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Japanese Encephalitis (JE) remains a serious health threat with limited treatment options. This study aims to construct comprehensive libraries of high-frequency compounds from Chinese herbs and to screen active compounds against JE by integrating bioinformatics, network pharmacology, and experimental validation. A natural compound library was constructed through data mining and frequency analysis of Traditional Chinese medicine (TCM) prescriptions for the treatment of JE. ADMET prediction was performed to select compounds with Blood-Brain Barrier (BBB) permeability and to assess their potential toxicity. The compound-JE intersection targets were used to establish a PPI Network and to perform GO and KEGG enrichment analysis. Core targets were identified based on the PPI network by Cytoscape software. Molecular docking was performed with Discovery Studio software. Finally, in vitro experiments were carried out further to screen and validate the anti-inflammatory and antiviral effects of the active compounds in Neuro2a or BV2 cell models infected with Japanese Encephalitis Virus (JEV). Seven of the most commonly used herbs and 16 compounds were identified. Six compounds with BBB permeability and good druggability were screened. Network pharmacology revealed that these six compounds mainly targeted five core targets to exert anti-neuroinflammatory activity. In addition, molecular docking results suggested that JEV proteins were the major targets for these six compounds for antiviral activity. In JEV-induced cell models, Caryophyllene oxide, Qingdainone, and Isoliquiritigenin reduced inflammatory factors by regulating the PTGS2/NF-κB pathway in BV2 cells and exhibited the highest antiviral activity through JEV proteins in Neuro2a cells. This study establishes an integrative strategy bridging traditional medicine with modern pharmacology for anti-JEV drug discovery. The identification of Caryophyllene oxide, Qingdainone, and Isoliquiritigenin as dual-function agents, exerting both antiviral and anti-inflammatory effects, highlights the therapeutic potential of multi-target compounds against JE. Notably, this dual mechanism offers advantages over conventional singletarget therapies by simultaneously inhibiting viral replication and modulating host inflammation. Collectively, this work provides a framework for identifying multi-target anti-JEV agents from natural products, laying a foundation for the translational development of Caryophyllene oxide, Qingdainone, and Isoliquiritigenin. An integrative pipeline combining TCM-based compound library construction, bioinformatics, network pharmacology, and experimental validation has been established to identify novel anti-JE agents. Using this strategy, Caryophyllene oxide, Qingdainone, and Isoliquiritigenin were selected as candidates possessing a unique dual antiviral and anti-inflammatory mechanism for the treatment of JE.
Photoaging is a form of premature skin aging mainly induced by long-term exposure to ultraviolet exposure. Lysosomes are key organelles responsible for the degradation and recycling of intracellular components and are essential for maintaining metabolic and nutrient homeostasis. Although lysosomal dysfunction is closely associated with cellular aging, the role of V-ATPase in regulating lysosomal function during photoaging remains incompletely understood. By screening a V-ATPase-targeted siRNA library and validating the results using publicly available single-cell transcriptomic datasets, we identified ATP6V1A as a key regulator of UVB-induced cellular senescence. Furthermore, ATP6V1A knockdown exacerbated the UVB-induced cellular senescence and impaired lysosomal acidification and membrane integrity, whereas ATP6V1A overexpression effectively alleviated keratinocyte senescence, lysosomal dysfunction and autophagy inhibition. Moreover, treatment with the V-ATPase inhibitor BafA1 aggregated cellular senescence phenotype and autophagy inhibition and this phenomenon partially reversed by ATP6V1A overexpression. Collectively, ATP6V1A promotes autophagy by regulating lysosomal function, thereby relieving UVB-induced cellular senescence.
