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Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: The Asia Pacific region is home to more than half of the world's 1·93 billion adolescents (aged 10-24 years). Addressing adolescent health in this region is of global importance, but to date a systematic analysis of key contributors to disease in adolescents has not been done, which is a barrier to responsive action. This systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 aims to provide a comprehensive assessment of adolescent health across the Asia Pacific region, at both the subregional and national levels, encompassing burden of disease, mortality, and prevalence of adolescent risk factors. METHODS: As part of GBD 2023, we obtained estimates for cause-specific mortality, disability-adjusted life-years (DALYs), and risk factor prevalence by sex for adolescents aged 10-24 years and 5-year age groups (10-14 years, 15-19 years, and 20-24 years) across 44 countries and territories (hereafter referred to collectively as Asia Pacific), grouped by seven UN subregions, from 2000 to 2023. We extracted GBD 2023 population counts and estimates of number and rate (per 100 000 population) for mortality and disease burden (DALYs). Risk prevalence estimates were obtained directly from the Institute for Health Metrics and Evaluation, and binge drinking estimates were sourced from WHO. Estimates are reported with 95% uncertainty intervals (UIs) where possible. UIs were estimated by running 250 draws of the posterior distribution, ordering the draws, and selecting the 2·5th and 97·5th percentiles for each metric. FINDINGS: In 2023, in adolescents across Asia Pacific, there were 637 496 deaths and a total disease burden of 115·8 million DALYs, representing 34·1% of global adolescent deaths and 40·6% of the global adolescent burden of disease. Non-communicable diseases (NCDs; particularly mental disorders) were the leading causes of disease burden and mortality (64·8% of DALYs and 43·9% of deaths). Unintentional and transport injuries were also leading causes of death (14·7% of deaths due to transport injury and 13·3% of deaths due to unintentional injury) and leading causes of disease burden particularly among males in south-eastern Asia. In Melanesia, Micronesia, and some parts of south-eastern Asia (Cambodia, Indonesia, Laos, the Philippines, and Timor-Leste), respiratory infections and tuberculosis remained important contributors. Southern Asia had the largest reduction (1·5% per year) in all-cause DALYs over the study period, and Australia and New Zealand (0·2% per year) had the smallest, with females in Australia and New Zealand showing a slight increase contrary to regional trends. Eastern Asia had the largest reduction (2·8% per year) in all-cause mortality rate and Melanesia (0·8% per year) the smallest. Risk factors generally had between-subregion and within-subregion variation; however, some regional trends stood out, with overweight and obesity increasing in all countries across the region, and binge drinking increasing in more countries than not. In 2023, prevalence of smoking in males exceeded that in females in every country, from 40% difference in Timor-Leste to less than 1% difference in Australia. Anaemia prevalence is decreasing in all countries, but female prevalence was higher and reducing at a slower rate than in males. Bullying prevalence was slightly higher in Polynesia, Micronesia, and Melanesia combined, Australia and New Zealand, and eastern Asia compared with southern and south-eastern Asian subregions. INTERPRETATION: Several patterns were consistent across the region: the dominance of mental disorders and NCDs, the universal rise in overweight and obesity (particularly high in Oceanic countries but increasing rapidly in south and south-eastern Asia), and persistent sex-specific challenges across subregions: unintentional injuries and smoking in males, and anaemia in females. Actions to tackle shared risk factors (while accounting for context-specific local health profiles, workforce deficits, cultural factors, and health system capacity) should not be forgone due to local variation. Future research could focus on subnational variation, intersecting inequalities, and multi-sectoral interventions targeting shared risk factors. Priority actions should include regional investment in adolescent mental health services and obesity prevention, targeted injury reduction strategies for high-risk populations, and sex-specific approaches to smoking cessation and anaemia reduction, delivered through local health systems with the capacity and cultural responsiveness to meet local needs. FUNDING: Gates Foundation and Australian Government.

Humans

Marked response to dabrafenib plus trametinib in a patient with BRAF V600E-mutant pancreatic hepatoid carcinoma: a case report and systematic analysis of 57 cases.

