Friedreich's ataxia (FRDA) is an inherited neurodegenerative disorder characterized by progressive ataxia and multisystem manifestations resulting from involvement of the peripheral and central nervous systems. While regional atrophy is known to be associated with symptoms, functional network alterations may represent a critical pathological mechanism; however, their specific contribution to motor and cognitive impairment remains unclear. We combined T1-weighted anatomical MRI and resting-state functional MRI (rs-fMRI) in 37 individuals with FRDA and 41 age- and sex-matched healthy controls and explored how functional connectivity differences are related to atrophy, clinical severity and cognitive performance. Regional volumes were quantified using morphometry analyses, spontaneous rs-fMRI activity was assessed via amplitudes of low-frequency fluctuations, and functional co-activation was evaluated among regions showing structural and neuronal activity alterations. Volume reductions were most pronounced in the brainstem, cerebellar white matter, hemisphere of lobules VI, X, and thalamus. Functionally, individuals with FRDA showed decreased fronto-cerebellar connectivity alongside increased intracerebellar, thalamo-striatal, and hippocampal-cerebellar coupling. Infratentorial and thalamic volume loss correlated strongly with clinical disease severity, whereas reduced frontal co-activation with cerebellar lobules VI, Crus I and II was moderately associated with poorer motor and cognitive performance. In contrast, increased intracerebellar and hippocampal-cerebellar coupling was observed particularly in individuals with more advanced disease and was partly associated with better cognitive outcomes. These findings indicate widespread disruptions of long-range cerebro-cerebellar connectivity together with increased intraregional coupling and potential network reorganization, underscoring the importance of network-level mechanisms for understanding clinical heterogeneity in FRDA and guiding future prognostic and therapeutic studies.

Diabetes mellitus (DM) is increasingly recognised as a heterogeneous and dynamic disorder that extends beyond a simple dichotomy between type 1 and type 2 diabetes. While the traditional classification remains anchored in dominant pathogenetic mechanisms, it provides limited insight into disease severity, progression and complication risk, and offers little guidance for individualised prevention and treatment. Growing evidence of overlapping phenotypes, variable trajectories and divergent risks underscores the need for a complementary framework capable of integrating biological mechanisms with clinical evolution. We propose the Diabetes Severity Classification (DSC) as a multiaxial, stage-based framework that conceptualises DM as a dynamic continuum. The DSC integrates four interrelated axes-β-cell functional reserve, insulin resistance and metabolic flexibility, glycaemic control and complication burden-and organises disease evolution into five stages, ranging from predisposition to complication-dominant disease. Rather than replacing existing aetiological classifications, the DSC operates orthogonally-that is, independently but in parallel-to them, providing a structured approach to describe disease state, severity and trajectory across all forms of DM. By explicitly incorporating cardiovascular risk, metabolic heterogeneity and evolving complication burden, the DSC aims to improve clinical interpretability and risk stratification, particularly at earlier stages when preventive interventions may have the greatest impact. Conceptually aligned with established staging systems in other chronic diseases, such as the cardiovascular-kidney-metabolic framework, the DSC offers a standardised language to bridge pathophysiology and clinical decision-making, supporting a more individualised and prevention-oriented approach to diabetes care.

The association of systemic immune-inflammation index with Th17/Treg imbalance, disease severity (PASI), and quality of life (DLQI/PLSI) in patients with psoriasis vulgaris: A cross-sectional study.

The aim of this study was to analyze changes in hospital incidence cases and disease severity of autoantibody-associated autoimmune encephalitis (AE) during the COVID-19 pandemic compared with the prepandemic period. A retrospective multicenter study analyzed data from 24 centers within the German Network for Research on Autoimmune Encephalitis (GENERATE). Patients with a new diagnosis of definite antibody-positive autoimmune encephalitis from 2017 to 2022 were included and divided into prepandemic (2017-2019) and pandemic (2020-2022) periods. Among 392 patients, 227 were diagnosed before and 165 during the pandemic (mean 9.5 vs 6.9 per site, p = 0.04). A reduction was observed in cases with antibodies to neuronal surface antigens (174 vs 122 cases; mean 7.3 vs 5.1 per site, p = 0.02), while cases with antibodies against intracellular antigens remained stable (p = 0.40). No differences were observed in disease severity, age, or sex distribution between periods. This study provides clinical data on antibody-positive AE before and during the COVID-19 pandemic. The findings do not support the hypothesis that SARS-CoV-2 infection triggers autoantibody-associated AE or increases disease severity.

