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Lecanemab is a monoclonal antibody targeting amyloid-beta protofibrils, indicated for patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease. This study reports interim findings of an ongoing, multicenter, prospective, observational post-marketing study for all patients treated with lecanemab in routine clinical practice in Japan, focusing on amyloid-related imaging abnormalities (ARIAs) and infusion-related reactions primarily observed during up to 28 weeks after treatment initiation. Patients treated with lecanemab at any medical institutions across Japan are included in the study. Data are collected using an electronic data capture system via standardized case report forms (CRFs). Study items included the incidence of ARIA, ARIA-edema or effusion (-E), ARIA-hemorrhage (-H: cerebral microhemorrhages, superficial siderosis, and macrohemorrhage), and infusion-related reactions, reported as adverse drug reactions. As of July 5, 2025, CRFs from 2675 patients were collected, of whom 2672 had data available for the interim analysis. The median age was 76.0 years, and 62.6 % (1672/2672) of patients were diagnosed with MCI. At Week 28, 7.3 % (195/2672) of patients discontinued treatment, with a mean treatment duration of 189.6 ± 34.4 days. Among 2634 patients confirmed to have undergone MRI scans after treatment initiation, ARIA was observed in 7.1 % (188/2634) of patients, ARIA-E in 3.0 % (78/2634), and ARIA-H in 5.2 % (137/2634). Serious ARIA-H (macrohemorrhage) occurred in two patients (0.1 %). Infusion-related reactions were observed in 17.0 % (455/2672), including 0.7 % (18/2672) serious cases. The proportion of patients who experienced ARIA was highest in patients with apolipoprotein E (APOE) ε4 homozygotes. This interim analysis represents one of the largest real-world lecanemab cohorts reported globally to date. Although absolute rates are not directly comparable with those from clinical trials, the trends in ARIA distributions across APOE genotypes and infusion-related reactions were comparable to those observed in clinical trials. Show less

Diabetic peripheral neuropathy (DPN), a severe complication of diabetes, is a key risk factor for diabetic foot (DF) that contributes highly to amputation and mortality. The pathogenesis of DPN remains unclear and complex, with no effective treatments currently available. Monoamine oxidase (MAO), a flavin adenine dinucleotide (FAD)-dependent enzyme, catalyzes the oxidative deamination of critical biogenic amines. The MAO family comprises two subtypes, MAOA and MAOB, which play distinct roles in pathophysiology. In this study, we identified that MAOB but not MAOA is pathologically upregulated in the sciatic nerve (SN) tissues of DPN patients and in the SN/dorsal root ganglion (DRG) tissues of DPN model mice. Notably, the selective MAOB inhibitor Khellin (Khe) effectively alleviated DPN-like pathology in mice. To explore the mechanistic role of MAOB in DPN, we performed proteomic profiling of DRG tissues from DPN mice and validated the findings using a MAOB-specific knockdown DPN mice model treated with adeno-associated virus (AAV) 8-MAOB-RNAi. Our results demonstrate that Khe targets MAOB to mitigate DPN pathology through HIF-1α/BACE1/Aβ/NLRP3/tau pathway, mediated by Schwann cell/DRG neuron crosstalk. All findings suggest that selective MAOB inhibition represents a promising therapeutic strategy for DPN, with Khe as a potential candidate for clinical translation against this disease. Show less

While family resilience is a recognized determinant of adaptation following stroke, the distinct, empirically derived profiles of family resilience among Chinese stroke survivor-caregiver dyads have not been clearly delineated. Identifying these profiles and their determinants is crucial for developing targeted interventions. To identify latent profiles of family resilience and examine the socio-demographic and clinical factors associated with profile membership among stroke patient-caregiver dyads in China. In this cross-sectional study, a convenience sample of 773 stroke survivor-caregiver dyads was recruited from three hospitals in Zhejiang Province, China. Latent profile analysis (LPA) was conducted on the 20-item Family Resilience Questionnaire (FRQ). Multinomial logistic regression was used to determine factors associated with profile membership. LPA supported a four-profile solution: Profile 1 "Low-Functioning Families" (22%), Profile 2 "Moderately Resilient - Low Cohesive Families" (24%), Profile 3 "Highly Resilient - Well-Functioning Families" (31%), and Profile 4 "High-Functioning - Optimistically Resilient Families" (24%). Multinomial logistic regression revealed that lower caregiver competence (higher FCTI scores) was strongly associated with profile membership (standardized aORs ranged from 2.58 to 43.19), whereas higher perceived social support (PSSS) was a significant protective factor (standardized aORs ranged from 0.03 to 0.19). Caregiver relationship and payment source were also significantly associated with profile membership. Family resilience among Chinese stroke families manifests in four distinct profiles, which are differentiated predominantly by caregiver competence and perceived social support. Our findings advocate for a precision family support paradigm, shifting from one-size-fits-all approaches to interventions tailored to distinct resilience profiles. Given the strong association, intervention programs should prioritize enhancing core caregiver competencies as a primary leverage point for building family resilience. Show less