BACKGROUND: Pancreatic hepatoid carcinoma (PHC) is an extremely rare pancreatic malignancy characterized pathologically by hepatocellular-like differentiation. Some patients may present with elevated serum alpha-fetoprotein (AFP). Owing to the limited number of reported cases, the clinical features, molecular characteristics, and systemic treatment strategies for PHC remain poorly defined. BRAF V600E is an actionable alteration with established therapeutic value in several solid tumors; however, its clinical significance in PHC remains unclear. CASE PRESENTATION: We report the case of a 64-year-old man with advanced PHC who presented with painless jaundice, dark urine, and recent weight loss. Laboratory tests showed marked cholestatic liver injury and significantly elevated AFP. Imaging revealed a pancreatic head-neck mass with portal vein tumor thrombus and regional lymph node metastases, corresponding to cT4N1M1, stage IV disease. Percutaneous transhepatic biliary drainage was first performed to relieve obstructive jaundice. Biopsy of the pancreatic lesion showed poorly differentiated carcinoma. Based on hepatoid morphology, immunophenotype, elevated serum AFP, imaging findings, and exclusion of primary hepatocellular carcinoma, the patient was diagnosed with PHC. Comprehensive genomic profiling identified a BRAF V600E mutation with a variant allele frequency of 31.89%, together with MDM2 and MYC amplification. The molecular profile was characterized by microsatellite stability, low tumor mutational burden, MGMT promoter methylation, and low PD-L1 expression. After two cycles of pembrolizumab-based first-line therapy combined with paclitaxel, S-1, and lenvatinib, AFP continued to increase and imaging showed rapid tumor enlargement, consistent with immune checkpoint inhibitor-related hyperprogressive disease. The treatment was then switched to dabrafenib plus trametinib. AFP declined rapidly and returned to the normal range within approximately two months. Imaging showed marked regression of the pancreatic primary lesion, disappearance of the portal vein tumor thrombus and metastatic lymph nodes, and conversion of peripheral blood minimal residual disease to negative. The best response was partial response. After approximately six months of targeted therapy, occult disease progression emerged. Subsequent addition of cetuximab, replacement of the MEK inhibitor, and dose escalation of targeted therapy did not restore sustained systemic disease control, although local disease remained manageable with subsequent treatment adjustments. Proton radiotherapy was then delivered to the residual pancreatic lesion, followed by CyberKnife radiotherapy for a newly detected 2.3-cm metastasis in the caudate lobe of the liver. As of April 2026, the patient's AFP level remained close to normal at 14 ng/mL, local lesions were well controlled, peripheral blood minimal residual disease had turned positive, and the patient remained in a stable tumor-bearing state. SYSTEMATIC ANALYSIS: We further summarized 57 previously reported cases of PHC. The median age was 54 years, and 66.7% of patients were male. Tumors occurred at different pancreatic sites, including the pancreatic head in 21 cases, body in 8 cases, tail in 13 cases, and multifocal lesions in 15 cases. More than half of the patients had metastatic disease at initial diagnosis. The immunophenotype of PHC was highly heterogeneous. Regarding treatment, 47 patients underwent surgery, 20 received chemotherapy, and 6 received targeted therapy. The 1-year and 3-year overall survival rates were 70.7% and 43.1%, respectively, indicating an overall poor prognosis. CONCLUSION: This case suggests that BRAF V600E may represent a clinically actionable driver alteration in PHC. Dabrafenib plus trametinib induced a rapid and deep response in this patient with advanced BRAF V600E-mutant PHC. Microsatellite stability, low tumor mutational burden, low PD-L1 expression, and MDM2 amplification may be associated with limited benefit from immunotherapy and a risk of hyperprogression. After resistance to targeted therapy, local radiotherapy may serve as an important strategy for controlling oligoresidual and oligometastatic lesions. Together with the literature review, this case supports early comprehensive molecular profiling and individualized multidisciplinary management for advanced PHC.

