Search Results (4,611)

B-cell lymphomas, including Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL), evade CD4+ T-cell immunity through novel HLA class II-associated immunosuppressive mechanisms. Despite expressing surface HLA-DR, these tumors fail to activate antigen-specific CD4+ T cells, independent of co-stimulation or PD-L1 checkpoint inhibition. We identified lymphoma-secreted factors that broadly disrupt HLA class II-mediated antigen presentation in both malignant B cells and dendritic cells (DCs), silencing T-cell responses. This inhibition is allele-independent (affecting DR1, DR4, DR7) but spares HLA class I-mediated CD8+ T-cell recognition, indicating a targeted immune evasion strategy. Biochemical and mass spectrometry (MALDI-MS) analyses revealed unique low-molecular-weight peptides (693–790 Da) in BL cells, absent in normal B cells, which may mediate this suppression. Functional fractionation confirmed bioactive inhibitory fractions in lymphoma lysates, further implicating tumor-intrinsic molecules in immune escape. These findings highlight a previously unrecognized axis of B-cell lymphoma immune evasion, where secreted factors disable HLA class II function across antigen-presenting cells. Therapeutically, neutralizing these immunosuppressive molecules could restore CD4+ T-cell surveillance and enhance immunotherapies in B-cell malignancies. This work underscores the importance of HLA class II dysfunction in lymphoma progression and identifies candidate targets for reversing immune suppression. Full article

Introduction: Here we consider the collision of a genetic factor and an essential instigator in Alzheimer’s neuropathogenesis: (i) the Alzheimer’s gene (APOEε4), which downregulates lysosomal autophagy and induces synthesis of (ii) the instigator, interleukin-1β (IL-1β), which drives synthesis of βAPP for Aβ plaques and of MAPKp38 for phosphorylation of tau for formation of neurofibrillary tangles (NFTs), the two cardinal features of AD. Methods: RT-PCR, immunoblotting and immunohistochemistry techniques were used to assess the levels of IL-1β and its signaling cascade in ADε4,4, ε3,3, and age-matched controls (AMC3,3) in hippocampal regions of the brain. Results: IL-1β and its downstream signaling proteins TLR-2, MyD88, NFκB, COX-1, and COX-2 were greater in tissues from ADε4,4 than ADε3,3 or AMC3,3. Cathepsin B, D, and L levels, which play a pivotal role and are necessary for lysosomal autophagy, were lower in ADε4,4 than in ADε3,3 or AMC ε3,3. IL-1β and its downstream signaling cascade TLR-2, MyD88, NFκB, COX-1, and COX-2 expression levels were high in SH-SY5Y and T98G cells transfected with APOεE4. Conclusions: APOEε4 causes Alzheimer’s by downregulating autophagy, thus inducing IL-1β for Aβ plaque and neurofibrillary tangle formation. Full article

Background: Dietary advice for Paralympic athletes (PAs) with a spinal cord injury (PAs-SCI) requires particular attention and has been widely studied. However, currently, no particular attention has been addressed to nutritional guidelines for athletes with an amputation (PAs-AMP). This study aimed at filling up this gap, at least partially, and compared veteran PAs-SCI with PAs-AMP. Methods: A sample of 25 male PAs (12 with SCI and 13 with AMP), recruited during two training camps, was submitted to the following questionnaires: allergy questionnaire for athletes (AQUA), Nordic Musculoskeletal Questionnaire (NMQ), Starvation Symptom Inventory (SSI), neurogenic bowel dysfunction (NBD), orthorexia (ORTO-15/ORTO-7), alcohol use disorders identification test (AUDIT), and Mediterranean diet adherence (MDS). The PAs were also submitted to the following measurements: dietary Oxygen Radical Absorbance Capacity (ORAC) and intakes, body composition, handgrip strength (HGS), basal energy expenditure (BEE), peak oxygen uptake (VO_2peak), peak power, peak heart rate (HR), post-exercise ketosis, and antioxidant response after a cardiopulmonary exercise test (CPET) to voluntary fatigue. Results: Compared to PAs-AMP, PAs-SCI had higher NBD and lower VO_2peak (p < 0.05), peak power, peak HR, peak lactate, phase angle (PhA) of the dominant leg (p < 0.05), and ORTO15 (p < 0.05). The latter was related to NBD (r = −0.453), MDS (r = −0.638), and ORAC (r = −0.529), whereas ORTO7 correlated with PhA of the dominant leg (r = 0.485). Significant differences between PAs-AMP and PAs-SCI were not found in the antioxidant response, glucose, and ketone levels after CPET, nor in dietary intake, AUDIT, AQUA, NMQ, SSI, BEE, HGS, and FM%. Conclusions: The present study showed that PAs-SCI and PAs-AMP display similar characteristics in relation to lifestyle, energy intake, basal energy expenditure, and metabolic response to CPET. Based on both the similarities with PAs-SCI and the consequences of the limb deficiency impairment, PAs-AMP and PAs-SCI require personalized nutritional advice. Full article