Large language models may efficiently develop Regular Expression (regex)-based natural language processing for electronic health record phenotyping. We present PromptNLP to assess feasibility by evaluating performance and generalizability to clinical notes across multiple institutions. Sleep-related clinical notes from Kaiser Permanente Southern California, Beth Israel Deaconess Medical Center, and Emory University were used to extract apnea-hypopnea index and Epworth Sleepiness Scale. PromptNLP involves two steps: (1) build an apnea-hypopnea index/Epworth Sleepiness Scale phrase library ("Targeted" via manual, "General" via large language models); (2) input the library into an large language model with prompts to generate regex. For model development (Phase 1), we compared PromptNLP regexes with manual regex. For external validation (Phase 2), we adapted the Phase 1 Targeted regex to Beth Israel Deaconess Medical Center and Emory notes. For application (Phase 3), we applied adapted the regex to 207 404 Kaiser Permanente Southern California notes with validation against 8602 structured apnea-hypopnea index. Phase 1: All Targeted PromptNLP regexes outperformed manual regex for recall (apnea-hypopnea index: 95%-96% vs 80.8%; Epworth Sleepiness Scale: 98%-100% vs 88%; p < .05). General regexes surpassed manual, but with lower recall. Phase 2: Direct Beth Israel Deaconess Medical Center application performed poorly (apnea-hypopnea index/Epworth Sleepiness Scale: 30%/12%), but adapting the phrase library improved recall to 96%/84%. For Emory, recall improved from 85%/86% to 94%/89% after adaptation. Across Phases 1 and 2, the PromptNLP regexes achieved 100% precision. Phase 3: 8216 (95.5%) apnea-hypopnea index values were correctly extracted with 99.8% precision. PromptNLP demonstrated feasibility as an efficient, accurate, and generalizable method, outperforming manual approaches and enabling iterative cross-system improvement. Systematic comparisons to direct large language model approaches are needed.
This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence. According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software. Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration. This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.
Acute kidney injury (AKI) is a life-threatening complication of acute pancreatitis (AP), significantly increasing mortality and extending hospital stay. Early identification of high-risk patients is crucial for timely intervention yet remains clinically challenging. Although several prediction models have been developed, their methodological quality, predictive performance, and clinical applicability vary greatly and lack comprehensive evaluation. A systematic synthesis of existing evidence is therefore imperative to inform clinical practice and guide future research. Two reviewers examined Chinese databases (including CNKI, VIP, SinoMed, and Wanfang), along with PubMed, Web of Science, the Cochrane Library, Embase, and Scopus, to identify risk prediction models for AKI in patients with AP published from inception to December 2025. Two reviewers independently reviewed the literature, retrieved relevant information, and evaluated the risk of bias using the PROBAST tool. The main performance measures of the models, including AUC, calibration, validation method, and predictors, were retrieved. Our review assessed 20 studies with 9481 patients. The prevalence of AKI varied between 13.8% and 72.8%. The reported AUCs of the prediction models ranged from 0.735 to 0.920. All 20 studies were assessed as having high overall risk of bias according to the PROBAST tool, primarily owing to retrospective study designs, lack of external validation, and incomplete model development processes. Existing AKI prediction models for AP patients show moderate to good apparent discrimination but are based on studies with uniformly high risk of bias. No model can be recommended for routine clinical use without prospective external validation.
Edentulous patients often receive mandibular overdentures retained by dental implants; however, the optimal loading protocol (immediate/early vs. delayed loading) for minimizing marginal bone loss (MBL) remains uncertain. This systematic review and meta-analysis aimed to compare MBL between immediate or early loading protocols and delayed loading protocols in two-implant mandibular overdentures. This study was conducted in accordance with PRISMA guidelines. Randomized controlled trials (RCTs) comparing immediate and/or early loading with delayed loading in fully edentulous patients rehabilitated with two-implant mandibular overdentures were included. Non-randomized studies, studies involving partial edentulism, and those with insufficient sample sizes were excluded. A comprehensive search was performed in PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov from January 1990 to April 2025. Risk of bias was assessed using the Cochrane RoB 2 tool. Data were synthesized using a random-effects meta-analysis, with subgroup analyses performed according to implant type, attachment system, and surface characteristics. Twenty-two randomized controlled trials involving 580 patients (296 immediate/early loading; 284 delayed loading) and 1186 implants were included in the systematic review. Of these, 13 studies provided sufficient quantitative data for inclusion in the meta-analysis. Pooled analysis demonstrated that immediate/early loading was associated with significantly lower marginal bone loss compared with delayed loading (WMD = -0.13 mm; 95% CI: -0.23 to -0.03; p = 0.04). However, this difference was small and likely not clinically meaningful and may fall within the range of radiographic measurement variability. Subgroup analysis showed that early loading was associated with greater reduction in MBL compared with delayed loading (WMD = -0.24 mm; 95% CI: -0.44 to -0.05), whereas immediate loading alone showed no significant difference. Bone-level implants and Locator attachments were associated with more favorable outcomes, while effects of surface treatment were inconsistent. Substantial heterogeneity was observed across studies, and the certainty of evidence (GRADE) was low to moderate due to risk of bias, inconsistency, and potential publication bias. Immediate and early loading protocols demonstrate similar clinical performance to delayed loading in terms of marginal bone preservation. Although a small statistically significant difference was observed, the effect size is unlikely to be clinically meaningful. The certainty of evidence is limited, and findings should be interpreted with caution due to heterogeneity and risk of bias across included studies.