BRAF V600E

Global, regional, and national prevalence of second-hand smoke and attributable disease burden in 204 countries and territories, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: Second-hand smoke (SHS) exposure remains a major source of morbidity and mortality among non-smokers. This study presents the first dedicated Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) publication to systematically quantify SHS prevalence and evaluate its effect as a global risk factor across a broader range of outcomes. METHODS: Using the GBD 2023 comparative risk assessment framework, we estimated SHS exposure prevalence and attributable disease burden across 204 countries and territories from 1990 to 2023, stratified by age and sex. Exposure estimates were derived by synthesising population-based surveys and household composition data through spatiotemporal Gaussian process regression. Relative risks for nine health outcomes, now including asthma, were estimated using the Burden of Proof methodology, and applied to calculate attributable deaths and disability-adjusted life-years (DALYs). FINDINGS: In 2023, an estimated 2·71 billion (95% UI 2·44-3·02) people worldwide were exposed to SHS, including 767 million (687-858) children aged 0-14 years. Age-standardised prevalence was highest in southeast Asia, east Asia, and Oceania (48·4% [44·0-53·4]), with female individuals in some countries experiencing nearly 1·8 times the exposure prevalence of male individuals. Despite a 22·2% (10·6-32·4) decline in global age-standardised prevalence since 1990, this progress has not been sufficient to reduce the absolute number of exposed individuals, which has remained stable globally and has risen sharply in sub-Saharan Africa (98·5% [62·0-144·4] increase) and North Africa and the Middle East (72·1% [47·8-101·8] increase). In 2023, SHS exposure accounted for 1·66 million (1·33-2·07) deaths and 44·8 million (35·8-54·3) DALYs globally. Ischaemic heart disease was the leading contributor to SHS-attributable DALYs (12·0 million [9·31-15·2]) overall, while lower respiratory infections predominated among children (5·16 million [3·48-7·12]). INTERPRETATION: We estimated that SHS remains a substantial driver of global health loss, particularly through cardiovascular and paediatric respiratory diseases. Persistent geographical disparities and growing absolute numbers of exposed individuals in several regions underscore the urgent need for accelerated implementation and enforcement of comprehensive tobacco control measures, particularly to protect women and children in both public and domestic environments. FUNDING: Bloomberg Philanthropies and the Gates Foundation.

Journal Article

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies.

Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1, and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, previously overlooked role for noncoding snRNAs in human disease. Here, we systematically analysed 200 potentially functional snRNA genes in a French cohort comprising 26,911 individuals with rare disorders and through international collaborations. We identify de novo and biallelic variants in RNU2-2 associated with both dominant and recessive NDDs in 126 individuals from 108 unrelated families. Recessive RNU2-2 NDD is at least twice as frequent as the dominant NDD caused by n.4G>A and n.35A>G, and often arises from a de novo variant in trans with an inherited allele, reflecting the high mutability of snRNA genes. Dominant and recessive RNU2-2-NDDs share overlapping clinical features with frequent epilepsy. Blood transcriptomics and DNA methylation analyses revealed subtle, variant-specific effects on splicing and episignatures. Our findings support a gradient-of-impact model and a continuum between dominant and recessive inheritance, establishing RNU2-2 variants as a frequent cause of NDDs, nearly as prevalent as ReNU syndrome.

Journal Article

Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

Humans

Systematic analysis of the type VII secretion system in Streptococcus gallolyticus subsp. gallolyticus reveals genomic diversity and functional associations.

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathobiont associated with bacteremia, infective endocarditis, and colorectal cancer. However, the genomic diversity of this subspecies and the distribution of key virulence determinants, particularly the type VII secretion system (T7SS), remain poorly characterized. Here, we performed genomic analyses of 76 Sgg strains from diverse geographic and host origins. Core- and pan-genome analyses, multi locus sequence typing, and phylogenetic reconstruction revealed dominant sequence types (STs) that correlate with geographic origin or source of isolation. Furthermore, systematic characterization of the T7SS locus identified five new T7SS subtypes and demonstrated a strong association between T7SS subtype and ST. We further expanded the known repertoire of T7SS LXG domain-containing polymorphic toxins (LXG toxins) in Sgg substantially through genome-wide searches. Distinct distribution patterns were observed for the LXG toxins across the strains. Lastly, our data indicated that T7SS subtype was significantly associated with biofilm formation capacity of Sgg strains. Together, these findings advance our understanding of Sgg genomic diversity, reveal substantial lineage-associated variation in T7SS architecture and effector repertoires, and suggest a previously unrecognized connection between T7SS and biofilm formation in Sgg.

LXG toxins

Systematic Analysis of Tumor Microenvironment Using IOBR.

The Immuno-Oncology Biological Research (IOBR) package is an R-based analysis tool for exploring the tumor microenvironment (TME) and its influence on anti-tumor immunity. Built for high-throughput data-spanning both transcriptomic and genomic profiles-IOBR integrates six analytical modules, including transcriptomic data preprocessing, TME profiling, TME pattern identification, ligand-receptor interaction analysis, genome-TME interaction assessment, and visualization. In this chapter, we walk through a multi-omics workflow using example datasets, illustrating data preparation, distribution analyses, result interpretation, and graphical output. IOBR is open source and is available at https://github.com/IOBR/IOBR and a detailed GitBook ( https://iobr.github.io/book/ ) offers a complete manual and analysis guide for each function.