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Background: Meniere’s disease is characterized by a triad of vertigo episodes, fluctuating hearing loss, and tinnitus. The disease is followed by a loss of quality of life in patients, with the severity depending on the individual and the stage of the disease. Since there are no quantitatively validated tests that connect all elements of the disease, the only source of subjective data that can be analyzed is the disease diary and questionnaires, among which the MDPOSI (Meniere’s Disease Patient-Oriented Symptom-Severity Index) stands out as a designated quality-of-life assessment tool. This study aims to evaluate the differences in the questionnaire depending on the clinical characteristics of the disease. Methods: The study recruited 60 patients, with clinical variables including age, gender, disease laterality, caloric testing results, and PTA results, the presence of spontaneous nystagmus, pathological values of calorimetric testing, or rotatory chair testing abnormalities. Results: The appearance of spontaneous nystagmus showed a significant association with worse hearing threshold values at 500 Hz (p = 0.036, OR 4.416) and higher. Worse SRT scores correlated with Q1 (p = 0.011), Q2 (p = 0.028), Q4 (p = 0.045), Q5 (p = 0.013), and the total MDPOSI score (p = 0.008, 0.339). Multivariate analysis showed that a higher total value of the MDPOSI questionnaire was statistically significantly associated with older age (p = 0.042) and spontaneous nystagmus (p = 0.037). Conclusions: There is a correlation between the clinical characteristics of Meniere’s disease and the MDPOSI questionnaire, making it useful for assessing quality of life and disease progression. Full article

Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right heart that has fewer assumptions, resulting in increased accuracy and precision. Echocardiography continues to be the first-line imaging modality for diagnostic analysis and the management of acute and chronic right heart failure because of its portability, versatility, and affordability compared to cardiac computed tomography, magnetic resonance imaging, nuclear scintigraphy, and positron emission tomography. Virtually all echocardiographic parameters have been well-validated and have demonstrated prognostic significance. The goal of this narrative review of the echocardiographic parameters of the right heart chambers and hemodynamic alterations associated with right ventricular dysfunction is to present information that must be acquired during each examination to deliver a comprehensive assessment of the right heart and to discuss their clinical significance in right heart failure. Methods: Using a literature search in the PubMed database from 1985 to 2025 and the Cochrane database, which included but was not limited to terminology that are descriptive of right heart anatomy and function, disease states involving acute and chronic right heart failure and pulmonary hypertension, and the application of conventional and advanced echocardiographic modalities that strive to elucidate the pathophysiology of right heart failure, we reviewed randomized control trials, observational retrospective and prospective cohort studies, societal guidelines, and systematic review articles. Conclusions: In addition to the conventional 2-dimensional echocardiography and color, spectral, and tissue Doppler measurements, a contemporary echocardiographic assessment of a patient with suspected or proven right heart failure must include 3-dimensional echocardiographic-derived measurements, speckle-tracking echocardiography strain analysis, and hemodynamics parameters to not only characterize the right heart anatomy but to also determine the underlying pathophysiology of right heart failure. Complete and point-of-care echocardiography is available in virtually all clinical settings for routine care, but this imaging tool is particularly indispensable in the emergency department, intensive care units, and operating room, where it can provide an immediate assessment of right ventricular function and associated hemodynamic changes to assist with real-time management decisions. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequencing on skeletal muscle samples from 19 human patients with ER history, collected at a minimum of six months after the most recent ER event, and eight healthy controls to investigate the transcriptomic landscape of ER. To identify any alterations in biological processes between the case and control groups, functional pathway analyses were conducted. Results: Functional pathway enrichment analyses of differentially expressed genes revealed strong suppression of mitochondrial function. This suppression included the “aerobic electron transport chain” and “oxidative phosphorylation” pathways, indicating impaired energy production. Conversely, there was an upregulation of genes associated with adhesion and extracellular matrix-related pathways, indicating active restoration of muscle function in ER cases. Conclusions: The study demonstrated that muscle tissue exhibited signs of suppressed mitochondrial function and increased extracellular matrix development. Both of these facilitate muscle recovery within several months after an ER episode. Full article