Current treatments for idiopathic pulmonary fibrosis (IPF) slow but do not stop/reverse disease progression. The lysophosphatidic acid (LPA) axis is identified as a therapeutic target for IPF. This study aims to assess BI 1819479, an LPA pathway inhibitor, in patients with IPF (ClinicalTrials.gov Identifier: NCT06335303). In this placebo-controlled, phase II trial, patients will be randomised (2:1:1:1) to receive one of three oral doses of BI 1819479 or placebo, stratified by nintedanib/pirfenidone use. Patients aged ≥40 years with IPF, forced vital capacity (FVC) ≥45% of predicted normal and haemoglobin-corrected diffusing capacity for carbon monoxide ≥25% of predicted normal at screening will be included. Patients with relevant airway obstruction (pre-bronchodilator forced expiratory volume in 1 s/FVC <0.7), acute IPF exacerbation ≤12 weeks prior to screening, treatment with immunosuppressive medications (other than oral corticosteroids) or prednisone >15 mg·day This trial evaluates the efficacy, safety and dose range of BI 1819479 in patients with IPF, offering a potential additional treatment option, and will establish appropriate dosing for phase III trials. Show less

Sevoflurane, a widely used volatile anesthetic, has raised concerns regarding its potential developmental toxicity, particularly due to its extensive application in non-obstetric surgeries and fetal intervention procedures during pregnancy. However, its effects on heart development and function remain unclear. Using zebrafish larvae as a model, we investigated the effects of prolonged sevoflurane exposure (0.04-0.08%) from 10 to 72 h post-fertilization (hpf). Under these conditions, treated larvae exhibited dose-dependent developmental abnormalities, including reduced body length, pericardial edema, and impaired heart tube looping. Cardiac function analysis revealed significant decreases in ejection fraction, stroke volume, heart rate, and cardiac output, indicating impaired cardiac contractility and pumping efficiency. These functional impairments were accompanied by structural changes including ventricular wall thinning and chamber dilation, along with upregulation of cardiac stress markers (nppa, nppb) - characteristic features of dilated cardiomyopathy (DCM). Molecular analysis demonstrated downregulation of sarcomeric (tnnt2a, mybpc3) and calcium-handling (atp2a2a, slc8a1a) genes, suggesting disruption of sarcomere integrity and calcium homeostasis. Additionally, sevoflurane exposure elevated inflammatory cytokines (il-6, tnf-α, il-1β) and promoted leukocyte infiltration into cardiac tissue. RNA sequencing analysis implicated dysregulation of Apelin signaling pathway, with reduced prkaa2 (AMPKα2) expression and phosphorylation observed in both zebrafish and H9C2 cardiomyocytes. Critically, pharmacological activation of AMPK using A-769662 effectively mitigated sevoflurane-induced cardiotoxicity, identifying AMPKα2 as a potential therapeutic target. Collectively, these findings delineate the molecular mechanisms underlying sevoflurane-induced developmental cardiotoxicity following prolonged exposure in zebrafish and suggest that targeting AMPKα2 signaling merits investigation as a potential strategy to mitigate anesthetic-related cardiac developmental risks. Show less

Rosette-forming glioneuronal tumors (RGNTs) are rare, World Health Organization grade 1 tumors that typically arise around the fourth ventricle. However, cerebral hemisphere RGNTs have recently been reported, with some exhibiting clinical features resembling low-grade epilepsy-associated tumor (LEAT). We report a case of multifocal RGNT in a patient with drug-refractory epilepsy. A 14-year-old woman was incidentally found to have multifocal brain tumor involving the left temporal lobe and bilateral thalamus, she developed drug-resistant epilepsy ten years later and underwent surgery. Partial tumor resection and anterior temporal lobectomy were performed. Histopathology revealed a glioneuronal tumor with oligodendroglia-like cells, neurocytic rosette, and perivascular pseudorosette, exhibiting an infiltrative growth pattern extending into the white matter. Genetic analysis revealed Fibroblast Growth Factor Receptor 1 mutation. The methylation profile analysis matched the low-grade glioneuronal tumor class but did not yield to any subclass category. Finally, the tumor was diagnosed as RGNT-like low-grade glioneuronal tumor with dysembryoplastic neuroepithelial tumor (DNT) features. Cases presenting with a LEAT-like clinical course and exhibiting histopathological features of RGNT are often difficult to definitively distinguish from DNT based on histological and genetic findings. Epilepsy-associated RGNT may harbor genetic profiles distinct from those of prototypical RGNTs, highlighting the need for further investigation. Show less

