Search Results (176,489)

Background/Objectives: Our prior epigenome-wide association study (EWAS) on multiple sclerosis (MS) identified myeloid-associated methylation signatures and an association with enhancer regions. Here we compared differential DNA methylation across three central nervous system inflammatory disorders: MS, neuromyelitis optica (NMO), and neurologic post-acute sequelae of COVID-19 (neuro-PASC). Methods: Whole-blood DNA was profiled on Infinium MethylationEPIC arrays. Analyses included EWAS at the CpG level, differentially methylation region (DMR) analysis, and gene regulatory-element enrichment using Locus Overlap Analysis (LOLA). Limma linear models were adjusted for race, EPIC array version, age, sex, disease-modifying treatment class, and blood cell composition. Results: All three diseases were associated with broad CpG-level differential methylation. The most robust findings were disease-specific DMR signatures in gene regulatory regions. All three diseases shared Lamin B1-anchored chromatin states as an architectural genomic feature but differed in immune regulatory transcription factor binding sites (TFBS), RNA polymerase (Pol II) occupancy, and DNase accessibility. MS was enriched for TFBS in myeloid CEBPB and SPI1/PU.1 and lymphocyte-associated RUNX3, EBF1, and BATF. MS hypomethylated DMRs were concentrated at active enhancers and myeloid TFBS, suggestive of chronic myeloid activation. NMO showed the clearest promoter and B lymphocyte associated profile. Neuro-PASC was associated with hematopoietic DNase accessibility and TFBS for BATF and EBF1. Conclusions: These results suggest that DNA methylation in MS, NMO, and neuro-PASC differ meaningfully in regulatory architecture rather than conforming to a single shared disease-associated methylation model. A long-term goal is to develop immune therapies for newly recognized diseases such as neuro-PASC. Full article

Background: Tick-borne encephalitis (TBE) is an endemic neuroinfectious disease prevalent in parts of Europe and is often associated with persistent neurological and cognitive sequelae. The aim of this study was to evaluate the long-term outcomes and predictors of post-encephalitic sequelae in adult patients with TBE in Latvia. Methods: A retrospective cohort with prospective follow-up was used that included 105 adult patients hospitalized with laboratory-confirmed TBE between 2018 and 2024. The patients’ clinical and demographic data were extracted from medical records, and reassessments were performed ≥6 months after discharge using structured clinical and neurological evaluations for neurocognitive, subjective, and neurological sequelae. Disease severity was classified using the Mickienė and Bogovič criteria, and sequelae severity was defined according to the Bohr criteria for post-encephalitic syndrome (PES). Results: Sequelae were observed in 52/105 (49.5%) patients and were more frequent in meningoencephalitis than in meningitis cases (18/25 [72.0%] vs. 33/77 [42.9%]). The most common persistent symptoms were impaired concentration (33/52 [63.5%]), fatigue (29/52 [55.8%]), and sleep disturbances (21/52 [40.4%]). Neurological sequelae included tremor (23/52 [44.2%]), vertigo (11/52 [21.2%]), and hearing impairment (5/52 [9.8%]). According to the Bohr criteria, most of the patients had mild sequelae (42/52 [80.8%]), while 10/52 [19.2%] had moderate sequelae; no severe cases were observed. In the multivariable analysis, increasing age was independently associated with greater sequelae severity (OR = 1.045 per year; 95% CI, 1.015–1.073; p = 0.003). Sex, comorbidities, biphasic disease, and length of hospital stay were not significant predictors. Acute neurological manifestations, particularly paresis (p = 0.002) and tremor (p = 0.019), were associated with worse outcomes. Although the disease severity scores correlated with sequelae in unadjusted analyses, neither the Mickienė nor the Bogovič classification independently predicted outcomes after adjustment. Conclusions: Nearly half of the hospitalized patients with TBE included in this study developed long-term sequelae, which were predominantly neurocognitive and mild in severity. Age was the primary independent predictor of worse outcomes, while acute neurological deficits such as paresis and tremor also indicated increased risk. These findings highlight the substantial burden of post-encephalitic syndrome and the need for structured long-term follow-up in TBE survivors. Full article