This pilot, randomized, double-blind, placebo-controlled trial investigated the effects of branched-chain amino acids (BCAAs)—provided in a 2:1:1 ratio of leucine:isoleucine:valine—combined with exercise on fatigue, physical performance, and quality of life in older adults. Twenty participants (63% female; BMI: 35 ± 2 kg/m²; age: 70.5 ± 1.2 years) were randomized to 8 weeks of either exercise + BCAAs (100 mg/kg body weight/d) or exercise + placebo. The program included moderate aerobic and resistance training three times weekly. Physical function was assessed using handgrip strength, chair stands, gait speed, VO₂ max, and a 400 m walk. Psychological health was evaluated using the CES-D, Fatigue Assessment Scale (FAS), Insomnia Severity Index (ISI), and global pain, fatigue, and quality of life using a visual analog scale (VAS). Significant group x time interactions were found for handgrip strength (p = 0.03), chair stands (p < 0.01), and 400 m walk time (p < 0.01). Compared to exercise + placebo, exercise + BCAAs showed greater improvements in strength, mobility, and endurance, along with reductions in fatigue (−45% vs. +92%) and depressive symptoms (−29% vs. +5%). Time effects were also observed for ISI (−30%), FAS (−21%), and VAS quality of life (16%) following exercise + BCAA supplementation. These preliminary results suggest that BCAAs combined with exercise may be an effective way to improve physical performance and reduce fatigue and depressive symptoms in older adults. Full article

Transportation is often cited as a significant barrier to healthcare access by Veterans, particularly those from minority groups, who have disabilities, or live in rural areas. Autonomous shuttles (AS) offer a potential solution, yet limited research has explored Veterans’ experiences with this technology. This study qualitatively investigated Veterans’ lived experiences with AS through focus groups, enrolling participants aged 18+ from Gainesville, The Villages, and Lake Nona, Florida. Via a directed content analysis, six key themes were identified: Perceived Benefits, Safety, Experience with Autonomous Vehicles (AV), AS Experience, AV Adoption, and Perception Change. Among 26 participants (aged 30–85; 77% men; 88% urban residents), prominent themes included Safety (n = 161), Perceived Benefits (n = 153), and AS Experience (n = 118), with predominantly positive counts in all themes except AS Experience. Participants acknowledged safety advantages and multitasking potential of AS over human-operated vehicles while recommending improvements to the shuttle’s slow speed, availability and convenience. While the AS ride was positively received overall, some participants noted issues with comfort and braking, emphasizing the need for further technological enhancements. Real-world exposure to AS appeared to influence acceptance positively, offering insights for policymakers and industry stakeholders aiming to optimize AS deployment for mobility-vulnerable Veterans. Full article

Background/Objectives: This study aimed to identify the risk factors for respiratory failure in patients with intracerebral hemorrhage (ICH) accompanied by intraventricular hemorrhage (IVH) extension. Methods: We retrospectively included 208 patients with ICH accompanied by IVH extension. Respiratory failure was defined as carbon dioxide levels > 45 mmHg with a pH < 7.35 in arterial blood gas analysis (ABGA) or the application of a ventilator due to respiratory dysfunction. We measured the severity of IVH extension using the Graeb scale, and ICH volume was assessed for each patient. Results: Of the 208 included patients, 83 had respiratory failure. There were no significant differences in age, sex ratio, or Graeb scale score between patients with and without respiratory failure (p > 0.05). However, ICH volume was significantly larger in patients with respiratory failure (42.0 ± 42.5 mL) than in those without (26.4 ± 25.7 mL) (p = 0.003). In the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve for ICH volume predicting respiratory failure was 0.612. The optimal threshold for detecting respiration failure in patients with ICH and IVH dilatation, based on the Youden index, was >63.2 mL, with a sensitivity of 30.12% and a specificity of 89.60%. Approximately 40% of patients experienced respiratory failure following ICH accompanied by IVH extension. Conclusions: A large ICH volume was associated with the occurrence of respiratory failure. Therefore, caution is required in patients with an ICH volume > 63.2 mL. Full article