To examine associations between the 24-h composition of movement behaviors (sedentary behavior [SB], light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], and sleep) and physical and mental health in older adults using compositional data analysis. Data came from 4,150 adults aged ≥ 60 in the 2015 China Health and Nutrition Survey. Multiple‑balance isometric log‑ratio regression and compositional isotemporal substitution models were used to assess relative associations and the effect of time reallocation. The 24‑hour geometric mean composition was 43.1% sleep, 30.6% SB, 21.8% LPA, and 4.5% MVPA. LPA was positively associated with physical (β = 0.062, Replacing sedentary time or sleep with LPA, even in small amounts, is associated with better physical and mental health in older adults, supporting integrated 24‑hour activity guidelines that emphasize light‑intensity movement. Show less

High-grade serous ovarian cancer (HGSC) is the most aggressive subtype of ovarian epithelial cancer (OEC), with characters of late-stage diagnosis, high recurrence rate, and poor survival outcomes. Fucosyltransferase 8 (FUT8) is responsible for α1,6-core fucosylation biosynthesis, and aberrant FUT8/α1,6-core fucosylation level is involved in tumor progression. However, the roles and mechanisms of protein FUT8 and α1,6-core fucosylation in HGSC tumorigenesis and progression remain elusive. Here, our study confirms that elevated levels of FUT8/α1,6-core fucose in the tissues and serum of HGSC patients, and the elevation is associated with poor patient prognosis. By applying glycoproteomic assay, we globally screen and identify NCEH1 as the specific scaffold protein of α1,6-core fucosylation. Alpha 1,6-core fucose modification stabilizes NCEH1 by preventing its degradation through proteasomal pathway. Importantly, combined with non-targeted metabolomics analysis, α1,6-core fucosylated NCEH1 facilitates LPA secretion, driving M2-like polarization of tumor-associated macrophages in the tumor microenvironment, thus leading to oncogenesis and peritoneal metastasis of HGSC in vitro and in vivo. These findings broaden the understanding of FUT8/α1,6-core fucosylation/NCEH1 in HGSC progression and metastasis, and offer glycosylated diagnostic indicators and targets for therapeutic strategies in HGSC. Show less

Probiotics such as The intestinal colonization ability of CIQ249 was assessed using cFDA-SE labeling and flow cytometry. Growth performance and intestinal morphology were evaluated in mice. Antimicrobial activity of CIQ249 cell-free supernatant was tested against various pathogens, and pathogen damage was visualized by scanning electron microscopy. Protective effects against CIQ249 demonstrated strong intestinal colonization and increased villus height and the villus-to-crypt ratio, contributing to improved growth performance. Its cell-free supernatant selectively inhibited enteropathogens and induced structural damage in CIQ249 enhances mucosal defense against enteropathogenic bacteria through a dual mechanism-strengthening the epithelial barrier and activating a coordinated DC-Tfh-IgA immune axis. These findings provide a multi-level mechanistic basis for its application as a microecological agent against intestinal infections. Show less

High-grade astrocytoma with piloid features (HGAP) has recently emerged as an aggressive glioma entity with distinct molecular alterations, yet its clinicogenomic distinction from pilocytic astrocytoma (PA) remains to be fully elucidated. This study aims to clarify the clinical, pathological, and genomic differences between pediatric PA, adult PA, and HGAP, and to provide evidence supporting the recognition of HGAP as a new, aggressive entity. We retrospectively analyzed 100 genetically and histopathologically confirmed PA cases (87 pediatric, 13 adult) and 25 HGAP cases (all > 19 years old) diagnosed at Seoul National University Hospital between 2015 and 2024. Next-generation sequencing using a brain tumor-specific gene panel and immunohistochemistry evaluation. Pediatric PAs (median age 7 years) were predominantly cerebellar (61%) and showed classic biphasic histology (72%) with frequent HGAP represents a clinically aggressive and molecularly distinct high-grade glioma, clearly separable from pediatric and adult PA. Its poor prognosis and unique genetic drivers justify its recognition as a new entity. Accurate molecular profiling is essential for diagnosis and management of these tumors, and the poor survival outcomes observed in HGAP highlight the need for further larger cohort studies to identify optimal therapeutic strategies. Show less

Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a temporally controlled hydrogel microneedle system that integrates ginseng-derived exosomes (G-Exos) with biomimetic polydopamine nanoparticles (PDA@PEGs) to concurrently target the pathogenic triad of vitiligo, including oxidative stress, inflammation, and melanocyte deficiency. This system employs methacrylated hyaluronic acid (HAMA) hydrogel microneedles for rapid PDA@PEG release while utilizing glyceryl monostearate micelles to achieve matrix metalloproteinase-9 (MMP-9)-responsive G-Exo release at inflammatory foci, enabling intelligent spatiotemporal control. Functionally, G-Exos help restore redox homeostasis and suppress inflammation through bioactive constituents, thereby protecting melanocytes and enhancing keratinocyte proliferation. Moreover, PDA@PEG promotes repigmentation through the dual mechanisms of exogenous melanin deposition and endogenous melanogenesis stimulation. In murine models, this strategy achieves significant repigmentation within 3 weeks by activating follicular stem cells, upregulating melanogenic markers (Tyr/Mc1r), increasing antioxidant defense (ApoE), and suppressing inflammatory signaling (IL-17). This natural-biomimetic hybrid design leverages biocompatible materials to co-target multiple pathological axes, offering a novel self-adaptive approach for microenvironmental rehabilitation in vitiligo. Show less

Head and neck cancer (HNC) is a biologically heterogeneous malignancy with limited actionable therapeutic targets. The fibroblast growth factor receptor (FGFR) family comprises receptor tyrosine kinases implicated in tumor progression; however, their specific roles in HNC remain incompletely defined. Genomic alterations, transcriptomic profiles, and clinical relevance of Among FGFR4 functions as an oncogenic driver in HNC, promoting tumor progression through the ERK–RUNX3–MMP2 axis and mediating chemoresistance via FGFR4–ERK signaling. The ERK-dependent induction of FGF19 and FGFR4 establishes a positive feedback circuit that sustains oncogenic activation. Targeting the FGF19/FGFR4 axis, particularly when combined with MEK/ERK inhibitors, represents a promising strategy to overcome resistance in HNC. The online version contains supplementary material available at 10.1186/s12967-026-07999-1. Show less

The long-term effects of SARS-CoV-2 infection are increasingly recognized, with heterogeneous physical and psychological symptoms that may persist for months, significantly affecting Health Related Quality of Life (HRQoL), functional capacity, and psychosocial well-being. This study explores distinct profiles of HRQoL and psychological symptoms in former COVID-19 inpatients and assesses the impact of clinical variables at admission on long-term outcomes. Patients hospitalised for COVID-19 at Molinette Hospital in Turin were contacted several months post-discharge (between June 2022 and June 2023) to complete a questionnaire assessing long-term HRQoL, sleep quality, depression, anxiety, stress, and fatigue. Clinical data at the time of hospitalisation were also available for each participant. A Latent Profile Analysis (LPA) was conducted on these physical and psychological variables, followed by multinomial logistic regression to examine how selected indicators of baseline COVID-19 severity and patient characteristics predicted profile membership. The sample consisted of 601 patients. LPA identified three health-related profiles: This study highlights a wide spectrum of post-COVID-19 conditions, ranging from good to severely compromised physical and mental health. Female gender, presence of comorbidities, and elevated early warning scores at hospital admission are risk factors for worse outcomes, emphasizing the need for comprehensive long-term care. The online version contains supplementary material available at 10.1007/s11136-026-04206-y. Show less

The etiology of Alzheimer's disease (AD) has been extensively studied for a long time, primarily associated with multifaceted mechanisms involving aggregation of amyloid beta, tau hyperphosphorylation, neuroinflammation, and immune regulation. Current therapeutics for AD are significantly targets to attenuate the cognitive decline by modulating neurotransmitters and diminishing aggregation of amyloid beta. However, these therapeutics fail to address the neuroimmune dysregulation that critically facilitates disease progressions. In this study, we have delineated the phytochemical potential to modulate the amyloid beta-triggered immune regulation through in silico approaches. Seventy three phytochemicals were selected from established anti-Alzheimer's plants through literature mining and sequentially administrated to pharmacodynamic and pharmacokinetic investigations. The draggable study has established 14 phytochemicals, and the compounds were further curated based on their molecular interactions with the hub-targets, enriched in the amyloid beta-driven immune regulation. AD-associated proteins were retrieved from different data sets such as GeneCards, DisGeNet, GEO, and Opentargets, and the intersecting targets were curated for downstream analysis. Functional annotation and network pharmacology analysis mapped APOE4, BACE1, TREM2, IL-1β, and TNF-α as key regulatory targets. The molecular interaction analysis revealed that genkwanin and kaempferol exhibited strong binding affinity and stable interactions with the hub-targets as a potent candidates to attenuate the immune regulation in AD. Further molecular mechanics/Poisson-Boltzmannsson-Boltzmann surface area and DFT analysis have revealed their thermodynamic stability and electronic reactivity, highlighting their potential efficacy in mitigating AD progression. Show less

