarity, with increasing stride duration variability and walking fragmentation over 52 weeks. Many participants exhibited greater relative change in the gait metrics than the self-reported ALS Functional Rating Scale-Revised (ALSFRS-RSE). Stratified analyses revealed that digital metrics captured significant functional decline even in participants with stable walking scores on the ALSFRS-RSE. These findings support the potential utility of these metrics for disease monitoring in ALS clinical care and trials.

Background: The rising prices of cancer medicines have intensified concerns about treatment access and health system sustainability particularly in low- and middle-income settings. Systematic facility level evidence on what medicines is actually available, at what prices, and at what cost to patients remains scarce, constraining evidence-based policy reform. Methods: Using adapted WHO/Health action international methodology, we conducted a cross-sectional survey of 52 cancer medicines across five therapeutic classes at five health facilities in Kisumu County, Kenya. Availability was measured as the proportion of facilities stocking each medicine. Affordability was assessed using days' wages required for the lowest-paid government worker to purchase standard treatment regimens, calculated per one chemotherapy cycle and maximum possible cycles. Results: Overall medicine availability was 48.1%, with marked inter-facility variation. Affordability analysis revealed severe financial barriers. The breast cancer AC regimen required 19.6-47.4 days' wages per full course; cervical cancer cisplatin, 19.8-49.2 days' wages; colorectal FOLFOX, 80.0-303.6 days' wages; and prostate docetaxel reached 437 days' wages at the highest-cost facility. The Social Health Authority's (SHA) KES 550,000 annual ceiling adequately covered cytotoxic regimens for common cancers at competitive prices but was exceeded by 24-116% for HER2-positive breast cancer requiring trastuzumab, with further strain for recurrent cervical and metastatic prostate cancers. Conclusions: Cancer medicines in Kisumu County are inconsistently available and highly variable in price resulting in inequitable access. We call for urgent retail price markup regulation, expanded pooled procurement through KEMSA, inclusion of priority targeted therapies on the Kenya Essential Medicines List, and SHA benefit packages redesigned around full-course regimen costs.

Background: RNA sequencing (RNA-seq) is increasingly recognized as a complementary tool to DNA-based sequencing for improving the diagnostic yield in Mendelian disorders. However, how the diagnostic performance of RNA-seq varies across molecularly and phenotypically distinct patient subgroups remains poorly defined. This study aimed to evaluate and compare the diagnostic utility of RNA-seq across three stratified groups of patients with non-diagnostic exome sequencing. Methods: We performed RNA-seq on whole blood samples from 90 patients with suspected Mendelian disease in whom clinical exome or whole-exome sequencing had failed to establish a molecular diagnosis. Patients were prospectively stratified into three groups of 30: (i) patients with a candidate variant of uncertain significance (VUS) with predicted splicing impact (Group 1), (ii) patients with a specific clinical pre-diagnosis but no identified pathogenic variant (Group 2), and (iii) patients without a specific pre-diagnosis or candidate variant (Group 3). Aberrant splicing, gene expression outliers, and allele-specific expression were analyzed using multiple bioinformatic tools and compared against a GTEx-derived control cohort. Results: RNA-seq contributed to a molecular diagnosis in 29 of 88 evaluable patients (32.9%). Diagnostic yield differed substantially across groups: 82.8% (24/29) in Group 1, 6.9% (2/29) in Group 2, and 10% (3/30) in Group 3. In Group 1, RNA-seq enabled reclassification of candidate VUS through direct demonstration of aberrant splicing events. In Group 2, RNA-seq identified a somatic mosaic ACTB variant missed by exome sequencing and reclassified a previously deprioritized APPL1 VUS. In Group 3, a deep intronic pseudoexon-activating variant in IGBP1 was identified in two siblings with severe microcephaly, providing evidence for a candidate X-linked microcephaly gene, and a pathogenic RNU4-2 variant was detected in a patient with ReNU syndrome, a non-protein-coding gene not captured by standard exome sequencing. Conclusions: RNA-seq has the highest diagnostic utility when applied to evaluate candidate splice variants identified by prior DNA testing but also provides independent diagnostic value in patients without candidate variants. The systematic comparison across stratified patient groups supports the integration of RNA-seq into clinical genomic workflows and highlights the need for standardized analytic frameworks.

