Search Results (3,109)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with ectopic fat accumulation and alterations in adipose tissue function. However, the relationships of structural and thermogenic adipose imaging markers with hepatic steatosis remain incompletely understood. This study aimed to jointly evaluate the cross-sectional associations of epicardial adipose tissue (EAT) thickness and infrared thermography (IRT)-derived brown adipose tissue (BAT)-related thermogenic activity with controlled attenuation parameter (CAP)-defined hepatic steatosis severity in adults with suspected MASLD. Methods: In this cross-sectional study, 207 adults undergoing clinical evaluation for suspected MASLD underwent transient elastography to obtain the controlled attenuation parameter (CAP) for hepatic steatosis assessment. EAT thickness was measured by transthoracic echocardiography, and BAT-related thermogenic activity was assessed by infrared thermography using the supraclavicular-to-chest temperature difference (ΔTemp). Associations of these adipose imaging phenotypes with CAP were evaluated using correlation analyses, sequential multivariable linear regression models, and BAT-stratified analyses. Results: EAT thickness increased progressively across CAP-defined steatosis grades (p < 0.001) and was positively correlated with CAP (r = 0.637, p < 0.001), whereas ΔTemp decreased with increasing steatosis severity and was inversely correlated with CAP (ρ = −0.277, p < 0.001). In sequential multivariable regression models, EAT thickness remained independently associated with CAP across adjustments for age, sex, body mass index, metabolic variables, and ΔTemp (standardized β = 0.559–0.623; all p < 0.001). Both EAT thickness and ΔTemp were independently associated with CAP in the fully adjusted model, with a stronger association for EAT thickness (standardized β = 0.559 vs. −0.167; p < 0.001 and p = 0.004, respectively). Stratified analyses demonstrated consistent associations between EAT thickness and CAP across both BAT-low and BAT-high activity groups. Conclusions: Greater EAT thickness and lower IRT-derived ΔTemp were independently associated with greater CAP-defined hepatic steatosis severity, with EAT thickness showing the stronger standardized association. These complementary structural and thermogenic imaging correlates warrant prospective evaluation to clarify their directionality and clinical relevance. Full article

Pedestrian-induced vibration is a critical serviceability concern for flexible structures such as footbridges and long-span floors. Existing human–structure interaction models commonly rely on single-degree-of-freedom simplifications and time-domain simulations, making them less suitable for frequency-domain analysis. This paper proposes a spectral analysis model for crowd-structure interaction vibration under unrestricted pedestrian traffic. The structure was formulated as a multi-degree-of-freedom modal system, whereas each pedestrian is represented by an independent spring–mass–damper system. To address the time-varying nature of moving crowds, a piecewise stationary assumption was introduced: the continuous walking path was discretized into fixed position groups, within each of which a time-invariant coupled equation of motion was established. The response spectra obtained for different position groups were combined using residence-time weighting, thereby allowing nonuniform walking speeds to be considered. The corresponding frequency response function was derived using the state–space method, and the structural acceleration power spectral density and root mean square responses were obtained by incorporating an unrestricted crowd walking load spectral model. Comparisons with field measurements from two footbridges demonstrated reasonable agreement. The resulting framework offers an efficient frequency-domain approach for vibration serviceability assessment under unrestricted pedestrian traffic. Full article