Tumor Microenvironment

Comparing the efficacy and safety of unilateral versus bilateral spinal anesthesia: a meta-analysis and systematic review.

BACKGROUND: Unilateral spinal anesthesia has gained increasing attention in recent years. Emerging evidence suggests that it provides comparable analgesia to conventional bilateral spinal anesthesia while reducing adverse effects, and its efficacy and safety compared to bilateral spinal anesthesia remains controversial. OBJECTIVE: This systematic review and meta-analysis aims to evaluate and compare the efficacy and safety of unilateral versus bilateral spinal anesthesia. DESIGN: Systematic reviews and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: A systematic search was conducted across PubMed, EMBASE, and Cochrane Library from inception to December 10, 2024. ELIGIBILITY CRITERIA: Included studies were randomized controlled trials involving adult patients (&#x2265;18&#x2009;years) undergoing surgery under spinal anesthesia, comparing unilateral versus bilateral spinal anesthesia for efficacy and adverse effects. Studies that focused exclusively on either unilateral or bilateral spinal anesthesia were excluded. The comparator group used the same local anesthetic as the experimental group, with no restrictions on adjuncts (e.g. fentanyl, morphine). RESULTS: Nineteen randomized controlled trials including 1191 patients met the inclusion criteria. Compared with bilateral spinal anesthesia, unilateral spinal anesthesia has a longer onset of sensory blockade (MD = 2.58, 95% CI: 0.93 to 4.22, p&#x2009;=&#x2009;0.002), a shorter duration of sensory blockade (MD&#x2009;=&#x2009;-27.83, 95% CI: -39.25 to -16.42, p&#x2009;<&#x2009;0.00001). In addition, unilateral spinal anesthesia significantly reduced the incidence of hypotension (RR = 0.40, 95% CI: 0.31 to 0.52, p&#x2009;<&#x2009;0.0001), nausea and vomiting (RR = 0.20, 95% CI: 0.07 to 0.56, p&#x2009;=&#x2009;0.002), and post-dural puncture headache (RR = 0.44, 95% CI: 0.23 to 0.81, p&#x2009;=&#x2009;0.009). No statistically significant differences were observed in bradycardia and urinary retention. Collectively, these findings support unilateral spinal anesthesia as a strategy that may enhance perioperative safety while maintaining adequate anesthetic efficacy in appropriately selected patients. CONCLUSIONS: Unilateral spinal anesthesia may offer a favorable balance between anesthetic efficacy and safety compared with bilateral spinal anesthesia, although its clinical utility may depend on surgical duration and patient characteristics.

Humans

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans

Test-retest reliability of spatiotemporal, kinematic, and kinetic measures in marker-based 3D gait analysis: A systematic review.

BACKGROUND: Marker-based 3D gait analysis (3DGA) is widely used to quantify impairments and evaluate treatment effects. For longitudinal clinical interpretation, clinicians and researchers need reference values for inter-session measurement error. For this purpose, this systematic review synthesized Standard Error of Measurement (SEM) values for spatiotemporal, kinematic, and kinetic (moments) outcomes obtained from marker-based 3DGA studies. METHODS: PubMed and Scopus were searched (final search: 11 December 2025). Studies reporting inter-session test-retest SEM and/or MDC for steady-state overground or treadmill walking using marker-based motion capture were included. Two authors screened records and appraised methodological/reporting quality using a custom tool informed by COSMIN, GRRAS, and biomechanics-specific items. Due to heterogeneity, results were synthesized descriptively using study-level median SEM values, stratified by joint, plane, population (healthy, pathological, single subgroups), and walking condition. Minimal Detectable Change (MDC) values were computed for all available data. RESULTS: Thirty-four studies (762 participants, 44.2% females) were included, with substantially more evidence for overground than treadmill walking. Overground spatiotemporal outcomes showed low errors (walking speed SEM of 0.06 m/s; timing typically &#x2264;0.03 s; spatial parameters generally &#x2264;0.03 m). For joint kinematics during overground walking, median SEMs were 2.4&#xb0; (sagittal), 1.9&#xb0; (frontal), and 3.3&#xb0; (transverse). The corresponding joint-kinetic SEMs were approximately 0.06, 0.04, and 0.03 Nm/kg, respectively. Treadmill data followed similar patterns. SIGNIFICANCE: Marker-based 3DGA allows for accurate assessment of spatiotemporal, kinematic, and kinetic gait features. We provided detailed SEM/MDC lookup tables to support clinical decision-making. Results further offer a benchmark for validating emerging gait assessment technologies (e.g., markerless systems) against realistic limits of marker-based 3DGA.