Introduction Obstructive lung diseases (OLDs) are responsible for high rates of illness and death worldwide. Inflammation, chronic airflow limitation, and bronchial remodeling occur in OLD and eventually result in the unique respiratory sounds. Despite its subjective and having low reproducibility, still traditional auscultation using a manual stethoscope is the main method used to identify the lung sounds. Nevertheless, the combination of recent advancements in digital stethoscopes and AI (Artificial Intelligence) has permitted the objective measurement of lung sounds. Nevertheless, there is a lack of standardized, region-specific databases for AI training and validation. Even though lung sound classification is an emerging aspect in research and telerehabilitation the lobar wise acoustic pattern is still novel due to lack of prevailing database to train AI models. Identifying this gap this study aims to develop an acoustic repository and analyze the data using segmental lung sounds from patients with OLDs and healthy controls through an electronic stethoscope. Methods and analysis This is a cross sectional observational study involving 120 participants (60 OLD patients and 60 healthy controls). Lobar wise acoustic signals will be captured using an electronic stethoscope in healthy and diseases population. The data will be analyzed using Audacity software for annotations and then it will be used for feature extraction and statistical analysis. The acoustic features extracted through Audacity, will include frequency, intensity, pitch, and root mean square (RMS) energy. Repeated measures ANOVA will be applied to compare mean sound intensities across lung segments while Pearson correlation will be used to assess associations with body composition parameters. The data will then be standardized for AI-based diagnostic applications. Ethics and dissemination The study is being reviewed from the Ethics Review Committee, Faculty of Medicine, University of Peradeniya (2025/EC/87) will be sought. Informed consent will be obtained in writing. The dissemination of results will take place through peer-reviewed publications and the creation of a public database containing lung sounds from the region.

Background and Objective: Access to real-world electronic health records (EHRs) remains limited by privacy, governance and annotation constraints, hindering the development of clinical natural language processing models. Realistic synthetic progress notes may provide EHR-like corpora that preserve clinically rigorous information on diagnoses, treatments, symptoms, imaging, laboratory findings and therapeutic trajectories without relying directly on sensitive patient records. This study evaluates whether large language models (LLMs) can generate realistic Spanish prostate cancer progress notes from published case reports, preserving clinical content, temporality and hospital-style conventions.

Background: Regular exercise is a highly effective yet underutilized strategy to reduce cardiometabolic disease burden. Whether brief structured exercise programs confer lasting cardiometabolic benefits remains unclear. The STRRIDE-Prediabetes Reunion study examined legacy effects of exercise training on cardiorespiratory fitness, body composition, and cardiometabolic health. Methods: Seventy-three participants (71.3 {+/-} 7.2 years; 64% women; 77% White) completed Reunion assessments ~11 years after completing one of four 6-month interventions differing in exercise amount, intensity, and inclusion of diet-induced weight loss. Linear mixed effects models evaluated longitudinal trajectories; secondary analyses examined baseline-adjusted associations among short-term intervention response and Reunion outcomes. Results: Abdominal adiposity improved across all groups from baseline to Reunion, with waist circumference decreasing ~3 cm over the follow-up period. In contrast, cardiorespiratory fitness and fat-free mass declined significantly. A significant group by time interaction was observed for total fat mass (p=0.01), with continued fat mass reductions observed in women randomized to high amount exercise. After baseline adjustment, greater short-term intervention response was associated with more favorable Reunion outcomes across fitness, body composition, and cardiometabolic domains; fat-free mass showed the strongest association ({beta}=0.84, p<0.0001). Conclusions: In older adults with prediabetes, the STRRIDE-Prediabetes interventions produced several legacy health effects persisting more than a decade later. Legacy effects differed by sex and exercise dose, and short-term intervention response relative to baseline was associated with long-term outcomes, supporting targeted exercise strategies to preserve cardiometabolic health and functional independence with aging.

People living with HIV (PLWH) are known to maintain a degree of immune deficiency despite efficient antiretroviral therapy and may exhibit diminished responses to vaccines. In this study, we assessed the immune response to SARS-CoV-2 infection and vaccines in two geographically distinct PLWH populations. PLWH and HIV-negative (HIV-) participants were recruited from Qu&bec City (QC), Canada, and Bobo-Dioulasso (BD), Burkina Faso, for two visits at 24-week intervals during the predominance of the Omicron variant, from May 2022 to September 2023. Blood samples were collected at each visit for the detection of antibodies against spike (anti-S) and nucleocapsid (anti-N) proteins of SARS-CoV-2 in platelet-free plasma. A total of 360 participants were enrolled. We detected anti-S antibodies in 99% of participants, indicating that nearly all had prior exposure to the SARS-CoV-2 spike antigen, either through vaccination or prior infection. Anti-S titers showed no difference between PLWH and HIV& participants in each location, while significantly higher titers were observed in participants from QC compared to BD. In contrast, anti-N antibodies, indicative of prior infection, were detected in 39% and 86% of the participants in QC and BD, respectively, suggesting that the virus circulated largely in the latter population. No difference in anti-N levels was observed between PLWH and HIV& participants in BD. However, participants in QC had significantly lower titers compared to HIV participants. Overall, this study shows that PLWH develop robust antibody responses to SARS-CoV-2 vaccination, comparable to those observed in HIV& participants. Significant geographic differences were observed in anti-S titers, irrespective of HIV status, with participants from QC displaying higher titers. In contrast, participants from BD had higher anti-N antibody prevalence and titers, reflecting more SARS-CoV-2 infections in BD than in QC. Finally, analysis of anti-S antibody titers against several circulating variants revealed significantly lower levels in unvaccinated participants and in those vaccinated with monovalent vaccines in BD. No significant difference was observed between monovalent and bivalent vaccines administered in QC. All authors have seen and approved the manuscript.