Constipation is a common symptom among people with neurodegenerative diseases (PWND), with prevalence ranging from 25.2% to 70%. This is linked to cognitive decline, poor quality of life (QOL), and reduced survival. Although various non-pharmacological interventions exist, their methods and effects are inconsistent, highlighting the need to map current evidence. This scoping review aimed to systematically map evidence on non-pharmacological interventions in PWND, identify gaps, and provide recommendations for future research. A bibliographic search of PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library was conducted in March 2026 without date restrictions. Studies on non-pharmacological interventions for constipation in PWND were included. Of 2,024 identified studies, 13 were included. The included studies targeted people with multiple sclerosis (n = 7), Parkinson's disease (n = 5), and dementia (n = 1), using various diagnostic criteria for constipation. The most frequently used non-pharmacological interventions were abdominal massage (n = 4) and acupuncture (n = 4), followed by biofeedback (n = 2), bowel training (n = 1), foot reflexology (n = 1), and ginger supplementation (n = 1). The type, provider, duration, and frequency of each intervention varied across studies. Improvements were observed in constipation-related outcomes (n = 10), disease-related outcomes (n = 2), QOL outcomes (n = 3), and other outcomes (n = 3), with diverse measurement tools and findings reported. Non-pharmacological interventions may improve constipation and overall well-being in PWND. However, heterogeneity in protocols highlights the need for standardized, disease-specific, nurse-led approaches to support clinical integration. The review protocol was registered in the Open Science Framework (https://osf.io/tu7k3).
Obesity is a complex condition encompassing behavioral, psychological, and physiological factors, frequently associated with elevated mental health burden. Digital Mental Health Interventions (DMHIs) have emerged as promising tools to enhance accessibility, personalization, and scalability of psychological care in obesity management. However, evidence on their effectiveness across delivery modalities and outcomes remains fragmented. This systematic review aimed to evaluate the effectiveness of DMHIs on obesity-related clinical, behavioral, and psychological outcomes; examine whether specific delivery modalities are differentially associated with particular outcomes; and identify methodological gaps to guide future research and implementation. A systematic search was conducted in PubMed, Scopus, PsycINFO, Cochrane Library, Web of Science, and Google Scholar. The review followed PRISMA guidelines, applying rigorous inclusion criteria and independent screening by two reviewers. Quality appraisal was performed using the Cochrane Risk of Bias Tool (RoB 2.0), and studies rated as high risk of bias were excluded. Due to heterogeneity in study design and outcomes, data were synthesized narratively, and no claims of statistical superiority between modalities were made. Thirty-eight randomized controlled trials were included. DMHIs effectively targeted behavioral and psychological aspects of obesity when based on evidence-based psychotherapeutic frameworks - often independently of weight-related improvements. No single delivery format emerged as universally superior; rather, each modality appeared to serve distinct therapeutic purposes. Outcomes were more favorable in interventions that incorporated human guidance, although this finding should be interpreted cautiously because of heterogeneity and the absence of meta-analytic comparisons. Digital mental health approaches-particularly when integrated into stepped-care or hybrid models-represent scalable, person-centered strategies to improve both physical and emotional well-being in adults with obesity.