Natural killer (NK) cells are crucial components of innate immunity and rapidly eliminate abnormal cells through ligand–receptor signaling without prior sensitization. Vitamin C is known to enhance NK cell function; however, its susceptibility to oxidation may limit its efficacy in NK cell activation. This study evaluated the efficacy of Aptamin C, a stabilized conjugate of vitamin C and an aptamer, in enhancing NK cell activation. In the in vivo randomized placebo-controlled study, 120 participants were randomized to receive either Aptamin C or placebo, and 109 participants were included in the final analysis. Participants received Aptamin C at a dose of 36.057 mg/day or placebo for 4 weeks. The results showed significant increases in NK cell cytotoxicity after 2 and 4 weeks in the Aptamin C group. Additionally, serum levels of cytokines and cytotoxic granules associated with NK cell activity peaked 4 weeks after Aptamin C intake. Subgroup analysis showed that the enhancing effect of Aptamin C on NK cell activity was mainly observed in participants older than 40 years, whereas no significant effects were detected in participants aged <40 years. In the in vitro study, NK-92 cells treated with Aptamin C were compared with NK-92 cells treated with vitamin C. Aptamin C treatment enhanced proliferation, survival, cytotoxicity, and cytotoxic granule production in NK-92 cells compared with vitamin C treatment. These findings indicate that Aptamin C may effectively promote NK cell activation, particularly in middle-aged and older adults, and suggest its potential as an immunomodulatory supplement for supporting NK cell function. Full article

Background: Health literacy plays an important role in medication understanding, self-management, and engagement with healthcare services among older adults. Limited health literacy may contribute to medication-related problems and reduced utilization of pharmacist-led services in geriatric populations. Methods: A cross-sectional, questionnaire-based survey was conducted among geriatric outpatients (≥60 years) attending a tertiary-care teaching hospital in Saudi Arabia. Health literacy was assessed using a four-domain functional tool—covering prescription label comprehension, understanding of healthcare instructions, confidence in completing medical forms, and comprehension of written health information—developed in alignment with established health literacy frameworks, including the Health Literacy Survey—European Union (HLS-EU) model and Baker’s conceptual framework. Participants were classified as having higher health literacy (0–2 domains impaired) or lower health literacy (3–4 domains impaired). Sociodemographic characteristics, clinical burden, medication self-management behaviors, and awareness of clinical pharmacist services were recorded. Multivariable logistic regression was used to identify factors independently associated with lower health literacy. Results: A total of 200 participants were included. Impairment in three or more domains was observed in 55.5% of participants. Lower health literacy was independently associated with older age, lower educational attainment, lower income, female sex, multimorbidity, and polypharmacy. Participants with lower health literacy reported higher rates of missed or incorrect medication dosing and unreported adverse drug reactions and lower use of medication management aids. Awareness of clinical pharmacist services and prior exposure to pharmacist counseling were significantly lower among participants with lower health literacy. Willingness to receive pharmacist counseling was higher among participants with higher health literacy and greater awareness of pharmacist roles. Conclusions: Health-literacy impairment is common among geriatric outpatients and is associated with medication self-management behaviors and engagement with pharmacist-led services. These findings highlight the relevance of functional health literacy in geriatric medication use and support further research on literacy-sensitive pharmacist-led interventions. Full article

Phosphate tailings (PTs), a solid waste generated from phosphate flotation, are a low-grade phosphate resource rich in quartz and dolomite. Their long-term accumulation leads to both resource loss and environmental risks, making valorization increasingly important for the sustainable development of the phosphorus chemical industry. In this study, calcareous–magnesian PTs were used as raw materials, and selective hydrothermal leaching with weakly acidic AlCl₃ solution was employed to separate the dolomite phase and directly construct a Ca-Mg-Al precursor solution for layered double hydroxides (LDHs). The LDHs were subsequently synthesized by co-precipitation and evaluated for phosphate removal from wastewater. The results showed that the precipitation pH markedly affected the phase composition and platelet morphology of the LDHs, while appropriate aging conditions further improved their adsorption performance. Under the optimal conditions of pH 12, aging at 40 °C for 2 h, the obtained LDHs exhibited the best phosphate uptake. Adsorption kinetics followed the pseudo-second-order model, and the maximum adsorption capacity calculated from the Langmuir model reached 38.61 mg-P/g. Characterization by XRD, FTIR, TG-DTA, point of zero charge, and XPS indicated that phosphate removal was dominated by surface complexation, accompanied by anion exchange, ionic precipitation, and electrostatic attraction. Full article

