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Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p&#x2009;<&#x2009;0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2&#x2009;=&#x2009;50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans

Clinical performance of two lithium disilicate CAD/CAM materials in posterior Class II inlay restorations: A 48-month randomised split-mouth clinical trial.

OBJECTIVES: To compare the clinical performance of Amber Mill (AM) and IPS e.max CAD (EM) lithium disilicate computer-aided design/computer-aided manufacturing (CAD/CAM) materials in posterior Class II inlay restorations and characterise their baseline properties. METHODS: Thirty-four adults received paired AM and EM posterior Class II inlays (68 restorations) in a triple-blind randomised split-mouth trial followed for 48 months. Restorations were evaluated at baseline and annually using revised World Dental Federation (FDI) criteria, with fracture and retention as the primary endpoint. Baseline characterisation included flexural strength, shear bond strength, translucency parameter, and scanning electron microscopy. McNemar, Wilcoxon signed-rank, Friedman, one-way analysis of variance, Tukey post hoc, and inter-rater agreement analyses were used. RESULTS: At 48 months, 18 paired participants were available for primary analysis. Failures occurred in 2 of 18 AM restorations and in 3 of 18 EM restorations, corresponding to success rates of 88.9% and 83.3%, respectively, with no significant between-material difference (McNemar p = 1.000). No catastrophic bulk ceramic fracture was observed. Secondary FDI scores remained mostly within the clinically acceptable range; marginal staining deteriorated over time in both groups (p < .001) without significant between-material differences. Baseline material testing showed significant material- and translucency-dependent differences in flexural strength, shear bond strength, and translucency. CONCLUSIONS: Within the limitations of the 48-month follow-up and the tested Class II inlay indication, AM showed clinical performance comparable to EM. Observed clinical complications were related to retention or marginal/interface behaviour. CLINICAL SIGNIFICANCE: For posterior Class II lithium disilicate CAD/CAM inlays, medium-term complications were mainly retention/interface-related, suggesting adhesive-interface durability may be as important as baseline ceramic strength.

Humans

Effects of carbohydrate mouth rinse on psychophysiological responses, kinematic variables and technical actions during small-sided soccer games.

BACKGROUND: This study investigated the effects of carbohydrate mouth rinsing (CHOMR) on various psychophysiological, kinematic, and technical actions during 4-a-side small-sided soccer games (SSGs). METHODS: In a randomized, crossover, double-blind design, 16 young male soccer players (age: 15&#x2009;&#xb1;&#x2009;1 years; height: 172.6&#x2009;&#xb1;&#x2009;7.0&#x2009;cm; body mass: 57.8&#x2009;&#xb1;&#x2009;7.9 kg) participated in two 4-a-side SSGs separated by one week following either CHOMR or placebo (PLA). During each SSGs, heart rate (HRmean, %HR, and HRmax), rating of perceived exertion (RPE), enjoyment, visual analogue scale (VAS) to perceived mental fatigue, mood states, total distance (TD), high-speed running distance (HSRD), average metabolic power (AMP), high metabolic load distance (HMLD), sprint distance (SD), acceleration (ACC), deceleration (DEC), and technical actions (e.g. passing, tackling, shooting, and interceptions) were assessed. RESULTS: Compared with PLA, CHOMR resulted in significantly higher RPE (p&#x2009;=&#x2009;0.025, g&#x2009;=&#x2009;0.86) and significantly lower VAS scores (p&#x2009;=&#x2009;0.010, g&#x2009;=&#x2009;-0.71). In addition, the CHOMR condition showed significantly higher values for interceptions, successful tackles, unsuccessful tackles, unsuccessful shots, and goals (p&#x2009;<&#x2009;0.05, g&#x2009;=&#x2009;0.96-2.02), whereas block values were significantly higher in the PLA condition. There were no statistically significant differences in HRmean, %HR, HRmax, enjoyment, TD, HSRD, AMP, HMLD, SD, ACC, DEC, successful passes, unsuccessful passes, successful shots, or mood states between the conditions (p&#x2009;>&#x2009;0.05). CONCLUSION: The current study findings suggest that CHOMR may enhance selected technical actions and lower VAS scores during 4-a-side SSGs, although it was also associated with higher RPE and did not alter the kinematic responses. In conclusion, CHOMR was associated with higher RPE, lower mental fatigue, and selective improvements in technical actions, with no significant effects on kinematic variables or HR.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Efficacy and safety of rib-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation at two different targets for primary palmar hyperhidrosis: a randomized controlled trial.