Depression in children and adolescents is a growing public health concern with lasting effects on mental and physical health. Exercise is a promising strategy for prevention and treatment; however, the comparative effectiveness of different exercise types and their doses response remains unclear. This study aimed to evaluate the effects of different exercise types on depressive symptoms and to explore their dose-response relationships using a network meta-analysis. Six databases (APA PsycInfo, Cochrane Library, Embase, PubMed, Scopus, and Web of Science) were systematically searched, supplemented by Google Scholar and citation tracking. Randomized controlled trials involving exercise interventions in children and adolescents were included. Risk of bias was assessed using the Revised Cochrane Risk of Bias tool. Bayesian network meta-analyses and dose-response analyses were conducted using random-effects models. A total of 41 trials with 4,563 participants were included. Mind-body exercise (MBE) was associated with the largest estimated reduction in depressive symptoms (SMD = - 1.46, 95% CrI: -2.00 to - 0.88), followed by resistance training (SMD = - 0.90, 95% CrI: -1.68 to - 0.14), aerobic exercise (AE; SMD = - 0.80, 95% CrI: -1.20 to - 0.43), interval training (SMD = - 0.60, 95% CrI: -1.43 to 0.24), and combined aerobic exercise and resistance training (AE + RT; SMD = - 0.54, 95% CrI: -1.24 to 0.13). Subgroup analyses suggested relatively larger estimated effects for AE in clinical populations and MBE in subclinical and healthy populations. Age-related differences were also observed, with AE showing relatively larger estimated effects in children and MBE in adolescents. A nonlinear U-shaped dose-response relationship was identified, with the greatest estimated effects occurring at 947 MET-min/week. Dose-response patterns varied across types, ranging from 690 MET-min/week for AE + RT to 1,130 MET-min/week for MBE. Exercise appears to be associated with reductions in depressive symptoms in children and adolescents, although the magnitude of benefit may vary by exercise type and dose. The primary, subgroup and dose-response findings should be interpreted cautiously because of substantial between-study heterogeneity, residual uncertainty, and the overall low-to-moderate certainty of the evidence. Further high-quality studies are needed to strengthen the evidence base, confirm subgroup and dose-response findings, and assess long-term sustainability. Not applicable.
Resistance training is widely utilized to enhance motor performance in healthy populations. Its effects arise not only from peripheral muscular adaptations but also from neuroplastic changes within the central nervous system. Transcranial magnetic stimulation enables noninvasive quantification of corticospinal excitability; however, existing evidence in apparently healthy adults lacks systematic synthesis. This systematic review and meta-analysis aimed to evaluate the effects of resistance training on corticospinal excitability and motor performance in healthy adults. Following the PRISMA 2020 guidelines, a comprehensive search was performed in Web of Science, PubMed, Embase, Cochrane Library, SPORTDiscus, Scopus, and China National Knowledge Infrastructure databases, with the cutoff date of February 27, 2026. Randomized trials were included if they involved healthy adults, with the experimental group receiving resistance training and the control group receiving sedentary activity or no exercise intervention. Data extraction and risk-of-bias assessment using the Cochrane tool were conducted independently by two researchers. Statistical analyses were performed using R software with a random-effects model to compute standardized mean differences (SMDs) with 95% confidence intervals (95% CI), accompanied by heterogeneity testing and publication bias evaluation. Eleven studies encompassing 244 healthy adults were included. Meta-analysis demonstrated that resistance training significantly increased corticospinal excitability (SMD = 0.59, 95% CI [0.10, 1.08], p = 0.003; I² = 69.3%) and significantly improved motor performance (SMD = 0.40, 95% CI [0.02, 0.79], p = 0.04; I² = 64.8%). The included studies were of high methodological quality (mean Cochrane score 6.4), and funnel plots indicated a low risk of publication bias. Resistance training significantly enhances corticospinal excitability and improves motor performance in healthy adults. These findings affirm resistance training as an effective modality for inducing central neural plasticity and furnish an evidence-based foundation for the development of precision training prescriptions. Future research should further elucidate the dose-response relationships between specific training parameters and neural adaptations.
Digital Social Prescribing (DSP) represents an innovative paradigm that integrates digital technologies into traditional social prescribing frameworks to address the social determinants of health (SDOH). However, persistent conceptual inconsistencies and a paucity of theoretical clarity have constrained its systematic application and evaluation within public health and nursing practices. This study aims to clarify the definition of digital social prescribing, distinguish it from traditional social prescribing, and identify its core characteristics through a systematic concept analysis. The Walker and Avant concept analysis framework was adopted. A comprehensive literature searches was conducted across multiple databases, including PubMed, CINAHL (EBSCOhost), APA PsycArticles, Scopus, Web of Science, Embase, IEEE Xplore, ACM Digital Library. A total of 30 relevant articles were included in the analysis. The analysis followed eight steps proposed by Walker and Avant: selecting concept, determining purposes of the analysis, identifying all uses of concept, determining defining attributes, constructing model and related cases, identifying antecedents and consequences, and defining empirical referents. Digital social prescribing (DSP) is not merely a technological tool but a multidimensional public health model. Its five defining attributes are the uses of technology, non-clinical services, make personal plans based on needs, likes and location, community-based resources, and organizations from different sectors. The antecedents of DSP include contextual and population health drivers, medical systems and structural limitations, technological enabling factors, practice and implementation gaps and catalytic events and social development trends. The consequences of DSP encompass health and well-being outcomes, care and service delivery, system and implementation outcomes, equity and ethical considerations. Despite its potential benefits, DSP also faces challenges, including digital exclusion, data governance issues, gender imbalances and structural ethnic disparities. This study provides a comprehensive conceptual framework for digital social prescribing (DSP), addressing existing conceptual ambiguities and clarifying its theoretical boundaries. The study also highlights the need to critically address potential challenges associated with DSP implementation, including digital exclusion, data governance concerns, gender imbalances and structural ethnic disparities. These findings support the development of standardized evaluation frameworks and provide guidance for future research, practice and policy aimed at facilitating the sustainable and equitable implementation of DSP.