Multiple studies have assessed Health-Related Quality of Life (HRQoL) in children with urea cycle disorders (UCDs); investigations in adults with the same disorders are rarer. Understanding the variables that modify self-reported HRQoL has become increasingly important as novel treatments are developed, with clinically meaningful endpoints required to assess efficacy. This was an ambispective study of participants enrolled in the Longitudinal Study of Urea Cycle Disorders (NCT00237315) conducted by the Urea Cycle Disorders Consortium (UCDC). Inclusion criteria included age ≥ 18 years and at least one completion of one of five HRQoL patient-reported outcome measures (PROMs). A total of 144 participants met inclusion criteria. Covariates included age at last assessment, sex at birth, specific UCD subtype, symptomatic status, treatments, and disease severity. The enrollees' self-reported HRQoL T-scores were not significantly different from the normative population. Whereas participants categorized as asymptomatic differed from those categorized as symptomatic in terms of disease severity, age at last HRQoL, and full-scale IQ, overall HRQoL did not differ. A model including age, sex, specific UCD subtype, symptomatic status, and disease severity revealed that perceived cognitive function was related to specific UCD subtype, while Anxiety and Emotional and Behavioral Dyscontrol were associated with sex at birth. When post-liver transplant participants were excluded, the pattern of associations was unchanged. Among adults with UCDs, responses on HRQoL measures revealed no significant differences in HRQoL when compared to normative populations. Cognitive reserve did not moderate the impact of diagnosis or treatment. Additional work in understanding and measuring HRQoL in this population is required.

In this study, a previously optimized pneumatic spray delivery (PSD)-based solid set canopy delivery system (SSCDS) was compared with an airblast sprayer (grower control [GC]) for the delivery of fungicides in the management of powdery mildew (Erysiphe necator) in vineyards. For 2023 and 2024 growing seasons, spray coverage was quantified for each application date and treatment. Visual disease severity on clusters and leaves was assessed five times per season. The accumulated area under the disease progression curve (AUDPC) was developed from these ratings. Over two seasons, spray coverage for PSD-SSCDS treatment ranged from 16.7% to 32.7%, whereas GC achieved coverage between 39.9% and 62.9%. The average difference in maximum cluster and foliar disease severity between GC and PSD-SSCDS was 5.5% and 14.2%, respectively. Despite lower spray coverage in PSD-SSCDS, the accumulated AUDPC for cluster disease severity was similar to GC treatments in both growing seasons. However, foliar disease severity differed significantly, with GC showing less disease than PSD-SSCDS. These study findings indicate that optimal emitter selection is crucial for achieving enhanced spray performance and effective disease control using the PSD-SSCDS technology in vineyards. Both fungicide spray treatments effectively protected clusters from powdery mildew, indicating PSD-SSCDS as an emergent alternative spray technology. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