OBJECTIVES: To compare the efficacy and safety of computed tomography-guided percutaneous thoracic sympathetic radiofrequency thermocoagulation (RFT) targeting the upper versus lateral margin of the fourth rib head for severe primary palmar hyperhidrosis (PPH). METHODS: Patients with severe PPH were randomly divided into Group U (upper margin target) and Group L (lateral margin target). Outcome measures included 1-year recurrence rate, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI), palm skin temperature, finger perfusion index (PI), compensatory hyperhidrosis and patient satisfaction. RESULTS: Both groups (n&#x2009;=&#x2009;55 each, 110 sides) successfully underwent RFT. No preprocedural PI differences were found (p&#x2009;>&#x2009;0.05). Immediately post-RFT, PI in Group L was significantly higher than in Group U (left p&#x2009;=&#x2009;0.025, right p&#x2009;=&#x2009;0.013). No significant differences in HDSS grades were observed between groups before and at 1&#x2009;day, 2&#x2009;weeks, 1&#x2009;month and 3&#x2009;months post-procedure. However, at 6 and 12&#x2009;months, Group L showed significantly lower HDSS grades (left p&#x2009;=&#x2009;0.033 and 0.016; right p&#x2009;=&#x2009;0.039 and 0.025) and lower DLQI scores (p&#x2009;=&#x2009;0.037 and 0.024) than Group U. Patient satisfaction did not differ within 6&#x2009;months, but Group L had significantly higher satisfaction at 12&#x2009;months (p&#x2009;=&#x2009;0.036). CONCLUSIONS: Targeting the lateral margin of the fourth rib head for RFT achieved greater efficacy, better quality of life and higher patient satisfaction compared to the upper margin target.

Humans

How AI-supported intelligent systems support infection prevention and control training in healthcare: A systematic review of educational functions and outcomes.

AIMS: Artificial intelligence (AI)-supported intelligent systems have been increasingly incorporated into infection prevention and control (IPC) education and training, primarily to support the monitoring of observable behaviors and the provision of feedback. However, existing evidence has focused largely on short-term compliance outcomes, with limited synthesis of the educational role of AI-supported intelligent systems in supporting sustained IPC competence. This systematic review examined how AI-supported intelligent systems have been designed and used to support IPC education and training, with a focus on system characteristics, educational functions, and reported outcomes. DESIGN: A systematic literature search was conducted across the PubMed/MEDLINE, Embase, Cochrane, and CINAHL databases. DATA SOURCES: A total of 18 studies met the inclusion criteria. Findings were qualitatively synthesized according to system design characteristics, educational functions, and outcome domains. REVIEW METHODS: Methodological quality was appraised using the Mixed Methods Appraisal Tool. RESULTS: Most AI-supported intelligent systems focused on hand hygiene and relied on fully automated monitoring systems to capture behaviors and provide performance feedback. Educational functions were predominantly limited to performance assessment, automated feedback, and reminders. Outcomes were mainly measured using compliance or performance metrics, whereas sustained behavioral change and decision quality were rarely assessed. CONCLUSIONS: AI-supported intelligent systems have been used primarily to reinforce short-term IPC performance and compliance. However, their current applications for supporting sustained competence over time remain limited. The findings of this review suggest that AI-supported intelligent systems may serve as maintenance-oriented educational support by extending learning beyond initial instruction through repeated practice and feedback. Future research should prioritize outcome measures that capture the durability of performance and decision-making processes to better align AI-supported intelligent systems used in IPC education and training with the educational demands of clinical practice.