IntroductionCrohn's disease (CD) is a complex disease with rising incidence that is usually treated with medical management. However, surgery plays an important role for medically refractive cases, or Crohn's related complications. New techniques such as extended mesenteric excision (EME), and Kono-S anastomosis (KSA) are being increasingly adopted. However, their potential for reducing CD recurrence remains unclear.MethodStudies were identified through searching Medline, Embase, Cochrane Library and JBI EBP from database inception to January 2025. Studies where patients with CD had intestinal resection and underwent at least two of four interventions being KSA, other anastomosis, EME and/or limited mesenteric excision (LME) were included. Two investigators independently identified studies and abstracted data. RCT quality was assessed using Cochrane Risk of Bias 2 tool and cohort study quality assessed using Newcastle Ottawa Scale. The study adhered to PRISMA guidelines. Bayesian network meta-analysis was conducted to assess risk of surgical and endoscopic recurrence at 5 years and 6-12 months respectively.ResultsThirteen studies composed of 3 RCTs and 10 cohort studies (n = 2,044) were included, assessing surgical and/or endoscopic recurrence after KSA, other anastomosis, EME or LME. There was statistically significant reduction in surgical recurrence in KSA compared to other anastomosis (odds ratio 0.07, 95% credible interval) but not EME compared to LME. There was no difference in endoscopic recurrence in any groups.ConclusionKSA was associated with reduced surgical recurrence compared with other anastomosis, but not endoscopic recurrence. There were insufficient studies to support similar improvement in recurrence in EME over LME.
HER2-positive gastric and gastroesophageal junction (GEJ) cancers have poor prognosis despite standard trastuzumab-based chemotherapy. Immune checkpoint inhibitors (ICIs) may enhance therapeutic efficacy when combined with trastuzumab. A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and Scopus were searched up to December 29, 2025. Studies evaluating ICIs plus trastuzumab and chemotherapy versus trastuzumab-based therapy alone were included. Kaplan-Meier curves were digitized using WebPlotDigitizer and reconstructed to individual participant data (IPD). Pooled survival outcomes, objective response rate (ORR), disease control rate (DCR), and safety were analyzed. Six studies including 1,097 patients were included. ICIs plus trastuzumab and chemotherapy significantly improved median progression-free survival (10.4 vs. 8.27 months; HR 0.6951, p<0.0001) and overall survival (20.4 vs. 17.2 months; HR 0.8104, p=0.004) compared with control. ORR (OR 1.85, p<0.00001) and DCR (OR 2.46, p=0.006) were also superior. Grade ≥3 adverse events were similar between groups. ICIs combined with trastuzumab and chemotherapy improve survival and response rates in HER2-positive gastric/GEJ cancers with manageable toxicity, supporting their integration into treatment strategies. https://www.crd.york.ac.uk/prospero/, identifier CRD420261280958.