The rapid development of large model-driven agent applications, such as digital assistants and robots, requires 6G radio access networks (RAN) to deliver enhanced flexibility, adaptability, and low-latency capabilities. However, the existing RAN user plane (UP) architecture suffers from coarse decoupling granularity and significant cross-layer functional redundancy. These limitations severely hinder the on-demand orchestration and dynamic reconfiguration required by heterogeneous agent services. To address these challenges, this paper proposes a ComBERT-driven service-based RAN UP decoupling method, specifically targeting the functional coupling and redundancy between the PDCP and RLC sublayers. First, we develop a domain-specific language model, ComBERT, by pre-training a BERT model on a 3GPP protocol corpus and fine-tuning it on text-matching tasks to deeply comprehend protocol semantics. Subsequently, ComBERT is utilized to extract semantic features from UP functional components, employing a sliding window mechanism to overcome truncation in lengthy protocol texts and using cosine similarity to measure functional relevance. Finally, a threshold-based fusion algorithm is designed to identify and merge cross-layer redundant functions, thereby forming independent service units with distinct responsibilities. These fused units serve as the basic building blocks for scenario-specific orchestration. Simulation results demonstrate that the proposed method reduces the number of UP components by 12.5%, 18.7%, and 18.2% in eMBB, URLLC, and mMTC scenarios, respectively. Simultaneously, it decreases average processing delays by 7.9%, 10.2%, and 11.0% across these respective scenarios. Ultimately, this approach effectively improves the lightweight deployment, processing efficiency, and reconfiguration capabilities of the service-based UP, providing a crucial foundation for on-demand service orchestration in 6G networks tailored to agent services. Full article

Background/Objectives: To evaluate classification of improvement and agreement of walking-ability improvement criteria derived from outcome measures of walking capacity and performance among inpatients with spinal cord injury (SCI). Methods: Retrospective analysis of admission and discharge data from adults with SCI in the single-centre database from years 2020 to 2023: Six-minute Walk Test (6MWT), Ten-metre Walk Test (10MWT), Walking Index for Spinal Cord Injury; selected items of Spinal Cord Independence Measure (SCIM-III), and Functional Independence Measure; Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) Walking Mobility subscale. Twenty-three criteria for assessing walking-ability improvement including distribution-based change threshold (DBCT) and provisional milestones for in-home or in-the-community walking (derived from stroke population) and/or related independence were evaluated. Proportion of patients who progressed according to each criterion and agreement between criteria were calculated. Results: Data from 281 individuals were analysed (median 2 months since SCI). Improvement in SCIM-III Mobility Categories was achieved in 47%. Estimated DBCT of 6MWT (69 m) was exceeded in 46%, and DBCT of 10MWT at comfortable speed (CS) in 42% of participants. Forty-two percent of participants improved in provisional Walking Ability Categories (WACs) based on 6MWT or 10MWT_CS, 39% on SCIM-III-Stairs criterion, and 36% on the SCI-FAI criterion. Conclusions: The estimated DBCT and the WACs for 6MWT and 10MWT_CS are promising criteria to assess improvement in walking capacity after rehabilitation in patients with SCI; however, they require prospective validation against patient-centred and real-world mobility anchors. SCIM-III Mobility Categories and Stairs are recommended for assessing improvement in walking-related independence, and the SCI-FAI criterion for walking performance in everyday life. Full article

Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a focus on its role in inherited retinal dystrophies (IRDs) such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). FST has emerged as a key functional outcome measure in clinical trials, particularly in evaluating novel gene therapies for IRDs. Its fixation-independent nature and ability to detect residual visual function make it valuable for assessing disease progression and treatment efficacy. However, challenges remain regarding standardization and test variability. Ongoing efforts seek to standardize and optimize FST protocols and establish it as a standardized metric in both clinical and research settings. Full article