Humans

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p&#x2009;<&#x2009;0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p&#x2009;=&#x2009;0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% &#xb1; 20.7% vs. -20.09% &#xb1; 22.2%; p&#x2009;<&#x2009;0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p&#x2009;<&#x2009;0.001). At 24&#x2009;h postoperatively, QoR-15 scores were higher in the superior trunk block group (p&#x2009;=&#x2009;0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans

The prevalence of isthmic and degenerative lumbar spondylolisthesis: an analysis of 1376 patients.

INTRODUCTION: Typically, spondylolisthesis is an asymptomatic spinal condition that is often captured accidently in radiographic studies. The limited studies reviewing incidence primarily used lateral radiographs, which lack the granularity of advanced imaging. In response, computed tomography (CT) has been recommended to enhance the accuracy of spondylolisthesis diagnosis (degenerative versus isthmic). In the present study, we sought to determine the prevalence of isthmic and degenerative spondylolisthesis using CT imaging. METHODS: We conducted a retrospective study of 1,680 patients who underwent abdominal/pelvic CT scans at a single level-1 trauma center from January 1, 2017, to January 31, 2017. RESULTS: A total of 1,680 CT scans were screened, of which 1,376 patient scans met the inclusion criteria of having undergone complete imaging (axial and sagittal images). The average age of the study population was 57.1 (standard deviation, 18.7) years; 51.1% were female, and 83.2% were Caucasian. The prevalence of isthmic spondylolisthesis was 5.4% (n&#xa0;=&#xa0;71): 3.6% of cases were at the L5-S1 level, 2.1% were at the L4-L5 level, and 0.6% were at the L3-L4 level. The female-to-male ratio was 0.73:1. The prevalence of degenerative spondylolisthesis was higher at 21.5% (n&#xa0;=&#xa0;285), and the level most commonly affected was L4-L5 (11.8%), followed by L5-S1 (9.7%) and L3-L4 (4.6%). The female-to-male ratio was 1.3:1. There was a higher prevalence of degenerative spondylolisthesis in women at L4-L5 (51.2% vs. 35.6%; P&#xa0;<&#xa0;0.001). CONCLUSION: We found that degenerative spondylolisthesis was more prevalent, occurring primarily in older women, between the L4-L5 vertebrae. On the other hand, isthmic spondylolisthesis more commonly occurred within male patients between the L5-S1 vertebrae. Our study is one of the first to recognize a high rate of degenerative spondylolisthesis within the L5-S1 region, highlighting the utility of CT scan to visualize spinal translation. LEVEL OF EVIDENCE: IV.

Humans

The identification of growth-promoting lncRNAs in oral cavity squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma (OCSCC) is an aggressive tumor that develops within the mouth of patients. Tumor-suppressor gene loss and genomic arrangements fuel tumorigenesis and transcriptional reprogramming. Understanding how these alterations contribute to OCSCC growth and cell survival may identify new therapeutic vulnerabilities or biomarkers. We profiled the role of long non-coding RNAs (lncRNAs) in the growth of three OCSCC cell lines using a CRISPRi-screen and identified 19 lncRNAs that contribute to OCSCC proliferation. By comparing these lncRNAs to other screens, we find that these lncRNAs are uniquely required in OCSCC and not other malignancies. We show that these lncRNAs are abundantly expressed in OCSCC cells and tumors. Independent testing of candidate lncRNAs confirms their role in supporting OCSCC growth. Our results show that a novel subset of lncRNAs are required for the growth of OCSCC cancer cells and that these lncRNAs are cell lineage specific.

CRISPRi

Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.

The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.

Humans

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H&#x2082;O&#x2082;-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans

Clinical performance evaluation of single-shade versus multi-shade composite resins in non-carious cervical lesions: a 36-month randomized clinical trial.