Cancer patients face a markedly elevated risk of thromboembolism (TE), including both venous thromboembolism (VTE) and arterial thromboembolism (ATE), which contribute substantially to morbidity and mortality in this population. This study examined sex disparities in associations between sleep, sedentary behavior (SB), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and TE risk, in cancer patients using data from the UK Biobank. A longitudinal cohort analysis of 6,765 cancer patients (2,774 men and 3,991 women) from the accelerometry subsample was conducted using Cox proportional hazards and isotemporal substitution models stratified by sex. The incidence of VTE was 3.0% in men versus 2.2% in women, while ATE incidence was 5.0% versus 2.2%, respectively. Compared with high LPA, medium and low durations were associated with 2.75- and 2.88-fold higher VTE risk only in men. Reallocating 1 h per day from sleep or SB to LPA reduced VTE risk by 24% and 19% in men. Low MVPA was associated with 3.35- and 1.59-fold higher ATE risk in women and men, respectively. Reallocating 1 h per day from sleep, SB, or LPA to MVPA reduced ATE risk by 71%, 70%, and 66%, respectively, only in women. LPA was associated with a lower risk of VTE only in male cancer patients, whereas MVPA was linked to a lower risk of ATE in female patients, indicating sex-specific associations between movement behaviors and TE risk. Show less

Serum lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease. However, whether hypertension modifies the association between Lp(a) and adverse outcomes in acute decompensated heart failure (ADHF) remains unclear. We investigated how hypertension status influences the relationship between Lp(a) and all-cause mortality in ADHF. We conducted a single-center retrospective observational study including 2610 patients hospitalized with ADHF. We normalized the distribution of Lp(a) by a logarithmic transformation and assessed the risk of all-cause mortality with Lp(a), using Cox regression with adjustment for potential confounders. Among 2610 patients (39.0% women; mean age, 68.8 years), 1606 (61.5%) had hypertension. Over 4.1 years (median), 1287 deaths occurred. In all patients, log-transformed Lp(a) was significantly associated with mortality (adjusted HR 1.21; 95% CI, 1.05-1.39; Increased admission Lp(a) levels were associated with a higher risk of all-cause mortality in ADHF patients with hypertension. Further studies are needed to explore the mechanistic links among Lp(a), hypertension and ADHF. Show less

This study aims to identify the 24-h movement behavior patterns of preschool children using Latent Profile Analysis based on Compositional Data Analysis (CoDA), and to examine their associations with physical fitness. The study employs a cross-sectional design. A total of 329 healthy children aged 4-6 years were selected. Accelerometers (ActiGraph wGT3-BT, Pensacola, FL, USA) were used to measure light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), and sedentary behavior (SB), while sleep was assessed through parent and teacher questionnaires. The assessment of physical fitness was conducted in accordance with the "Chinese National Physical Fitness Test Standards" (Preschooler Section). To address the multicollinearity problems among components of physical activity (PA), CoDA was first applied, subsequently, Latent Profile Analysis was utilized to categorize 24-h movement behavior patterns, while a Generalized Ordered Logit Model (GOLM) was applied to investigate their associations with physical fitness. Three distinct behavioral patterns emerged from the analysis: the "brown bear group" (moderate PA and SB, high SP, N = 176, 53.5%), the "cheetah group" (high PA/MVPA, low SB, moderate SP, N = 102, 31%), and the "koala group" (low PA, high SB, lower SP, N = 51, 15.5%). After adjusting for potential confounding factors, it was found that compared with the "koala group", the "brown bear group" and the "cheetah group" exhibited higher levels of physical fitness, with the probability of improving their physical fitness rating being 3.69 times and 6.36 times that of the "koala group," respectively. This study highlights the significant impact of active and healthy activity patterns on the physical fitness of preschool children, providing a foundation for formulating personalized preventive and interventional approaches in early childhood. Show less

Endothelial lipase (EL) is a key regulator of high-density lipoprotein (HDL) metabolism. Many aspects of EL function remain incompletely understood due to challenges in purifying active EL. This study identifies apolipoprotein J (ApoJ) as a novel chaperone for EL, crucial for its solubility and activity. Using an optimized purification protocol that yields active EL, we discovered that ApoJ consistently co-purifies with EL, maintaining its activity. We further show that knocking down ApoJ decreases the activity of EL. We demonstrate that ApoJ interacts with EL via its hydrophobic lid and tryptophan loop regions, and that mutating these regions abolishes the effect of ApoJ on the solubility and activity of EL. We show that ApoJ, EL, and ApoA1 (the defining lipoprotein of HDL particles) colocalize in HDL particles in mouse plasma. However, we find that ApoJ is not a direct carrier for EL to HDL particles. Instead, our data suggest that ApoJ primarily serves to enhance EL activity through its role as a chaperone, even when incorporated into lipid substrates. Our findings suggest a model in which ApoJ protects EL in plasma and enhances its hydrolysis of lipoprotein substrates. We propose that ApoJ is an accessory protein for EL, analogous to GPIHBP1 for LPL and co-lipase for PL. Further study of the interaction between EL and ApoJ will promote a better understanding of HDL metabolism. Show less