Psychological capital (PsyCap), comprising optimism, hope, self-efficacy, and resilience, is an important positive psychological resource associated with well-being and adaptive functioning. The present study aimed to evaluate the psychometric properties of the Lithuanian version of the revised Compound Psychological Capital Scale (CPC-12R) and to examine its associations with nature exposure and physical activity. A cross-sectional survey was conducted among 1255 Lithuanian adults aged 18–70 years (mean age 39.51 ± 13.84 years), and 64.4% were women. The total sample was randomly divided into exploratory (n = 628) and confirmatory factor analysis (n = 627) subsamples. Exploratory factor analysis supported a two-factor structure separating optimism from the remaining CPC-12R dimensions, whereas confirmatory factor analysis supported the theoretically expected second-order model comprising optimism, hope, self-efficacy, and resilience as first-order factors reflected by a higher-order PsyCap construct. The second-order model demonstrated good fit (robust CFI = 0.963, robust TLI = 0.952, robust RMSEA = 0.074, SRMR = 0.042) and strict measurement invariance across gender and place-of residence groups. Internal consistency was satisfactory to good for all subscales (McDonald’s ω = 0.79–0.85) and excellent for the total scale (ω = 0.93). Evidence of convergent validity was demonstrated through positive associations with self-esteem and life satisfaction and negative associations with psychological distress and poorer mental health. Furthermore, PsyCap explained a small but significant proportion of additional variance in mental health difficulties beyond self-esteem, life satisfaction, and psychological distress. PsyCap was positively associated with nature exposure, physical activity in nature, and leisure-time exercise. Hierarchical regression analyses indicated that greater nature exposure and more frequent physical activity in nature were independently positively associated with PsyCap after accounting for sociodemographic characteristics, whereas leisure-time exercise was not. Overall, the findings support the reliability and validity of the Lithuanian CPC-12R, particularly its total score, although the EFA results suggest caution when interpreting the four subscale scores separately. The cross-sectional findings further identify engagement with natural environments as a meaningful behavioural correlate of PsyCap. Full article

This paper addresses the problem of formulating generalized, non-extensive information-theoretic measures on finite non-distributive algebraic structures equipped with Riečan states, with particular emphasis on product Sheffer stroke basic algebras. Our approach formalizes finite summations, admissible partitions, refinement relations, and Sheffer stroke joint refinement candidates by using the primitive Sheffer stroke operation, with partition and marginalization properties imposed under the stated product and admissibility assumptions. By leveraging the state-theoretic properties of Riečan states, we construct baseline Shannon and logical entropies alongside algorithmic procedures for their computational evaluation. As the main result, we introduce and analytically characterize a parametric Tsallis entropy functional over these basic algebras. We prove its fundamental properties, including bounding inequalities, state concavity, monotonicity under refinement, subadditivity (for $\alpha >1$), conditional chain-type identities under the relevant joint refinement marginalization assumptions, and exact analytical convergence to the classical Shannon limit as the entropic index $\alpha \to 1$. Furthermore, under a state-dependent statistical independence condition, we show that the joint Tsallis entropy satisfies a pseudo-additive relation. By defining the Tsallis mutual information and the associated pseudo-additive residual, we isolate the deviation of a joint Sheffer stroke refinement from the factorized model determined by its marginal Riečan-state distributions. This residual is intended as a state-dependent algebraic indicator of deviations from the factorized Tsallis pseudo-additive model; it is not claimed to be an operational contextuality witness, a contextuality inequality, an entanglement measure, or a physical implementation criterion. Full article

Background: Retinal microvascular assessment has emerged as a promising non-invasive approach for evaluating vascular health. Recent advances in retinal imaging technologies have enabled detailed characterization of retinal vascular structure and function, raising interest in their potential role as biomarkers of exercise-related vascular adaptation. This systematic review with narrative synthesis aimed to summarize current evidence regarding the relationship between exercise, physical fitness, and retinal microvascular biomarkers. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published from January 2021 to June 2026, followed by a supplementary update search to identify eligible publications available through 31 July 2026. Search terms combined retinal microvascular assessment techniques with terms related to exercise, physical activity, physical fitness, and exercise training. Following screening and eligibility assessment, 42 publications were included in the final qualitative synthesis, comprising 20 publications identified through the initial search and 22 additional publications identified through the supplementary update search. Several publications represented complementary analyses of the same or overlapping study cohorts and were therefore not considered independent replications. Results: The included studies comprised observational studies and exercise intervention trials involving healthy individuals and clinical populations. Retinal biomarkers assessed included vessel diameters, arteriovenous ratio (AVR), vessel density, perfusion density, foveal avascular zone (FAZ), retinal oxygen extraction, wall-to-lumen ratio (WLR), and choriocapillaris perfusion parameters. Several studies reported measurable acute and chronic retinal vascular responses to exercise, although the direction, magnitude, and clinical meaning of these changes varied according to population, exercise modality, imaging technique, and biomarker. Observational studies generally reported associations between higher physical activity or cardiorespiratory fitness and a more favorable retinal vascular profile, but causal interpretation remains limited. Conclusions: Retinal microvascular biomarkers appear sensitive to acute physiological stress and may reflect selected adaptations associated with longer-term exercise exposure. However, retinal responses are heterogeneous and biomarker-specific, and their biological and clinical significance remains incompletely established. Methodological heterogeneity, overlapping study cohorts, and the limited number of adequately powered randomized and longitudinal studies constrain causal interpretation and generalizability. Retinal vascular measures should therefore currently be regarded as candidate biomarkers and research tools rather than validated surrogate outcomes or routine clinical measures. Full article