Humans

A Bibliometric Analysis of Systematic Reviews in the Field of Ankylosing Spondylitis from 2007 to 2025.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease and the most common clinical form of spinal arthritis. Over the past decades, tremendous progress has been made in systematic reviews on AS. This study aimed to conduct a bibliometric analysis of AS-related meta-analyses to visualize the hotspots and trends in the field. METHODS: A comprehensive search was conducted for publications of AS meta-analysis from 2007 to 2025 using the Web of Science Core Collection database. Bibliometric analysis was performed using the Bibliometrix software package, VOSviewer, and CiteSpace. RESULTS: In total, 1073 articles were identified, and the number of relevant publications showed annual growth. China, the USA, and England were the most productive countries. Annals of the Rheumatic Diseases was the most productive journal (54, 10.65%), Pan Faming was the most productive author (23, 4.54%), and Anhui Medical University (45, 8.88%) was the most productive institution. High-frequency keywords were mainly grouped into five themes: complications, biologics, physical therapy exercises, gut microbiota, and analytical methods. DISCUSSION: This first bibliometric analysis of AS-related EBM research showed a 20-year upward trend in AS meta-analyses, consistent with prior studies. CiteSpace revealed that China (top since 2014) and the USA led in publications (53 countries) but had limited collaboration. Pan Faming (23 articles) was the most active author, and Annals of the Rheumatic Diseases published the most articles. Keyword analysis identified five themes (e.g., AS complications, biologics) and research frontiers: pre-2012 genome-AS links, post-2012 multi-center RCTs, and the recent focus on AS patients' HRQoL. Limitations included database and English-language bias; future meta-analyses should adopt standardized outcomes. CONCLUSION: In recent years, there has been a remarkable surge in the number of meta-analyses on AS. This significant increase underscores the importance of this research area. Studies in this field have mainly focused on several key aspects: risk factors, network meta-analysis, and quality- of-life studies. These findings are highly valuable for understanding advancements in ASrelated research and can also encourage researchers and clinicians to focus on both effective medical treatments and the well-being of AS patients.

Spondylitis, Ankylosing

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P&#x202f;<&#x202f;.0001; equivalent to -4.0&#x202f;mmol/mol). Heterogeneity was moderate-to-substantial (I&#xb2; = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P&#x202f;=&#x202f;.31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans

Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16&#x2009;G) or 18-gauge (18&#x2009;G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16&#x2009;G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18&#x2009;G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16&#x2009;G and 17.5 with 18&#x2009;G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist.

Humans

Interleukin-23 Receptor and Interleukin-17 Receptor A: Splice Variants, Isoforms and Their Relationship With Periodontitis-A Systematic Review and Bioinformatic Analysis.

This systematic review aimed to: (1) identify the splicing variants of IL23R and IL17RA reported in the literature; (2) perform a multiple alignment analysis to describe the isoforms of IL-23R and IL-17RA; and (3) compare the expression levels of IL-23R, IL-17RA, and their soluble isoforms (sIL-23R and sIL-17RA) in patients with periodontitis and periodontally healthy individuals. The study protocol followed PRISMA guidelines and was registered in PROSPERO (CRD420251267367). Six databases (PubMed, ScienceDirect, Scopus, Web of Science, EBSCO, and Google Scholar) were searched without restrictions on year or language. The descriptors used were: 'Interleukin-23 Receptor,' 'IL-23R,' 'Interleukin-17 Receptor A' 'IL-17RA,' 'Alternative Splicing,' 'Splice Variants,' 'Isoforms,' and 'Periodontitis.' The bioinformatics analysis was performed using CLUSTALW (V.1.83), InterPro and DeepTMHMM. Risk of bias was assessed with the QUIN and JBI tools for cross-sectional studies. Of 104 articles, four in&#xa0;vitro studies and eight cross-sectional studies were included. Qualitative analysis revealed that to date there are 32 splicing variants of the IL23R gene, while only one splicing variant has been reported for IL17RA. CLUSTALW, InterPro and DeepTMHMM analysis showed that these splicing variants result in 23 isoforms which can be soluble forms, complete intracellular peptides, truncated extracellular or intracellular peptides, or complete structures with truncated extracellular and/or intracellular domains. All studies had a low risk of bias. IL-23R and IL-17RA exhibit structural diversity resulting from alternative splicing, with IL-23R demonstrating significantly greater isoform complexity. However, the biological significance of these isoforms in periodontitis remains unclear and requires further investigation.