Assessment of muscle coordination during cycling can provide insight into motor control strategies and movement efficiency. This study evaluated muscle synergy patterns as indicators of neuromuscular coordination in the lower limbs across three power levels of cycling (LPL = Lowest Power Level, MPL = Middle Power Level, HPL = Highest Power Level). Twenty recreational cyclists performed a graded cycling test on a stationary bicycle ergometer. Electromyography (EMG) was recorded bilaterally from seven lower-limb muscles and muscle synergies were extracted using non-negative matrix factorization. The Synergy Index (SI) and Synergy Coordination Index (SCI) were calculated to assess muscle coordination patterns. Four muscle synergies were identified consistently across power levels, with changes in synergy composition and activation timing correlated with increasing muscular demands. At the dominant hip, SI remained consistent across power levels (0.50 ± 0.11 at LPL, 0.56 ± 0.15 at MPL, 0.54 ± 0.15 at HPL). At the dominant knee, SI decreased with increasing power (0.47 ± 0.07 at LPL to 0.34 ± 0.05 at HPL; p < 0.01, η These findings provide insight into how the central nervous system modulates its response to increasing mechanical demands. Combining synergy indices offers a promising approach to assess motor control, inform rehabilitation, and optimize performance in cycling tasks. Show less

Lipoprotein(a) [Lp(a)] is a well-established independent risk factor for cardiovascular disease. However, the long-term effects of Lp(a) on coronary plaque phenotype remain unclear. To explore the potential association between Lp(a) levels and coronary plaque volume, composition, and progression using coronary computed tomography angiography (CCTA). Patients with available data for Lp(a) and underwent baseline CCTA examinations between January 2009 to December 2015 and subsequently underwent a follow-up coronary CTA were retrospectively enrolled. Quantitative CCTA analyses measured plaque length, total plaque volume and composition volume. Patients were categorized into an elevated Lp(a) group (≥30 mg/dL) and a normal Lp(a) group (<30 mg/dL). The association between Lp(a) and baseline plaque characteristic and progression were investigated in linear mixed-effects models adjusted for clinical factors. Subgroup analyses were also conducted. Among 453 patients (mean age 64.7 years, 77.7% male) with a median follow-up of 6.15 years. elevated Lp(a) was linked to higher baseline plaque burden (all Elevated Lp (a) level was associated with high coronary artery plaque burden at baseline and rapid progression of LAP at follow-up. Lp(a) may serve as a significant residual risk factor in seemingly "low-risk" populations. Show less

Healthcare professionals are expected and motivated to engage empathetically with patients, their families, yet how different components of empathy, coping traits interact to shape psychological responses remains unclear. This study examined these relationships in medical, nursing students to inform tailored educational interventions METHODS: Participants who completed two surveys 2 years apart (30 medical students and 88 nursing students) were included. Empathy traits were assessed using the Interpersonal Reactivity Index, coping traits using the Brief Coping Orientation to Problems Experienced Inventory, and psychological responses using the Professional Quality of Life Scale. Mixed-effects models for repeated measures analyzed the impact of empathy and coping traits. Latent profile analysis (LPA) classified participants by empathy and coping traits. Personal distress was significantly associated with increased secondary traumatic stress (STS) and burnout, and decreased compassion satisfaction. Empathic concern was associated with increased compassion satisfaction. Active coping and support seeking were associated with increased compassion satisfaction and reduced burnout, whereas indirect coping was associated with increased STS and burnout. LPA identified three distinct profiles of empathy and coping traits, showing significant differences in psychological responses. Differences in empathy and coping traits influence psychological responses in medical and nursing students. Tailored interventions that consider these traits may be more effective. Show less

Coronary artery anomalies are rare both in coronary angiogram and computed tomography angiography. Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. The phenotype of HCM associated with anomalous coronary origin is not commonly seen especially in children. We describe a case series of two children with HCM combined right coronary artery (RCA) originated from left coronary sinus. Case 1 was a 9-month-old female with HCM coexisted with anomalous origin of RCA has different clinical presentation, and it maybe due to different gene mutation. Show less