Background/Objectives: Patients with prolonged disorder of consciousness (PDOC) who regained consciousness in intensive care for consciousness rehabilitation (ICCR) were referred to further brain rehabilitation (FBR). The current retrospective cohort study evaluated the functional and cognitive outcomes of FBR. Methods: We assessed outcomes in 258 PDOC patients during FBR and used multivariate regression analyses to examine the influence of demographic and clinical characteristics on outcomes. Results: During FBR, Functional Independence Measure (FIM) motor, cognitive, and total scores improved from 21 ± 11, 11 ± 10, and 32 ± 15 to 43 ± 26, 18 ± 7, and 61 ± 32, respectively (p < 0.001). Dynamic Lowenstein Occupational Therapy Cognitive Assessment (DLOTCA) total scores increased from 57 ± 29 to 82 ± 36, and the average 6-min-walk (6MW) distances improved from 295 to 374 m (p < 0.001). Higher discharge FIM and DLOTCA scores were associated with younger age, traumatic etiology of the brain injury, shorter time to regaining consciousness, and higher FIM and DLOTCA scores at admission to FBR (p < 0.05). Conclusions: We observed functional and cognitive improvement in the examined patients. The improvement was associated with factors that may mainly reflect the severity of brain damage. The findings support continuing rehabilitation before and after emerging from PDOC. Full article

Background/Objectives: Male hypogonadism affects 35–50% of men with type 2 diabetes mellitus (T2DM) and obesity. The relationship between testosterone deficiency and response to incretin-based therapies (GLP-1 and GIP receptor agonists) remains incompletely understood. This systematic literature review, conducted following PRISMA 2020 guidelines, examines whether male hypogonadism represents a risk factor for poor response to incretin therapy or, conversely, whether these agents offer therapeutic benefits for this population. Methods: A comprehensive systematic literature search was conducted on 31 December 2024, across PubMed/MEDLINE, Scopus, and Web of Science using three search domains: (1) hypogonadism and incretin therapy response; (2) testosterone deficiency and GLP-1/GIP receptor agonists; (3) incretin response and testosterone. Eligibility criteria included human studies (randomized controlled trials [RCTs], observational studies, cohort studies, cross-sectional studies, systematic reviews, and meta-analyses) in adult men reporting testosterone levels and/or incretin response. Animal studies, pediatric populations, case reports with n < 5, editorials, and letters without data were excluded. Study selection followed PRISMA 2020 guidelines with independent dual screening. Risk of bias was assessed using the Cochrane Risk-of-Bias 2.0 tool (ROB2) for RCTs, the Newcastle–Ottawa Scale (NOS) for observational studies, and AMSTAR-2 for systematic reviews and meta-analyses. Due to substantial heterogeneity in study designs, populations, interventions, and outcome measures, a meta-analysis was not feasible; therefore, a narrative synthesis was performed. Results: From 326 records identified, 29 studies were included after deduplication and screening (primary studies: 14; systematic reviews/meta-analyses: five; narrative reviews/expert opinion: 10). Risk-of-bias assessment revealed moderate-to-high overall risk: RCTs had small sample sizes (n = 12–42) and short follow-up (12–24 weeks), raising concerns about statistical power; observational studies were of fair-to-good quality (NOS 4–7 stars) but subject to confounding; and systematic reviews were of low-to-moderate confidence (AMSTAR-2). Primary evidence from RCTs and observational studies demonstrates that GLP-1 receptor agonists (GLP-1RAs)—particularly semaglutide and liraglutide—and the dual GIP/GLP-1 receptor agonist tirzepatide significantly increase total testosterone levels in men with obesity-related functional hypogonadism (mean increase 2.5–5.2 nmol/L). This effect is largely mediated by weight loss and improvement of insulin resistance rather than direct androgenic action. Evidence regarding whether baseline hypogonadism impairs glycemic or weight-loss response to incretin therapy is limited and indirect; no adequately powered comparative trials stratified by baseline testosterone status were identified. Conclusions: Incretin-based therapies, particularly GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide, appear to improve testosterone levels in men with obesity-related functional hypogonadism, an effect that is largely mediated by weight loss and improvement of insulin resistance rather than a direct androgenic action. However, direct comparative evidence between hypogonadal and eugonadal men regarding glycemic or weight-loss response to incretin therapy remains insufficient to draw firm conclusions. The hypothesis that male hypogonadism does not impair incretin therapy response is biologically plausible but is currently supported only by indirect evidence. Prospective, adequately powered trials stratified by baseline testosterone status are needed to resolve this question. Full article