This study aimed to investigate peripheral retinal angiographic features using ultra-widefield fluorescein angiography (UW-FAG) in eyes with idiopathic epiretinal membrane (iERM), compare them with fellow unaffected eyes, and assess their association with disease severity. This retrospective study included 84 patients (168 eyes) with unilateral iERM. UW-FAG images were analyzed in both eyes, and peripheral angiographic findings were categorized as vascular-associated or nonvascular. The frequencies of these features were compared between iERM and fellow unaffected eyes. The iERM eyes were further classified as early (Stages 1-2) or advanced (Stages 3-4) according to optical coherence tomography grading. The mean age of patients was 65.1 ± 7.3 years, and 64.3% were female. Peripheral abnormalities were significantly more frequent in iERM eyes, including granular hyperfluorescence (39.3% vs. 15.5%, P < 0.001), late-phase leakage (89.3% vs. 56.0%, P < 0.001), and microaneurysms (60.7% vs. 31.0%, P < 0.001). Advanced-stage iERM eyes showed higher rates of late-phase leakage (53.8% vs. 23.8%, P < 0.001), microaneurysms (59.0% vs. 31.0%, P = 0.001), and granular hyperfluorescence (26.9% vs. 7.1%, P = 0.005). The iERM severity positively correlated with late-phase leakage (r = 0.32, P = 0.0008) and microaneurysms (r = 0.25, P = 0.007). Peripheral angiographic abnormalities are more prevalent in iERM eyes and correlate with disease severity. These findings suggest that iERM is not confined to the macula but may reflect broader retinal pathophysiology. UW-FAG serves as a valuable adjunctive tool in comprehensively evaluating eyes with iERM.

Lack of respiratory droplet transmission of two recent human influenza A(H5N1) viruses in female ferrets.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by irreversible airflow limitation that usually progresses over time. SNHG14 is upregulated in the tissues with acute lung injury, but its role in COPD remains unknown. This study focuses on investigating the levels of SNHG14 in COPD and its potential predictive value for COPD, along with the molecular pathway through which SNHG14 influences COPD. This study included 110 patients diagnosed with COPD and 110 healthy controls. The levels of SNHG14 in serum and cells were detected by RT-qPCR. The predictive role of SNHG14 for COPD was analyzed using ROC curve. The HBE cells were treated with cigarette smoke extracts (CSE) to simulate the pathological environment of COPD. The impact of SNHG14 on HBE cell proliferation was examined via CCK-8 assay, the concentrations of proinflammatory factors and airway remodeling proteins in HBE cells were detected by ELISA kits. SNHG14 was upregulated in the serum of COPD patients, and its high expression may predict the occurrence of COPD in the early stage. Additionally, SNHG14 was associated with the severity of disease and level of inflammation in patients. In HBE cells exposed to CSE, SNHG14 expression increased. Knockdown of SNHG14 enhanced HBE cell proliferation and reduced inflammatory factors and airway remodeling proteins by modulating the miR-150-5p/BASP1 axis. Therefore, SNHG14 may serve as a diagnostic biomarker for COPD and influence the disease progression of COPD by regulating the miR-150-5p/BASP1 axis.

Genotype-phenotype correlations and putative modifier genes in SYNGAP1 Encephalopathy.

Aluminum-copper layered double hydroxide-enabled electrochemiluminescence-multicolor dual-mode biosensor for heparin-binding protein detection in sepsis diagnosis.

Respiratory tract infections remain a major cause of morbidity, with a disproportionate burden in the Caribbean. We aimed to characterize the seasonality and burden of key respiratory viruses across the Caribbean region of the Kingdom of the Netherlands. We analysed virological detection data from 2018 to 2024 collected across all six islands. Seasonal patterns of rhinovirus, influenza virus, respiratory syncytial viruses (RSV) and human metapneumovirus (hMPV) were modelled using generalized additive models. Associations with climate, tourism, age, and disease severity were assessed. Rhinovirus was most frequently detected. Influenza peaked between November and March (P < 0.001), coinciding with periods of high tourism (e.g., Aruba: OR 8.72; 95% CI: 6.37-12.10). In contrast, RSV peaked between June and December (P < 0.001), closely aligning with the rainy season (e.g., Aruba: OR 6.42; 95% CI: 4.26-9.75). HMPV showed a distinct seasonal peak between November and December (P < 0.001), partially overlapping with both RSV and influenza circulation. Rhinovirus detection was significantly associated with increased disease severity, including oxygen therapy need (OR 2.78; 95% CI: 1.72-4.50) and respiratory distress (OR 2.26; 95% CI: 1.42-3.67). RSV seasonality in the Caribbean differs substantially from that observed in temperate regions such as Europe, indicating that prevention schedules developed for temperate climates may be systematically misaligned with local transmission dynamics. Our region-wide data offer insights to guide locally tailored prevention strategies and underscore the need for climate- and mobility-aware respiratory virus preparedness in tropical island regions.