This paper presents the Assimilation Modified Emotional (AME) algorithm, which is an enhanced version of the traditional label propagation algorithm (LPA) designed to address key challenges in social network analysis and emotional feature extraction. Traditional LPA methods, such as asynchronous label propagation and the Louvain algorithm, do not incorporate emotional representations and are often limited by local structural dependencies. The AME algorithm addresses these limitations by applying spectral algorithms, Markov chains, graph coarsening, and link prediction to simulate and optimize emotional transitions within the network. In addition, the AME algorithm enhances label representation through multi-label encoding, which allows for more accurate simulation of dynamic emotional states. Experimental results show that the AME algorithm achieves better performance than traditional LPA methods in terms of both accuracy and loss values. These findings indicate that the AME algorithm has strong potential for improving AI models used in social network analysis and emotional feature extraction. Show less

Left ventricular non-compaction (LVNC) can be observed as a phenotypic trait in patients with dilated cardiomyopathy. Familial cases have been increasingly recognized, with sarcomeric gene mutations-particularly in We report a 7-year-old girl with a clinical diagnosis of dilated cardiomyopathy with LVNC since infancy. Genetic analysis revealed two heterozygous missense variants in sarcomeric genes associated with inherited cardiomyopathies: This report highlights the clinical relevance of identifying digenic sarcomeric variants in paediatric cardiomyopathy, particularly when associated with a positive maternal history of PPCM. Familial evaluation and recognition of genotypic overlap may aid in risk stratification and management. Show less

Community-acquired pneumonia (CAP) is still a leading cause of death due to infection globally, yet precise severity assessment remains a significant clinical problem. More than any other group of cytokines, interleukins are central to the regulation of inflammation and shed light on this intricate pathology. In the present review we summarize the biological and clinical characteristics of some of the principal interleukins (ILs) in CAP, classified primarily according to their physiological activity as pro-inflammatory (IL-2, IL-6, IL-8 and IL-12), anti-inflammatory (IL-7, IL-10 and IL-37), dual-action (IL-4 and IL-17), and emerging factors (IL-3, IL-27 and IL-33). Additionally, recent multimodal approaches are discussed such as combining cytokines with organ dysfunction parameters (MR-proADM) or revealing host-response patterns to inform antibiotic and corticosteroid management. We propose that the field needs to transition to immunological endotyping, multi-omics (integrating genetics and lung microbiome), and artificial intelligence (AI) models based on dynamic patient data to achieve precision medicine in CAP management. Show less

This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HFD, n = 30). After 8 weeks of HFD feeding, 24 obese rats were further randomised into three subgroups: HFD (H, n = 8), HFD + moderate-intensity training (HMT, n = 8), and HFD + HIIT (HHT, n = 8). The HMT and HHT groups underwent 8 week training interventions (six sessions/week). The HMT protocol included a 10 min warm-up (treadmill speed: 10 m/min), a 40 min moderate-intensity aerobic phase (60%-70% of maximum speed), and a 10 min recovery (10 m/min). The HHT protocol featured 10 min warm-up and recovery phases (10 m/min), with 40 min of alternating treadmill training: 3 min at 50% maximum speed followed by 3 min at 90% maximum speed. No significant differences in body weight were observed between the HHT and HMT groups. HHT rats displayed significantly lower plasma triglyceride levels than H and HMT rats. Compared with HMT, HHT reduced adipose mass and adipocyte size and increased mitochondrial succinate dehydrogenase and cytochrome c oxidase (COX) activities in adipose tissue. However, HHT rats displayed lower COX activity in visceral white adipose tissue than HMT rats. Training upregulated browning-related genes and uncoupling protein 1 (UCP1) in adipose tissue, with stronger effects in HHT than in HMT. Plasma and adipose tissue IL-27 levels, as well as p38 MAPK-PGC-1α signalling pathway activation, were significantly elevated in both training groups, with greater increases in HHT. HIIT promotes adipose tissue browning by activating the IL-27 signalling pathway and ameliorates obesity-associated metabolic disorders more effectively than MAIT, supporting its potential as a therapeutic strategy for obesity. Show less