BACKGROUND: Composite resins are widely used as the material of choice for definitive restorations due to their ability to integrate functional and aesthetic aspects in dental rehabilitation. Recently, one-shade composite resins have been introduced to simplify the clinical workflow. OBJECTIVES: This study aimed to compare the clinical performance of a "chameleon effect" composite resin with that of a multi-shade composite resin in non-carious cervical lesions after 36 months of follow-up. METHODS: This study was a randomized, controlled, double-blind clinical trial with an equivalence design using a split-mouth approach. The sample consisted of 60 patients presenting at least two non-carious cervical lesions, totaling 120 restorations. Restorations were performed using two materials from the same commercial brand: Vittra Unique (one-shade group) and Vittra APS (multi-shade group). The clinical performance of the restorations was longitudinally evaluated according to the FDI criteria. Survival analysis was performed using Kaplan-Meier curves and the log-rank test, while other clinical parameters were compared using the chi-square test (&#x3b1; = 0.05). RESULTS: At baseline, no statistically significant differences were observed between the groups regarding the evaluated biological, functional, and aesthetic parameters (p > 0.05). Both materials demonstrated clinically acceptable performance according to the FDI criteria, with no significant differences between them. CONCLUSIONS: After 36 months, no significant differences were observed between the one-shade and the multi-shade composite resins in the restoration of non-carious cervical lesions. CLINICAL SIGNIFICANCE: This 36-month randomized clinical trial demonstrates that single-shade composite resins achieve structural durability and aesthetic integration equivalent to traditional multi-shade layering when restoring non-carious cervical lesions. This evidence validates a simplified, single-shade restorative workflow, significantly reducing chairside time and operator-dependent variables without compromising the clinical longevity.

Humans

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products

A single session of high-definition transcranial direct current stimulation does not modulate effects of knee two-point discrimination training or sensorimotor function in healthy adults: Double-blind randomised controlled trial.

BACKGROUND: Benefits of sensory-training interventions on sensorimotor outcomes are inconsistent, and it is unclear whether transcranial direct current stimulation (tDCS) can enhance proprioception, which is fundamental to neuromuscular control. Existing evidence is dominated by upper-limb studies, so transferability to the knee is unclear. This study investigated whether a single session of anodal high-definition (HD)-tDCS, alone or combined with brief two-point discrimination (TPD) training, enhances knee sensorimotor function and performance in healthy adults. METHODS: In a double-blind randomised-controlled trial, 57 healthy participants received (1) 20-min, 1&#xa0;mA anodal HD-tDCS over the knee primary somatosensory (S1) map or sham stimulation, and (2) 15-min knee TPD training or no training. Knee somatosensory, sensorimotor, and functional performance measures were assessed pre- and immediately post-intervention. Three-way mixed-design ANOVAs, equivalence testing (smallest effect size of interest &#x3b7;2&#xa0;=&#xa0;0.02), Bayes factors, and linear mixed-effects models quantified effects. RESULTS: HD-tDCS, TPD training, and their sequential combination had no effect on any outcome measure (p&#xa0;&#x2265;&#xa0;0.05; &#x3b7;2&#xa0;&#x2264;&#xa0;0.015). Confidence intervals spanned equivalence bounds, and equivalence testing results were non-significant (p&#xa0;&#x2265;&#xa0;0.05). Bayes factors (<0.33) showed moderate evidence for the null (no effect). Mixed-effects modelling attributed &#x2264;8% of total variance to intervention fixed effects, with the remainder captured by participant-level random effects. CONCLUSION: A single 20-minute session of 1&#xa0;mA HD-tDCS, with or without brief TPD training, does not acutely modify knee somatosensory, sensorimotor, or functional performance in healthy adults. Existing evidence at the hand may not translate to the lower limb. Future work should investigate higher-dose, multi-session, task-concurrent, or network-targeted strategies in clinical populations.

Humans

Safety and efficacy of Meridian sinew tuina (MST) for post-surgical upper limb lymphedema: a systematic review and meta-analysis.

BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z&#x2009;=&#x2009;20.81; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (&#x2265; 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z&#x2009;=&#x2009;10.62; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N&#x2009;=&#x2009;924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD&#x2009;=&#x2009;-1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD&#x2009;=&#x2009;-2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.

Humans

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

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Distal versus proximal radial access for diagnostic cerebral angiography: comparative outcomes and learning curve analysis.