Background and Objectives: Facial nerve palsy (FNP) remains a clinically relevant complication after vestibular schwannoma (VS) resection. Recovery trajectories vary according to the severity of neural injury and early postoperative facial function. This study aimed to characterize the temporal pattern of facial nerve recovery during the first postoperative year and to explore factors associated with favorable long-term function. Materials and Methods: We retrospectively analyzed 51 adult patients who developed FNP after VS surgery between 2020 and 2023. Facial nerve function was assessed using the House–Brackmann (HB) grading system and the Sunnybrook Facial Grading System (SBFGS) at discharge and at 1, 3, 6, and 12 months postoperatively. Longitudinal changes were analyzed using non-parametric repeated-measures methods with effect-size estimation. Favorable 12-month facial nerve function was defined as HB grade I–II. Given the limited number of unfavorable outcomes, associations with 12-month recovery were explored using parsimonious Firth-penalized logistic regression models. Results: At discharge, 45.1% of patients had HB II, 29.4% HB III–IV, and 25.5% HB V–VI. Facial function improved significantly during follow-up. Median SBFGS total score increased from 58.0 at discharge to 99.0 at 12 months (Friedman χ² = 118.78, df = 4, p < 0.001; Kendall’s W = 0.58), while HB grade also improved significantly (χ² = 107.48, df = 4, p < 0.001; W = 0.53). At 12 months, 37/51 patients (72.5%) achieved HB I–II and none remained in the HB V–VI category. Synkinesis, defined as an SBFGS synkinesis subscore > 0, was observed in 10/51 patients (19.6%) at 6 months and 19/51 (37.3%) at 12 months. HB grade and SBFGS score at discharge were strongly inversely correlated (Spearman ρ = −0.943, p < 0.001) and were therefore evaluated in separate models. After adjustment for age and tumor size, each one-grade increase in discharge HB was associated with lower odds of favorable 12-month function (OR 0.30, 95% CI 0.11–0.58; p < 0.001), whereas each 10-point increase in discharge SBFGS was associated with higher odds of favorable function (OR 1.90, 95% CI 1.32–3.53; p < 0.001). Conclusions: Facial nerve function showed substantial longitudinal improvement during the first year after VS surgery. Early postoperative facial function was independently associated with 12-month outcome in exploratory penalized regression analyses. Recovery may continue over several months, supporting prolonged functional surveillance, while the independent contribution of rehabilitation and the effect of nerve grafting require evaluation in larger prospective cohorts. Full article