Gait refers to an individual’s unique walking pattern and is a promising biometric for age and gender estimation. Human gait exhibits inherent bilateral symmetry arising from the coordinated movement of the left and right sides of the body. However, occlusion remains a major challenge that disrupts the symmetric structure of gait patterns and degrades recognition performance. This paper investigates the impact of different occlusion types on gait-based age and gender estimation and proposes a Generative Adversarial Network (GAN)-based image restoration model to mitigate occlusion effects. Two occlusion types, namely block-wise and component-specific, are examined. A self-collected dataset of 715 side-walking gait energy images (GEIs) from 120 subjects was synthetically occluded to simulate real-life scenarios. Block-wise occlusion was applied both vertically and horizontally across GEI silhouettes, while component-specific occlusion targeted individual body parts. GAN-based restoration was subsequently applied to occluded images prior to model training. Experimental results confirm that occlusion significantly degrades recognition accuracy, with larger occluded regions causing greater performance drops. Shoulder occlusion most severely impacted age estimation, while head occlusion had the greatest effect on gender estimation. GAN-based restoration substantially recovered lost accuracy, demonstrating the potential of restoration techniques in compensating for missing body information. These findings highlight the importance of upper-body regions in gait-based soft biometrics and demonstrate the need to address occlusion in real-world gait recognition systems. Full article

Background/Objectives: Cervical radiculopathy is a frequent cause of pain, often leading to disability, reduced quality of life, and significant healthcare utilization. Cervical epidural steroid injections are widely used, though safety concerns have been reported. Ultrasound-guided cervical retrolaminar block (RLCB) is a potential alternative. The purpose of this study was to evaluate the long-term clinical trajectory after ultrasound-guided cervical retrolaminar block, including pain outcomes, patient-reported improvement, and the rate of subsequent cervical spine surgery. Methods: This is a retrospective cohort analysis that was conducted at the Pain and Spine Surgery units in a single center. : We included 121 patients with cervical radiculopathy treated between January 2020 and September 2022 (mean age 49.4 ± 11.1 years; 51.2% male). All patients underwent RLCB. s: Primary outcome measures were subsequent cervical decompressive surgery and composite pain response (≥2-point absolute and ≥50% relative NRS reduction). Secondary outcome measures included recurrence, analgesic use, global rating of change (GRC), satisfaction, willingness to repeat, and safety. Baseline data was extracted from records; structured follow-up interviews were conducted at two years. Results: At two years, 9.1% required surgery, and 57.9% achieved composite pain response; 74.4% reported ≥2-point NRS reduction. GRC scores showed improvement (mean 5.0 ± 3.4), with 37% reporting “very much better.” Satisfaction was high, with 70.2% willing to repeat. Pain recurred in 71.1% but persisted in 28.9%. No major complications occurred; minor events were reported in 6.6%. Outcomes were less favorable in patients with pre-injection pain duration ≥1 year. p. Conclusions: In this retrospective cohort, cervical RLCB was associated with sustained patient-reported improvement, high satisfaction, and a 9.1% observed subsequent surgery rate at two years. These findings are hypothesis-generating and require confirmation in prospective controlled studies. Full article