Background: Congenital anosmia (CA) is a rare condition characterized by a lifelong inability to perceive odors, which significantly affects daily life and may be linked to broader neurodevelopmental alterations. This study aimed to investigate structural brain differences in patients with CA using MRI, focusing on gray matter (GM) and white matter (WM) changes and their implications for neurodevelopment. Methods: This retrospective study included 28 patients with CA and 28 age- and gender-matched healthy controls. Patients with CA were diagnosed at a single medical center between 1 January 2001 and 30 August 2024. Controls were randomly selected from an imaging database and had no history of olfactory dysfunction. Brain Magnetic Resonance Imaging (MRI)was analyzed using volumetric analysis in SPM12.GM and WM volumes were quantified across 11 anatomical brain regions based on theWFU_PickAtlas toolbox, including frontal, temporal, parietal, occipital, limbic, sub-lobar, cerebellum (anterior/posterior), midbrain, the pons, and the frontal–temporal junction. Left–right hemispheric comparisons were also conducted. Results: Patients with CA exhibited significantly smaller GM volumes compared to healthy controls (560.6 ± 114.7 cc vs. 693.7 ± 96.3 cc, p < 0.001) but larger WM volumes (554.2 ± 75.4 cc vs. 491.1 ± 79.7 cc, p = 0.015). Regionally, GM reductions were observed in the frontal (131.9 ± 33.7 cc vs. 173.7 ± 27.0 cc, p < 0.001), temporal (81.1 ± 18.4 cc vs. 96.5 ± 14.1 cc, p = 0.001), parietal (52.4 ± 15.2 cc vs. 77.2 ± 12.4 cc, p < 0.001), sub-lobar (57.8 ± 9.7 cc vs. 68.2 ± 10.2 cc, p = 0.001), occipital (39.1 ± 13.0 cc vs. 57.8 ± 8.9 cc, p < 0.001), and midbrain (2.0 ± 0.5 cc vs. 2.3 ± 0.4 cc, p = 0.006) regions. Meanwhile, WM increases were notable in the frontal(152.0 ± 19.9 cc vs. 139.2 ± 24.0 cc, p = 0.027), temporal (71.5 ± 11.5 cc vs. 60.8 ± 9.5 cc, p = 0.001), parietal (75.8 ± 12.4 cc vs. 61.9 ± 11.5 cc, p < 0.001), and occipital (58.7 ± 10.3 cc vs. 41.9 ± 7.9 cc, p < 0.001) lobes. A separate analysis of the left and right hemispheres revealed similar patterns of reduced GM and increased WM volumes in patients with CA across both sides. An exception was noted in the right cerebellum-posterior, where patients with CA showed significantly greater WM volume (5.625 ± 1.667 cc vs. 4.666 ± 1.583 cc, p = 0.026). Conclusions: This study demonstrates widespread structural brain differences in individuals with CA, including reduced GM and increased WM volumes across multiple cortical and sub-lobar regions. These findings suggest that congenital olfactory deprivation may impact brain maturation beyond primary olfactory pathways, potentially reflecting altered synaptic pruning and increased myelination during early neurodevelopment. The involvement of the cerebellum further implies potential adaptations beyond motor functions. These structural differences may serve as potential neuroimaging markers for monitoring CA-associated cognitive or emotional comorbidities. Full article

Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs. partial thymectomy for early-stage thymoma. Methods: We identified patients diagnosed with WHO types A–B3 thymoma between 2010–2021 from a national hospital-based dataset. We excluded patients with stage II or higher disease, open resections and perioperative chemo-/radiation therapy. We stratified patients into total and partial thymectomy cohorts. We used propensity score matching to minimize confounding, Kaplan–Meier analysis to estimate survival, and Cox proportional hazards to identify associations. Results: Of 1598 patients with early-stage thymoma, 495 (31.0%) underwent partial and 1103 (69.0%) total thymectomy. Patients undergoing partial thymectomy were similar in sex (female 53.7% vs. 53.4%; p = 0.914), race (white 74.5% vs. 74.0%; p = 0.921), comorbidities (0 in 77.0% vs. 75.5%; p = 0.742), and tumor size (48.7 mm vs. 50.4 mm; p = 0.455) compared to total thymectomy. There were no differences in 30-day (0.8% vs. 0.6%, p = 0.747) or 90-day mortality (0.8% vs. 0.8%, p > 0.999), which persisted after matching. Moreover, 10-year survival was similar in both unmatched (p = 0.471) and matched cohorts (p = 0.828). Partial thymectomy was not independently associated with survival (aHR = 1.00, p = 0.976). Conclusions: In patients with early-stage thymoma, partial and total thymectomy were associated with similar short- and long-term outcomes. In light of recent attention to the role of the thymus gland, the results add important insights to shared decision-making discussions. Full article

Myocardial infarction (MI) remains one of the most common cardiovascular diseases and a leading cause of morbidity and mortality worldwide. In recent years, natural polymeric patches have attracted increasing attention as a promising therapeutic platform for myocardial tissue repair. This study explored the fabrication and evaluation of screen-printed electrodes (SPEs) on chitosan film as a novel platform for cardiac patch applications. Chitosan is a biodegradable and biocompatible natural polymer that provides an ideal substrate for SPEs, providing mechanical stability and promoting cell adhesion. Silver ink was employed to enhance electrochemical performance, and the electrodes exhibited strong adhesion and structural integrity under wet conditions. Mechanical testing and swelling ratio analysis were conducted to assess the patch’s physical robustness and aqueous stability. Silver ink was employed to enhance electrochemical performance, which was evaluated using cyclic voltammetry. In vitro, electrical stimulation through the chitosan–SPE patch significantly increased the expression of cardiac-specific genes (GATA-4, β-MHC, troponin I) in bone marrow mesenchymal stem cells (BMSCs), indicating early cardiogenic differentiation potential. In vivo, the implantation of the chitosan–SPE patch in a rat MI model demonstrated good tissue integration, preserved myocardial structure, and enhanced ventricular wall thickness, indicating that the patch has the potential to serve as a functional cardiac scaffold. These findings support the feasibility of screen-printed electrodes fabricated on chitosan film substrates as a cost-effective and scalable platform for cardiac repair, offering a foundation for future applications in cardiac tissue engineering. Full article

Background: As COVID-19 transitions to an endemic phase, long COVID symptoms remain a significant public health issue affecting both physical and mental health. A notable proportion of college students report symptoms such as fatigue, cough, and brain fog persisting for weeks or months post-infection. Objectives: This study explored the prevalence and contributing factors of long COVID symptoms among both infected and uninfected students in medicine-related departments. Methods: A cross-sectional study was conducted using online self-reported questionnaires completed by 1523 undergraduate and graduate students in medicine-related departments at a medical university. Participants who had tested positive for COVID-19 within the past three months were excluded. The survey assessed long COVID symptoms, with comparisons conducted between infected and uninfected groups. Multivariate logistic regression identified risk factors associated with long COVID symptoms. Results: Of the 1118 participants, 47.5% of those with a prior COVID-19 diagnosis reported long COVID symptoms within the past month. Significant differences between the infected and uninfected groups were observed in physical, cognitive, and psychological health. Logistic regression identified that prior COVID-19 diagnosis had an association with the presence of long COVID symptoms (odds ratio = 1.48, p = 0.024) after adjusted model analysis. Meanwhile, higher anxiety levels (odds ratio = 1.09, p < 0.001) and a BMI ≥ 24 (odds ratio = 4.50, p < 0.01) were identified as significant risk factors for post-infection syndrome among previously infected students. Sex and exercise habits also influenced symptom prevalence. Conclusions: Since late 2023, with those experiencing cumulative infections surpassing half of Taiwan’s population, long COVID symptoms have persisted as a widespread concern affecting both physical and mental health, continuing into 2025. This study underscores critical risk factors and symptom patterns among students in medicine-related departments, reinforcing the urgency of sustained surveillance and targeted interventions to facilitate comprehensive recovery. Full article