Coronary slow flow (CSF) is delayed distal contrast transit on angiography without flow-limiting stenosis; disturbed sleep may impair vascular control through autonomic, endothelial, inflammatory, and metabolic pathways. We evaluated Pittsburgh Sleep Quality Index (PSQI)-based sleep quality in relation to TIMI frame count (TFC)-defined CSF. This cross-sectional study enrolled 307 adults with nonobstructive coronary arteries undergoing angiography for chest pain; PSQI referenced the preceding month, and CSF was defined by corrected TFC > 27 frames in any major vessel; 132 participants had CSF and 175 normal flow. Global PSQI score was higher in CSF (median 7.0 vs. 5.0) and poor sleep quality (score > 5) was more frequent (75.8% vs. 49.7%; both p < 0.001). The global score correlated with mean TFC overall but not within flow groups. Each PSQI point independently raised CSF odds, including after STOP-Bang adjustment, although discrimination was modest. Sleep latency and short duration raised CSF odds; poor efficiency did not. Poorer sleep quality was independently linked to this angiographic slow-flow phenotype, mainly differentiating flow categories rather than tracking frame-count burden. Because coronary microvascular function was not measured directly, these hypothesis-generating findings should prompt systematic sleep assessment and prospective studies integrating objective sleep measures with invasive coronary physiology. Full article

Background: The Falls Efficacy Scale-International (FES-I) is an assessment tool designed to measure the level of fear of falling in older adults. This scale was developed to evaluate how much an individual fears falling during various daily activities. The aim of the study was to assess the discriminatory power of FES-I to predict falls within 2 years. The secondary objective was to evaluate the relationship between FES-I and vascular status. Material and Methods: In this prospective study, 130 patients (mean age, 64.7 ± 14.6 years) with chronic kidney disease (CKD) were analyzed. Of these, 90 patients had nondialysis CKD: 15 had stage G3 (G3a, n = 5; G3b, n = 10), 38 had stage G4, and 37 had stage G5. The remaining 40 patients (30.7%) were prevalent patients receiving maintenance hemodialysis. The most frequent cause of CKD was hypertension and diabetes in 57 (43.8%) of patients. The Falls Efficacy Scale-International (FES-I) was used to assess fear of falling. The Charlson Comorbidity Index (CCI) was used to measure comorbidity, and the 10-year cardiovascular risk was assessed using a web-based calculator QRESEARCH Cardiovascular Risk Algorithm, version 3 (QRISK^®3), and hemodynamic parameters were measured using a Mobil-O-Graph monitor. Participants were followed for 2 years to assess the occurrence of falls. Results: During the two-year follow-up, 49 of 130 participants (37.7%) experienced at least one fall. FES-I demonstrated good discrimination for falls (AUC 0.836; bootstrap 95% CI, 0.760–0.903). In multivariable logistic regression adjusted for age, sex, dialysis status, comorbidity, and functional status, FES-I remained independently associated with falls (adjusted OR per 1-point increase, 1.145; 95% CI, 1.060–1.237; p < 0.001). Addition of FES-I to the basic clinical model increased the AUC from 0.826 to 0.874, although the difference was of borderline statistical significance in paired receiver operating characteristics (ROC) comparison (p = 0.053). The data-derived Youden-optimal threshold was 25 points; however, bootstrap analysis indicated threshold variability, and this cut-off should be considered exploratory. Conclusions: Higher FES-I scores were independently associated with falls during two-year follow-up and may provide additional prognostic information beyond selected clinical risk factors. FES-I may represent a candidate screening instrument for fall-risk assessment in CKD; however, the proposed cut-off (25 points) requires prospective external validation. Full article