Background: Cerebral aneurysms and aneurysmal subarachnoid hemorrhage (aSAH) may induce cardiac electrical instability through autonomic dysregulation and an exaggerated neurohumoral stress response. Electrocardiographic (ECG) abnormalities, including QT/QTc prolongation, QTc dispersion, and P-wave dispersion, are recognized markers of ventricular repolarization heterogeneity and atrial conduction abnormalities associated with arrhythmogenic risk. However, data regarding the reversibility of these electrophysiological alterations following definitive aneurysm treatment remain limited. Methods: This retrospective, single-center study included 39 patients with cerebral aneurysms who underwent microsurgical clipping between January 2025 and May 2026 and 35 age- and sex-matched healthy controls. Standard 12-lead ECGs were evaluated at baseline (preoperative) and one month after surgery in the aneurysm group. QT interval, corrected QT (QTc) interval, QTc dispersion, and P-wave dispersion were assessed using standardized methods. Baseline transthoracic echocardiographic parameters, including left ventricular ejection fraction and left atrial diameter, were evaluated to minimize potential confounding related to structural cardiac abnormalities. Between-group and within-group comparisons were performed using appropriate statistical analyses. Results: Baseline demographic and echocardiographic characteristics were comparable between the aneurysm and control groups. Patients with cerebral aneurysms demonstrated significantly higher baseline QT interval, QTc interval, QTc dispersion, and P-wave dispersion compared with healthy controls. Following microsurgical treatment, significant reductions in QT interval, QTc interval, QTc dispersion, and P-wave dispersion were observed at one month compared with preoperative values, whereas PR interval and QRS duration remained unchanged. These findings suggest a partial normalization of cardiac electrical heterogeneity after definitive aneurysm treatment. Conclusions: Cerebral aneurysms are associated with increased ventricular repolarization and atrial conduction heterogeneity, reflecting autonomic-mediated cardiac electrical instability. The significant reduction in QTc dispersion and P-wave dispersion following microsurgical treatment suggests that these electrophysiological abnormalities may be at least partially reversible after aneurysm repair. ECG-derived markers such as QTc dispersion and P-wave dispersion may represent practical and non-invasive tools for monitoring cardiac electrical instability and recovery in patients with cerebral aneurysms. Full article

Global urbanization and population aging urgently require cities to adapt to support older adults’ independence and well-being. While active mobility drives health and social equity, micro-scale proximity remains under-studied. This study evaluates ‘hyper-accessibility’ to essential daily services for older adults in Madrid and Munich, examining distributive spatial justice and its implications for healthy aging. Using quantitative spatial analysis, walking accessibility to seven key services was modeled at a strict 300 m threshold. These metrics were intersected with a sociodemographic disadvantage score to reveal urban disparities. Key findings expose structural contrasts. In Madrid, 50.82% of older adults achieve hyper-accessibility to daily services, though green areas (8.86%) and health facilities (15.82%) represent critical gaps. Conversely, Munich’s decentralized fabric yields hyper-accessibility for just 31.6% of seniors, with community centers (7.19%) and sports facilities (8.6%) being severely restricted. These spatial inequities highlight how restrictive walking thresholds function as invisible barriers to active mobility, isolating older populations. Ultimately, integrating hyper-accessibility metrics into local planning is vital for mitigating these baseline deficits and fostering age-inclusive, socially just urban environments. Full article

Objective: Malignant middle cerebral artery infarction is associated with high mortality despite decompressive craniectomy. Reliable biomarkers predicting early outcome remain limited. The aim of this study was to evaluate the prognostic significance of inflammatory biomarkers, particularly the systemic immune–inflammation index (SII), for predicting in-hospital mortality in patients undergoing decompressive craniectomy for malignant middle cerebral artery infarction. Methods: This retrospective study included 31 patients who underwent decompressive craniectomy for malignant MCA infarction between 2014 and 2024. Demographic, clinical, radiological, and laboratory variables were analyzed. Results: Overall in-hospital mortality was 61.3%. Non-survivors had significantly higher SII, neutrophil count, neutrophil-to-lymphocyte ratio, serum creatinine, and higher prevalence of hypertension and anticoagulant therapy. ROC analysis showed that SII had the highest predictive performance (AUC = 0.833). Multivariate analysis identified age, serum creatinine, NLR, SII, hypertension, and anticoagulant therapy as independent predictors of mortality. Patients aged ≥65 years had significantly higher in-hospital mortality than younger patients. Conclusions: Elevated SII is a strong independent predictor of early mortality after decompressive craniectomy and may serve as a simple and clinically applicable biomarker for risk stratification. Full article

Electroencephalography (EEG) has emerged as a promising modality for biometric user authentication due to its inherent uniqueness and resistance to spoofing attacks. Significant advances in brain wave signal analysis over recent years have reinforced its potential as a distinctive and reliable biometric trait. However, a comprehensive evaluation of the overall progress in this field remains limited. To address this gap, this paper presents an in-depth survey of EEG-based user authentication systems. The survey begins with a comprehensive overview of the human brain’s structure and functional organization, followed by a discussion of EEG signal acquisition principles and commonly used recording devices. It provides a detailed review of data acquisition protocols, publicly and proprietary available EEG databases, and essential preprocessing techniques required for effective signal refinement. The paper further examines feature extraction strategies and classification algorithms employed in EEG-based biometric authentication. In addition to reviewing existing methodologies, the survey identifies key challenges and future considerations in EEG biometrics, such as signal variability, age, mental health conditions, inter-session and inter-subject variability, etc, to establish stable and robust algorithms. This work serves as a foundational reference for researchers, outlining current progress and presenting a structured roadmap for future advancements in EEG-based biometric systems. Full article