Humans

Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.

BACKGROUND: Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects. OBJECTIVE: This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and &#x2265;3 grades for analysis. PATIENTS/MATERIALS AND METHODS: Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed. RESULTS: Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade &#x2265;3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001. CONCLUSION: Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.

Humans

Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.

OBJECTIVE: Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS: Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS: As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION: Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Bayes Theorem

Quantitative Outcomes for Shared Assessment and Management in Forensic Mental Health: A Meta-Analysis and Systematic Review.

Despite leading models of mental health care encouraging user involvement, users in forensic mental health (FMH) report poor involvement given the difficulty in reconciling shared approaches with risk-averse and legally mandated settings. While previous research has demonstrated qualitative benefits to shared approaches in FMH and has led to a proliferation of self-rated assessment tools, there remains to quantify agreement on self-rated tools and to clarify the impact of shared approaches on care. This meta-analysis examines (1) the correlation between clinician and user ratings, (2) the predictive validity of self-ratings for violence, and (3) the effects of shared risk management on violence and restriction in FMH. Five databases were searched from inception to April 2024, selecting for adult FMH inpatients, shared risk assessment, needs assessment or violence management as interventions, and quantitative outcomes (correlation, agreement, predictive validity, and effect on violence or restriction rates). Fifteen quantitative evaluations were retained. One of three planned meta-analyses could be conducted, with seven records providing paired clinician-user t-tests. Eleven more records provided clinical recommendations on operationalizing shared approaches. Random-effects meta-analysis showed a significant and large paired standard difference of .95 (95% CI&#x2009;=&#x2009;[.49,1.42]) across tools, with significant differences in DUNDRUM-3, DUNDRUM-4, and CANFOR sub-models. While acknowledging between-study heterogeneity, results substantiate quantitative differences where clinicians generally rate more needs and lesser progress than users across tools, showing that self-ratings can and should be used to broach collaborative discussions on needs and progress during FMH treatment. There remains an evidence gap for quantitative benefits in care outcomes and a need to standardize agreement measures for future comparisons and clinical sub-group analyses.

Humans

High-Flow Nasal Oxygen Versus Conventional Oxygen Therapy and Non-Invasive Ventilation for Acute Respiratory Failure in the Emergency Department: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis compares the use of high-flow nasal oxygen (HFNO) with conventional oxygen therapy (COT) and non-invasive ventilation (NIV) in the management of acute respiratory failure (ARF) in the emergency department (ED). A comprehensive search of relevant sources was undertaken. Randomised controlled trials (RCTs) assessing adult patients (&#x2265;&#x2009;18&#x2009;years) treated in the ED for ARF and comparing HFNO to COT/NIV were included. The primary outcome was the need for endotracheal intubation and mechanical ventilation (IMV). Secondary outcomes included physiological and biochemical parameters, ICU admission, hospital length of stay, dyspnoea scores and mortality. A total of 17 RCTs (1955 patients) were included. There was a significant reduction in IMV favouring the HFNO group compared to COT and NIV (RR 0.64, 95% CI 0.47-0.88). HFNO showed significant improvements in RR, SpO2, PaO2 and Modified Borg Dyspnoea Scale. Subgroup analysis showed reduced rates of IMV with HFNO compared to COT (RR 0.61, 95% CI 0.41-0.91), but not compared to NIV (RR 0.69, 95% CI 0.42-1.14). HFNO additionally showed a reduction of IMV compared to NIV and COT in undifferentiated patients (RR 0.61, 95% CI 0.41-0.93), but not in exacerbations of COPD or acute heart failure. Ten of the 17 studies had at least some concern for risk of bias, with several analyses having notable heterogeneity. HFNO showed a significant reduction in rates of IMV, improvement in peripheral oxygen saturations, PaO2, respiratory rate and patient dyspnoea scores compared to COT and NIV.

Humans