Predicting patient-specific neurodegenerative trajectories is essential for targeted interventions in Alzheimer's disease. Although the APOE-ε4 allele is the predominant genetic risk factor for hippocampal atrophy, whether its structural impact reflects a static developmental phenotype or an accelerated neurodegenerative process conditional on amyloid pathology remains unresolved. To quantify the effect of APOE-ε4 on hippocampal volume via cross-sectional meta-analysis, and to validate the gene-dose effect through independent longitudinal modeling in two cohorts. Original observational neuroimaging studies reporting hippocampal volume stratified by APOE genotype in human participants across the Alzheimer's disease continuum. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2025. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. The meta-analysis included 18 studies (N = 4, 311) and indicated reduced hippocampal volume in carriers (ICV-corrected stratum: SMD = -0.41, 95% CI [-0.67, -0.16], p = 0.004; I 2 = 74.0%), with the effect absent in uncorrected analyses. Longitudinal gene-dose models, run independently in the post-QC NACC LMM sample (N = 3, 239; imaging extraction N = 3, 248) and ADNI (N = 1, 150) cohorts and combined via fixed-effect meta-analysis, demonstrated a dose-dependent acceleration of hippocampal atrophy: homozygotes exhibited a pooled additional volume loss of -58.25 mm3/year (95% CI [-89.26, -27.23], p = 2.33 × 10-4; I 2 = 0%) and heterozygotes -34.32 mm3/year (95% CI [-52.31, -16.32], p = 1.85 × 10-4) relative to non-carriers. Biomarker-stratified analyses used baseline-only CSF measurements subject to time-varying confounding and should be interpreted as exploratory. Moderate between-cohort heterogeneity was observed for the heterozygote effect (I 2 = 63.0%). These findings provide two-cohort evidence for a dose-dependent APOE-ε4 effect on hippocampal atrophy rates. Exploratory biomarker-stratified analyses in ADNI suggest this acceleration may be conditional on amyloid-β positivity, a hypothesis requiring validation with time-varying causal models. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251243460, PROSPERO: CRD420251243460.
Previous meta-analyses often lacked explicit time and included heterogeneous case types and surgical strategies. This led to substantial heterogeneity and limited the clinical applicability of these meta-analyses. This study focuses on evidence from the past 15 years, systematically comparing percutaneous pedicle screw fixation (PPSF) with open pedicle screw fixation (OPSF) for unstable traumatic thoracolumbar fractures (TTF). We aim to evaluate perioperative outcomes and radiographic correction based on contemporary practice. Randomized controlled trials (RCTs) published in English between January 2011 and January 2026 were retrieved from PubMed, Embase, the Cochrane Library, and the Web of Science Core Collection. Studies were screened using predefined inclusion and exclusion criteria. Six RCTs involving 305 patients were included, with 151 patients in the experimental group and 154 in the control group. Meta-analysis was performed using Review Manager 5.4. Mean difference (MD) was used as the effect size. Heterogeneity was assessed with the I2 statistic. Sensitivity analysis was used to identify the main source of heterogeneity. Publication bias was evaluated using Egger's test. The random-effects meta-analysis showed that the experimental group had significantly less intraoperative blood loss (MD = - 32.51 mL, 95% CI - 57.52 to - 7.51, P = 0.01), shorter postoperative hospital stay (MD = - 2.09 d, 95% CI - 3.89 to - 0.29, P = 0.02), and smaller postoperative Cobb angle (MD = - 1.06°, 95% CI - 1.67 to - 0.46, P < 0.001). There was no significant difference in operative time (MD = - 10.15 min, 95% CI - 28.75 to 8.46, P = 0.29) or postoperative vertebral wedging angle (MD = 0.25°, 95% CI - 1.73 to 2.24, P = 0.80) between groups. Sensitivity analyses identified the study by Yang et al. as the main source of heterogeneity for operative time. After excluding this study, the fixed-effects model showed a shorter operative time in the experimental group (MD = - 8.85 min, 95% CI - 12.74 to - 4.95, P < 0.001). Perioperative outcomes showed high heterogeneity, whereas radiographic outcomes showed low to moderate heterogeneity. Egger's test indicated no significant publication bias. Risk-of-bias assessment classified four RCTs as having a low risk of bias and two as having some concerns; no study was judged to have a high risk of bias. PPSF may offer perioperative advantages over OPSF in selected unstable traumatic thoracolumbar fractures, mainly by reducing visible intraoperative blood loss and shortening postoperative hospital stay. PPSF was also associated with a modestly smaller postoperative segmental Cobb angle, although its clinical relevance and long-term durability remain uncertain. The operative-time finding should be interpreted cautiously because it became significant only in exploratory sensitivity analysis.