Genetic insights into hypospadias in the Taiwanese population: A whole-exome sequencing study in a single center.

Evaluation of the relationship between clinical parameters and retinal microvascular structures in children with atopic dermatitis: An optical coherence tomography angiography study.

Identifying the factors that contribute to gait efficacy in people with Parkinson's disease.

FNDC4 modulates macrophage responses and suppresses NF-κB in sepsis-induced lung injury.

Epithelial barrier dysfunction is central to the pathogenesis of Allergic Rhinitis (AR), yet its molecular mechanisms remain unclear. S100A8 is implicated in epithelial barrier disruption, but its role in AR is not fully understood. This study aimed to investigate S100A8 expression in AR and its association with barrier dysfunction. Nasal mucosal tissues were collected from 30 AR patients and 30 Healthy Controls (HCs). Expression levels of S100A8 and tight junction proteins (ZO-1, E-cadherin, occludin) were assessed by Immunofluorescence (IF), Western Blot (WB), and RT-qPCR. Correlation analysis was performed to evaluate the relationship between S100A8 and tight junction markers. Human Nasal Epithelial Cells (HNECs) from HCs were stimulated with House Dust Mite (HDM) extracts, and S100A8 expression was silenced using siRNA to assess its role in HDM-induced barrier disruption. WB and RT-qPCR results showed that the expression of S100A8 was significantly enhanced in nasal mucosal samples of AR patients compared to the HC group. S100A8 mRNA level was significantly elevated, and its level was positively correlated with the Visual Analog Scores (VAS) and total nasal symptom scores (TNSS) of the patients. Moreover, IF further confirmed that S100A8 was enhanced in the AR group, and mainly localised in the nasal epithelium. The expression of ZO-1, E-cadherin, and occludin was markedly reduced in AR patients and showed a negative correlation with S100A8 levels. In vitro, HDM stimulation of HNECs led to a dose- and time-dependent increase in S100A8 expression, along with reduced levels of tight junction proteins. Silencing S100A8 via siRNA significantly restored tight junction protein expression, indicating that S100A8 inhibition may help preserve nasal epithelial barrier integrity. S100A8 is upregulated in AR and associated with disease severity and epithelial barrier dysfunction. Targeting S100A8 may offer a therapeutic strategy to preserve nasal barrier integrity in AR. Level 3.

Motor Function Changes in Duchenne Muscular Dystrophy: A Case Series Using Conventional and Spinal Muscular Atrophy-Based Assessments During Viltolarsen Treatment.

Liver health issues in X-linked myotubular myopathy and centronuclear myopathies have historically been under-recognized, with liver monitoring not a routine focus of clinical care. Anecdotal case reports and liver-related adverse events in recent clinical trials highlight the growing need to better understand liver involvement in this population. A patient-led initiative brought together a multi-stakeholder expert working group, the 'Myotubular and Centronuclear Myopathy Global Liver Collaborative' who developed a liver health questionnaire to collect longitudinal patient-reported liver health data. Data from 219 participants was analysed and liver abnormalities were found to be most prevalent in myotubular myopathy patients with 36 % of affected males having abnormal liver function tests with liver issues also reported by symptomatic female carriers. Patients with liver abnormalities were also more likely to require invasive ventilation and had poorer motor function, suggesting a link between liver health and overall disease severity. Significant variation in liver monitoring was observed, with 30 % of participants never having undergone liver function blood tests demonstrating the need for routine liver screening to inform standards of care and guide clinical management. The patient-driven Liver Collaborative has been instrumental in raising awareness in liver related issues with clinical and patient communities.

Dietary naringenin alleviates experimental autoimmune encephalomyelitis in mice partially via estrogen receptor-mediated pathway.