Diabetic nephropathy (DN) is a major complication of type 1 diabetes (T1D). Current diagnostic parameters, such as albuminuria and estimated glomerular filtration rate (eGFR), often detect the disease at advanced stages, promoting the identification of additional inflammatory markers. This study investigated the potential roles of pro-inflammatory interleukin-26 (IL-26), anti-inflammatory interleukin-35 (IL-35), and Signal Transducer and Activator of Transcription 1 (stat1) gene expression as potential biomarkers of DN in T1D. To evaluate serum levels of IL-26 and IL-35 and the gene expression of stat1 in T1D patients with and without renal dysfunction to assess their involvement in DN. This case-control study included 80 T1D patients (subgrouped to nephropathy status) and 60 healthy controls. Serum cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and stat1 expression in the blood was assessed using quantitative real-time PCR (qPCR). Statistical analyses included ANOVA, correlation tests, and receiver operating characteristic (ROC) curve analysis. IL-26 levels were not significantly elevated in hemodialysis T1D patients. IL-35 levels were significantly higher in T1D patients with nephropathy and in those on hemodialysis. A significant positive correlation was observed between IL-26 and IL-35 levels (r = 0.561, p = 0.0002). stat1 gene expression was significantly elevated in all T1D subgroups compared to controls, with the highest level observed in the hemodialysis group. ROC analysis indicated that stat1 had a discriminative ability for T1D, whereas IL-35 showed an acceptable diagnostic value for end-stage renal disease. This study showed that stat1 expression and IL-35 levels were linked with renal impairment in the T1D context, with stat1 expression elevated across T1D subgroups, and IL-35 expression was more accentuated in advanced renal dysfunction. Despite its limited discriminative value, IL-26 correlates with IL-35, suggesting simultaneous regulation within the inflammatory microenvironment. Show less

Recent years have seen rapid progress in biological treatments for genetic diseases, as well as conditions like type 1 diabetes that lack an obvious genetic component. The authors sought to explain why this progress has emerged at this particular moment. The best way to illustrate this is by showcasing a wide range of therapies targeting diverse diseases. This progress has been driven by technological advances in genetically modified CAR-T and CAR-NK cells (e.g., using CRISPR or transgenes), which have led to significant improvements in cancer therapy. A key trend now is the emergence of "off-the-shelf" approaches aimed at generating cellular therapies compatible with a range of recipients by mitigating alloreactivity and immune rejection. Different diseases impose distinct biological and logistical limitations; thus, treatment of each patient requires an appropriate strategy. Emerging advances include the modification of therapeutic cells, either ex vivo or in vivo. Current options for transgene delivery mainly comprise lipid nanoparticles (LNPs), adeno-associated virus (AAV) vectors, and lentiviral vectors. Researchers also focus on selecting suitable promoters for specific expression in selected cell types. Altogether, these advances have led to remarkable progress in treating various diseases in recent years. This publication discusses the development of biological therapies, with particular emphasis on cell and gene therapies, illustrated by viable examples across various disorders. It covers implemented solutions for several types of cancer, as well as selected hereditary diseases and syndromes, including Huntington's disease, carbamoyl phosphate synthetase 1 (CPS1) deficiency, hemiplegia, epidermolysis bullosa, chronic granulomatous disease, and congenital deafness. Emerging applications in heart diseases and diabetes are also summarized, along with therapeutic strategies involving tRNA gene editing. Although numerous strategies exist, only the most representative, practical, and up-to-date examples are emphasized. Show less

This study examined the heterogeneous nature of dual-career stress and its asymmetric associations with on adolescent athletes, aiming to: (1) identify distinct stress profiles based on academic, training, and role-conflict stressors; (2) assess whether stress associations vary across levels of athletic burnout and academic performance; and (3) test whether stress profiles moderate these relationships. A two-wave longitudinal study included 843 adolescent male football players in China. Latent Profile Analysis (LPA) categorized participants using three stressor subscales at Time 1. Quantile Regression (QR) at Time 2 (6 months later) analyzed the association between total stress and athletic burnout and academic performance across five quantiles (τ = 0.10-0.90), with stress profile as moderator, controlling for social support, time management, and demographics. LPA revealed four profiles: Balanced Moderates (37.2%), Academically Overwhelmed (28.1%), Sport-Centric Strained (22.0%), and Dual-Track Distressed (12.7%). QR showed the positive association between stress and burnout increased across quantiles (β = 0.41 at τ = 0.10 to 0.78 at τ = 0.90), with the strongest association observed among already burnt-out athletes most. For academic performance, the negative association between stress and performance was strongest at lower quantiles (β = -0.71 at τ = 0.10) and weaker at higher quantiles (β = -0.29 at τ = 0.90). Stress profiles significantly moderate these relationships: the Dual-Track Distressed profile showed the strongest association with on burnout (β = 0.89), while Academically Overwhelmed and Dual-Track Distressed profiles showed the strongest negative association with on academic performance (β = -0.79 and -0.92, respectively). Dual-career stress experiences and impacts are highly heterogeneous. Adolescents cluster into meaningful stress profiles, and stress is most strongly associated with negative outcomes among those already at extremes of burnout or poor academic performance. Findings underscore the need for personalized interventions tailored to athletes' specific stress profiles and outcome levels, supporting holistic development in dual-career contexts. Show less