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuro-autoimmune disease. Monoclonal antibodies targeting B cell antigens CD19 and CD20, the interleukin-6 receptor, or the complement cascade are used as preventive therapies to reduce relapse rates. We conducted a network meta-analysis (NMA) to compare the effect of rituximab on time to first relapse with ravulizumab, eculizumab, inebilizumab, and satralizumab in patients with NMOSD who are aquaporin-4 (AQP4)-IgG-positive. A systematic search was conducted in PubMed, Scopus, CINAHL, EMBASE, Web of Science, the Cochrane Library, and gray literature sources up to October 31, 2024, and updated on November 1, 2025, following PRISMA guidelines. A network meta-analysis of randomized and open-label trials was conducted to compare time to first relapse between rituximab and other monoclonal antibody therapies. From 6337 records, 3825 duplicates were removed; 2512 were screened, 2327 excluded, leaving eight trials. The prior treatment, relapse history, and definitions and adjudication of relapse varied across studies. Rituximab showed higher hazard ratio (HR) point estimates for time to first relapse compared with ravulizumab with or without immunosuppressive therapies (IST) (HR 5.00, 95% CI 0.25, 101.01) and eculizumab ± IST (HR 1.17, 95% CI 0.12, 10.89), but were lower compared with satralizumab ± IST (HR 0.29, 95% CI 0.04, 2.23). In patients not receiving IST, rituximab showed numerically higher HR compared with ravulizumab (HR 3.33, 95% CI 0.13, 83.16) and eculizumab (HR 1.59, 95% CI 0.05, 50.17), but lower point estimates compared with inebilizumab (HR 0.31, 95% CI 0.04, 2.31) and satralizumab (HR 0.27, 95% CI 0.03, 2.21). This NMA showed hazard ratio point estimates favoring eculizumab and ravulizumab over rituximab. However, wide, overlapping confidence intervals and between-study heterogeneity indicate substantial uncertainty. Head-to-head trials or registry-based studies are needed to determine the most effective treatment for AQP4-IgG-positive NMOSD.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, behavioral disturbances, and loss of functional independence. As the global prevalence of AD continues to rise, traditional episodic care models are increasingly inadequate for providing continuous and individualized support. Wearable electronic devices offer a potential alternative by enabling non-invasive, real-time monitoring in everyday settings. This systematic review synthesizes current evidence on the applications, reported outcomes, and implementation challenges of wearable and wearable-adjacent technologies in AD care. A systematic literature search was conducted in September 2025 across five databases: PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, using keywords and MeSH terms related to wearable electronic devices, smart glasses, smartwatches, and Alzheimer's disease. The review protocol was prospectively registered in PROSPERO (CRD420251158703). Two independent reviewers screened records and extracted data in accordance with PRISMA 2020 guidelines. Methodological quality was assessed using a validated 10-item appraisal tool. Of 1399 identified records, ten studies met the eligibility criteria. For structured synthesis, the included technologies were organized into four architectural categories: body area network-based sensor systems, augmented reality smart glasses, hybrid wearable-mobile platforms, and wearable-adjacent assistive technologies. Across studies, the included technologies were applied to physiological monitoring, mobility and gait assessment, cognitive and spatial support, and caregiver communication. Findings suggest preliminary feasibility across these domains; however, small sample sizes, heterogeneous outcome measures, and predominantly early-phase study designs limit the strength of available evidence. Current evidence suggests that wearable and wearable-adjacent technologies may contribute to multiple aspects of AD care, particularly in home-based settings. Translation into routine practice requires prospective, adequately powered studies with standardized outcome frameworks, alongside regulatory alignment and patient-caregiver co-design to address persistent usability barriers.
Bedside teaching (BST) has declined in the UK despite longstanding educational interventions. We sought to outline current barriers and synthesise experiences of medical students and clinical educators to understand organisational dynamics constraining BST. We conducted a qualitative systematic review following PRISMA 2020, registered in PROSPERO (CRD420251033043). MEDLINE, Embase, CINAHL, and Cochrane Library were searched for 2014 to April 2025. We included UK qualitative or mixed-methods studies on barriers to BST; non-UK studies, reviews, and editorials were excluded. Two reviewers independently screened and appraised studies using the Critical Appraisal Skills Programme (CASP) checklist. Thematic synthesis was performed with line-by-line coding and iterative team discussion. Four interconnected themes emerged: (1) institutional marginalisation of undergraduate teaching (service pressures, limited recognition/resources), (2) educator constraints and professional isolation (limited training/feedback, competing demands), (3) learner unpreparedness and engagement challenges (insufficient exposure and confidence), and (4) patient-related ethical and practical barriers (reluctance, privacy, infection concerns). These themes formed a self-reinforcing organisational cascade that sustains BST decline. Barriers to BST in the UK are systemic rather than isolated, reflecting structural misalignment between service demands and educational priorities. Sustainable improvement requires organisational reform and resourcing that explicitly prioritise bedside teaching within clinical practice, alongside continued investment in the educators who deliver it.