Objectives: To determine whether the superior anatomical control achieved with a treat-and-extend (T&E) anti-VEGF regimen translates into better five-year visual outcomes than a pro re nata (PRN) regimen in treatment-naïve center-involving diabetic macular edema (CI-DME), and to characterize the anatomical–functional relationship. Methods: In this retrospective propensity-score–matched survivor cohort, one eye per patient was analyzed. One-to-one nearest-neighbor matching balanced 14 baseline covariates. Longitudinal best-corrected visual acuity (BCVA) and central subfield thickness (CST) were analyzed using linear mixed-effects models with matched-pair clustering. Absence of a clinically meaningful visual difference was evaluated using two one-sided tests (TOST) with a prespecified ±5-letter equivalence margin. The anatomical–functional relationship was assessed by segmented regression. Sensitivity analyses included inverse probability of treatment weighting, doubly robust estimation, inverse probability of censoring weighting, best-/worst-case imputation, interval-censored recurrence modeling, and E-value analysis. Results: Both regimens improved BCVA, with no clinically meaningful difference at five years (T&E +6.2 ± 14.6 vs. PRN +6.9 ± 14.0 letters; difference −0.7 letters; 90% CI, −2.4 to 1.0; TOST p < 0.001). T&E achieved greater CST reduction (−172.3 vs. −114.2 µm; difference −58.1 µm; p < 0.001), higher dry-macula rates (73.8% vs. 59.5%; p < 0.001), fewer recurrences (2.2 vs. 3.9; p < 0.001), and fewer monitoring-only visits (14.6 vs. 28.4; p < 0.001), but required 53% more injections (25.1 vs. 16.4; p < 0.001). Segmented regression identified a breakpoint at 148 µm CST reduction; additional thinning beyond this threshold was not associated with further visual improvement. Baseline BCVA, ellipsoid zone disruption, and diabetic retinopathy severity, but not treatment regimen, independently predicted five-year vision. Results were consistent across sensitivity analyses. Conclusions: Among patients completing five years of therapy, additional anatomical drying beyond an exploratory, cohort-specific breakpoint of approximately 150 µm CST reduction was not associated with further measurable visual gain in this observational cohort. Regimen selection should therefore reflect treatment burden, monitoring requirements, and patient preference rather than anticipated visual superiority. Because the cohort included only patients completing five years of follow-up, these findings apply to adherent patients and should not be generalized to unselected populations. Full article

The GLA IVS4+919G>A founder variant causes a late-onset, cardiac-predominant form of Fabry disease, yet the severity of cardiac remodeling varies markedly among affected men. We studied 167 unrelated male carriers. Genome-wide association analyses included 81 men aged ≥50 years for left ventricular hypertrophy (LVH; left ventricular mass index [LVMI] ≥ 51 g/m^2.7) and septal hypertrophy (interventricular septal thickness at end-diastole [IVSd] ≥ 1.2 cm), and 149 men with plasma globotriaosylsphingosine (lyso-Gb3) measurements. Genotyping was performed with the Axiom Genome-Wide TPM 2.0 Array. Mean LVMI increased from 34.6 ± 11.3 g/m^2.7 at 20–39 years to 75.1 ± 34.0 g/m^2.7 at ≥60 years, although substantial variability persisted within each age stratum. rs1435166 and rs2572260, located in the adjacent EGLN1/SPRTN region, showed identical associations with LVH (both p = 4.14 × 10⁻⁸) and concordant genotypes in all 81 participants (dosage r² = 1.00; D′ = 1.00), indicating a single regional association signal. The association remained evident in exact testing, Firth logistic regression, and an age-adjusted continuous-LVMI analysis yielded concordant results. In the age-adjusted analysis, each rs1435166 T allele was associated with a 12.8 g/m^2.7 lower LVMI. Two intergenic variants met the exploratory threshold for septal hypertrophy, whereas no variant reached genome-wide significance for lyso-Gb3. These findings support the hypothesis that inherited genetic background contributes to variation in cardiac remodeling severity among carriers of the same pathogenic GLA variant. Independent replication, regional fine-mapping, and functional validation are required. Full article