BACKGROUND AND PURPOSE: Distal transradial access (dTRA) is an alternative to proximal transradial access (pTRA) for neuroangiography, but comparative real-world data and evidence on its early learning curve remain limited. We compared procedural performance and access-site complications between dTRA and pTRA and evaluated the early learning curve of dTRA. METHODS: We retrospectively analyzed 470 diagnostic cerebral angiography procedures, representing 421 unique patients, performed via radial access at a single center between January 2025 and February 2026, including 237 dTRA and 233 pTRA procedures. Baseline characteristics, including age, sex, body mass index (BMI) category, aortic arch type, and antiplatelet/anticoagulant use, procedural performance, and clinically assessed access-site events were compared between groups. Radial artery occlusion (RAO) was assessed by postoperative bedside pulse examination and confirmed with Doppler ultrasound when clinical findings were uncertain. Multivariable logistic regression was used to evaluate predictors of RAO, persistent bleeding or repeated compression, hand edema, and a composite access-site event endpoint. Because repeated procedures occurred in a subset of patients and event counts were limited, first-procedure sensitivity analysis and analyses of infrequent outcomes were interpreted cautiously. The dTRA learning process was assessed in the first 100 dTRA cases performed by a single operator using multivariable regression, cumulative sum (CUSUM) analysis, segmented trend analysis, and phase-based comparisons. RESULTS: Baseline characteristics were comparable between groups, including age, male sex, BMI category, aortic arch type, and antiplatelet/anticoagulant use. Compared with pTRA, dTRA was associated with more puncture attempts (3.0 [2.0-4.0] vs 2.0 [1.0-3.0], P&#xa0;<&#xa0;0.001), longer puncture time (2.0 [1.0-5.0] vs 2.0 [1.0-3.0] min, P&#xa0;=&#xa0;0.003), lower first-pass success (19.4% vs 35.2%, P&#xa0;<&#xa0;0.001), and a higher crossover rate (11.4% vs 6.0%, P&#xa0;=&#xa0;0.037). However, dTRA was associated with a lower clinically assessed RAO rate (2.5% vs 7.7%, P&#xa0;=&#xa0;0.011). On multivariable analysis, pTRA was independently associated with higher odds of RAO (OR 3.27, 95% CI 1.26-8.49, P&#xa0;=&#xa0;0.015) and the composite access-site event endpoint (OR 3.12, 95% CI 1.55-6.28, P&#xa0;=&#xa0;0.001). Similar findings were observed in a sensitivity analysis restricted to the first procedure per patient. In the first 100 dTRA cases, cumulative dTRA experience was independently associated with shorter total procedure time (beta&#xa0;=&#xa0;-0.074&#xa0;min/case, P&#xa0;=&#xa0;0.009), while CUSUM and moving-average analyses suggested that the major learning effect occurred within approximately the first 10-15 cases. CONCLUSIONS: In this retrospective single-operator cohort, dTRA was associated with lower clinically assessed RAO than pTRA despite greater access difficulty. The early learning effect was mainly reflected in shorter total procedure time. These findings support the feasibility of dTRA but should be interpreted cautiously given the study's observational design and limited anatomical data.

Humans

Genetic overlap between estimated glomerular filtration rate and cardiovascular disease identifies potential targets for cardiorenal syndrome.

Heart and kidney diseases frequently coexist, but the genetic basis of this relationship remains unclear. We analyzed genetic data from large-scale studies to investigate how kidney function (estimated glomerular filtration rate, eGFR) and six common cardiovascular diseases share genetic risk factors. Using MiXeR method, and conjunctional false discovery rate (conjFDR) to identify overlapping genetic regions, we found 478 shared genomic loci between eGFR and cardiovascular diseases. These shared genes are involved in tissue development and structure. We also identified 29 genes that could be targeted by existing medications approved by the US Food and Drug Administration, such as PRKAG2, PDE1A, and IGF1R. Among these, genetically predicted higher level of IGF1R expression is associated with a higher eGFR, which reflects good kidney function and is protective against cardiorenal diseases, such as atrial fibrillation, and myocardial infarction. These findings reveal genetic overlap between kidney function and cardiovascular diseases, highlighting potential targets for understanding and treating cardiorenal syndrome.

Humans