Objective: Patellofemoral pain syndrome (PFPS) is one of the most common causes of anterior knee pain and is associated with biomechanical, muscular, and functional impairments affecting the extensor mechanism of the knee. Quadriceps muscle dysfunction, altered tendon morphology, and impaired lower extremity biomechanics have been suggested to contribute to patellofemoral joint instability and pain development. The aim of this study was to evaluate the muscle and tendon thicknesses of the extensor mechanism using ultrasonography in individuals with PFPS and to investigate the relationship of these measurements with knee pain, knee function, and physical performance, with particular emphasis on the combined assessment of muscle morphology, tendon morphology, and functional performance parameters. Methods: This cross-sectional study was conducted between 5 November 2019 and 15 December 2019, including 80 individuals aged 18–45 years who presented with anterior knee pain and were clinically diagnosed with patellofemoral pain syndrome (PFPS). Demographic characteristics of the participants were collected. Pain severity was assessed using the Visual Analog Scale (VAS), and functional status was evaluated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Physical performance was assessed using the 6 m walk test and the five-repetition sit-to-stand test. Ultrasonographic examination was used to measure rectus femoris muscle thickness, vastus intermedius muscle thickness, quadriceps tendon thickness, and patellar tendon thickness using a high-frequency linear probe in a standardized supine position with the knee relaxed and the lower extremity muscles at rest. Results: The mean age of the participants was 32.11 ± 7.08 years, and the mean body mass index (BMI) was 25.05 ± 4.11 kg/m². Of the participants, 42 (52.5%) were male and 38 (47.5%) were female; 46 (57.5%) were smokers and 34 (42.5%) were non-smokers. Ultrasonographic measurements showed that rectus femoris muscle thickness was 1.98 ± 0.45 cm, vastus intermedius muscle thickness was 1.75 ± 0.53 cm, quadriceps tendon thickness was 0.54 ± 0.12 cm, and patellar tendon thickness was 0.35 ± 0.08 cm. Rectus femoris, vastus intermedius, and quadriceps tendon thicknesses were significantly higher in males compared to females (p = 0.001). Individuals with BMI > 25 had greater rectus femoris (p = 0.023) and vastus intermedius (p = 0.001) muscle thicknesses. A negative correlation was found between rectus femoris muscle thickness and WOMAC total (r = −0.227, p = 0.042) and WOMAC pain scores (r = −0.233, p = 0.028). Additionally, a significant relationship was observed between quadriceps tendon thickness and the five-repetition sit-to-stand test (r = −0.247, p = 0.044). Conclusions: In patients with PFPS, quadriceps muscle and tendon thicknesses were found to be associated with certain demographic and clinical parameters. Ultrasonographic evaluation of muscle and tendon structures may be a useful, non-invasive, dynamic, and radiation-free method for better understanding the clinical characteristics of PFPS and its relationship with physical performance. Ultrasonographic assessment may also provide complementary information for rehabilitation planning and functional evaluation in individuals with PFPS, although these findings should be interpreted cautiously because of the cross-sectional design and weak correlations observed. Full article