Miyazaki syndrome is a rare and underrecognized complication of long-standing cerebrospinal fluid (CSF) diversion. It usually occurs in patients with chronic CSF overdrainage and is caused by enlargement of the cervical epidural venous plexus, which may compress the spinal cord and cause progressive myelopathy or radiculopathy. Because symptoms develop slowly and may resemble degenerative cervical myelopathy or other neurological conditions, diagnosis is often challenging. We report two illustrative cases from our institution. The first patient was a 57-year-old man with a ventriculoperitoneal (VP) shunt placed at birth for neonatal intraventricular hemorrhage (IVH), who developed progressive spastic paraparesis, sensory ataxia, and increasing wheelchair dependence over several years. MRI showed chronic intracranial hypotension with marked cervical venous engorgement and upper cervical cord compression. He underwent shunt revision with the addition of an anti-siphon device, followed by radiological resolution of venous engorgement and partial clinical improvement. The second patient was a 44-year-old woman with congenital hydrocephalus treated with shunting since childhood, who presented with worsening gait disturbance, recurrent falls, impaired hand coordination, orthostatic headaches, and radicular pain. Imaging showed venous congestion at C2 with cord compression and chronic CSF hypotension. Her shunt was revised with placement of a Codman CERTAS® Plus programmable valve and anti-siphon device (Integra LifeSciences, Princeton, NJ, USA), resulting in improved venous drainage, cord decompression, and meaningful clinical recovery. To place these cases in context, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review - registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251048122) - of case reports and case series on Miyazaki syndrome or overshunting-associated myelopathy through May 2025 using PubMed, the Cochrane Library, and Google Scholar. Study quality was assessed with Joanna Briggs Institute tools, and data were extracted on patient characteristics, shunt type, valve configuration, anti-siphon device use, symptom latency, imaging findings, treatment, and outcomes. Thirty-one studies, including 37 patients, met the eligibility criteria. The mean age was 43.9 years, and VP shunts were the most common shunt type. The most consistent imaging finding was cervical epidural venous plexus engorgement with cord compression, often associated with pachymeningeal enhancement and slit ventricles. The median interval from the last shunt procedure to symptom onset was 14 years, and valve adjustability did not significantly influence this latency. Most patients were treated by correcting CSF overdrainage through valve pressure adjustment, conversion to a programmable valve, and/or addition of an anti-siphon or gravitational device. All patients treated with an anti-siphon device improved, and earlier treatment was associated with better outcomes. These findings emphasize that Miyazaki syndrome should be considered in shunted patients with progressive myelopathy and imaging signs of intracranial hypotension or CSF overdrainage. Early recognition and correction of siphoning through valve optimization and anti-siphon device placement may reverse venous congestion, improve neurological function, and prevent permanent spinal cord injury.
Astrocytes participate in the clearance of obsolete or unwanted neuronal synapses. However, the molecular machinery involved in synapse recognition remains unclear, particularly in pathological conditions. Here, we investigated the phagocytic process of astrocytes through individual gene silencing using a druggable gene library. Our study demonstrates that the Atypical chemokine receptor 3 (Ackr3) is a major player of astrocyte-mediated synapse engulfment. Mechanistically, we showed that Ackr3 recognizes phosphatidylethanolamine (PE)-bound C-X-C motif chemokine 12 (CXCL12) at synaptic terminals, thus serving as a novel marker of synaptic dysfunction. Notably, both ACKR3 and CXCL12 are upregulated in post-mortem brains of Alzheimer's disease (AD) patients, and AD mouse models. Genetic downregulation of Ackr3 in AD mice significantly reduces astrocyte-mediated synaptic elimination and rescues pathological phenotypes, including synapse loss and cognitive impairment. Overall, this work unveils a novel, possibly targetable mechanism of astrocyte-mediated synaptic engulfment implicated in neurodegenerative disease.