Background: Linear growth during childhood is a key indicator of health status and child development, and liquid cow’s milk has been proposed as a potentially relevant dietary component for this outcome. In this systematic review, we aimed to synthesize the available evidence on the association between liquid cow’s milk consumption and linear growth outcomes in infants and children aged 6 months to 12 years. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Observational and experimental studies published in peer-reviewed journals, with no language restrictions, were included if they assessed habitual liquid cow’s milk consumption as the main exposure and reported linear growth outcomes such as height, growth velocity, or height-for-age z-scores. Searches were performed in PubMed (MEDLINE) and Scopus from database inception to 15 January 2026. Study selection, data extraction, and risk-of-bias assessment were carried out systematically. Due to methodological heterogeneity among the included studies, results were synthesized narratively. Results: Twelve studies conducted across diverse geographic and socioeconomic contexts were included. Most studies reported positive associations between liquid cow’s milk consumption and indicators of linear growth, including greater height, higher growth velocity, or improved height-for-age z-scores. Experimental studies showed significant increases in linear growth among children who received milk regularly, whereas some observational studies reported non-significant associations or results dependent on statistical adjustment. One study assessing complete cow’s milk exclusion observed deceleration in linear growth. Overall, the risk of bias was predominantly moderate. Conclusions: Habitual consumption of liquid cow’s milk during childhood appears to be predominantly associated with favorable linear growth outcomes, although variability exists according to study design, age at exposure, milk type, and exposure assessment. Further research using more robust designs is warranted to clarify the magnitude of the association, potential mechanisms, and implications for weight-related outcomes. Full article

Background: Non-suicidal self-injury (NSSI) is highly prevalent during adolescence and is associated with a range of emotional, cognitive, and interpersonal vulnerabilities. Although prior research has identified key correlates such as emotion dysregulation, hopelessness, interpersonal distress, and attachment insecurity, these factors have largely been examined in isolation, limiting understanding of how they jointly contribute to NSSI. Methods: The present study examined the network structure of NSSI and associated vulnerability processes in a community sample of 2067 Spanish adolescents (M age = 14.62, SD = 1.80). A regularized partial correlation network (EBICglasso) was estimated, including NSSI frequency and functions, emotion dysregulation, hopelessness, perceived burdensomeness, thwarted belongingness, and attachment representations. Centrality and network stability were evaluated using standard indices and bootstrapping procedures. Results: The network revealed a differentiated structure of associations. Perceived burdensomeness and intrapersonal NSSI functions emerged as the most influential nodes, whereas emotion dysregulation occupied a key bridging position connecting attachment-related experiences, interpersonal vulnerability, and NSSI processes. In contrast, NSSI frequency and interpersonal functions showed a more peripheral role. Attachment security was negatively associated with core risk variables, consistent with a protective role within the network. Conclusions: Findings suggest that NSSI in adolescence is embedded within a system of interacting emotional and interpersonal processes, structured around the functional meaning of the behavior and key interpersonal appraisals. Emotion dysregulation emerged as a highly connected node linking multiple domains, while attachment was associated with several key variables within the network. These findings suggest potential targets for early identification and intervention, particularly focusing on emotion regulation, perceived burdensomeness, and intrapersonal functions of NSSI. Full article

Background: Antimicrobial resistance (AMR) is widely considered to be driven by antimicrobial consumption through within-host selection. However, whether this mechanism adequately explains population-level patterns of resistance in invasive infections remains uncertain. If antimicrobial use is the dominant determinant, resistance should be highest in demographic groups with the greatest exposure. Methods: We conducted a retrospective analysis of 44,792 community-onset Escherichia coli bloodstream infection episodes identified through national Australian surveillance data (2013–2024). Resistance prevalence across individual antimicrobials and composite multidrug resistance panels was analysed by age and sex. These data were compared with community antimicrobial dispensing derived from the Pharmaceutical Benefits Scheme. Mean resistance was modelled as a function of age and sex. Results: Antimicrobial use was substantially higher in females than males (~23% overall) and increased markedly with age, with individuals aged ≥80 years receiving approximately three times more antimicrobials than those aged 25–30 years. In contrast, resistance was consistently lower in females across most antimicrobials and composite measures. Resistance demonstrated an inverted U-shaped age distribution, peaking at 30–40 years before declining in older age groups. From early adulthood to older age, antimicrobial dispensing increased threefold, whereas mean resistance declined by approximately 20%. These patterns were consistent across antimicrobial classes, years, and jurisdictions. Conclusions: These findings show that demographic patterns of antimicrobial resistance in community-onset E. coli bloodstream infections are not well explained by a simple population-level consumption model. These findings should be interpreted as important hypothesis-generating insights. Although antimicrobial exposure remains important for individual-level selection, the observed discordance between prescribing and resistance suggests that other factors, including differences in transmission pathways, healthcare contact, disease prevalence, community sanitation and socioeconomic circumstances may also significantly shape resistance patterns. Full article