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Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45 ± 3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+ P+ (APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans

Effect of Narrative-Based Palliative Care on Psychological Stress, Quality of Life, and End-of-Life Acceptance in Elderly Terminal Cancer Patients and Their Families.

ObjectiveThis study aimed to preliminarily evaluate the impacts of narrative-based palliative care on psychological stress, end-of-life acceptance, and quality of life in elderly terminally ill cancer patients and their family caregivers.MethodsThis single-center, small-sample randomized controlled study enrolled 50 elderly terminal cancer patients. Patients were randomly assigned to either the observation group or the control group (n = 25 each). The observation group received narrative-based palliative care, while the control group received routine standard care. Family psychological stress was assessed using the Relative Stress Scale (RSS), and patients' perceived stress was evaluated with the Perceived Stress Scale-10 (PSS-10). Caregiver satisfaction was measured using a hospital-developed questionnaire. Patients' quality of life was evaluated using the SF-36, Chinese Version of the Death Attitude Profile (DAP-C), and Pittsburgh Sleep Quality Index (PSQI), respectively.ResultsBaseline characteristics did not differ significantly between the two groups (P > .05). Post-intervention, the observation group demonstrated significantly lower psychological stress among family members and higher caregiver satisfaction (P < .05). Patients in the observation group reported better quality of life, improved sleep, and greater acceptance of death than those in the control group (P < .05).ConclusionAs a small-sample, single-center study, these findings offer preliminary evidence that narrative-based palliative care may reduce psychological stress in elderly terminal cancer patients and caregivers while enhancing patients' quality of life, sleep quality, and acceptance of death. However, the limited sample size, single-site design, and narrow inclusion criteria restrict generalizability. Larger multicenter trials are needed to confirm these results.

Humans

Meta-analysis of growth and inactivation kinetics of Legionella.

Quantitative risk assessments intended to inform evidence-based water management plans and public health targets for Legionella in engineered water systems are constrained by fragmented and heterogeneous growth and inactivation kinetics. We conducted a meta-analysis of 25 growth and 39 thermal- and chemical-inactivation studies, fitting microbial persistence models to harmonize parameters. Nonlinear models outperformed first-order formulations, indicating that lag phases and resistant or protected subpopulations are central to Legionella persistence. Random forest analysis identified environmental and methodological drivers of variability based on 226 growth rates and reduction times for thermal (209) and chemical (135) inactivation. Growth was primarily governed by temperature, nutrient availability, and compatible Legionella-host pairings; thermal inactivation by quantification method, temperature, and turbidity; and chemical inactivation by inoculum size, disinfectant type, concentration, and host-associations. Accordingly, temperature-dependent growth parameters and exposure metrics for heat, free-chlorine, and monochloramine, expressed as TT (Temperature&#xd7;time) and CT (Concentration&#xd7;time), were derived as condition-specific inputs for predictive models. Growth optima around 37-40 &#xb0;C, together with lag-time estimates, indicate that hot-water temperature setbacks and energy-saving practices may favor Legionella proliferation under repeated or prolonged lukewarm exposure. Culture- and viability-based TT differences highlight the need to consider viable&#x2011;but-non-culturable persistence in monitoring programs. CT comparisons suggest monochloramine may be advantageous because of its lower apparent sensitivity to host-associated protection. Although limited by restricted experimental conditions, the findings show that predictive models should account for microbial ecology, water matrix effects, and quantification endpoints. Future kinetic studies should prioritize realistic multi-host systems, strain pre-adaptation, complementary viability measurements, and standardized protocols and reporting to ensure reproducibility and enable robust system-level predictive modeling.

Legionella

Genome-wide insights into the evolutionary and demographic history of the red alga Mazzaella laminarioides: Evidence for speciation with ancient migration along the southeast Pacific coast.

The mechanisms driving lineage divergence in red algae remain unexplored, despite the group's remarkable diversity and ancient evolutionary history. The red alga Mazzaella laminarioides, a Chilean intertidal species complex composed of three parapatric cryptic lineages (North, Center, South), offers a valuable system to evaluate these processes, as its life history combines severe dispersal limitation with a haploid-diploid cycle that may influence the emergence of reproductive barriers. We reconstructed its evolutionary history using whole-genome sequencing and nuclear genome assembly of representative individuals from each lineage. Phylogenomic analyses based on 1,507 single-copy orthologs recovered three deeply divergent lineages with limited nuclear discordance consistent with incomplete lineage sorting. For both splits, demographic modelling was most consistent with an Ancient Migration scenario, although support over strict isolation was moderate, suggesting that divergence may have begun with low asymmetric ancestral gene flow followed by subsequent loss of connectivity, demographic bottlenecks, and later population expansion. Coding sequence analyses revealed lineage-specific dN/dS heterogeneity; only one South-lineage locus passed FDR correction (metaxin-1, mitochondrial protein import), with two further South-lineage candidates in chlorophyll and heme biosynthesis falling below the FDR threshold. Together, these signals suggest that divergent selective pressures on energy acquisition may have contributed to divergence at the southern end of the distribution. These results add to the small but growing body of whole-genome data for red algae and, alongside recent macroalgal studies, suggest that ancestral connectivity could be a recurrent feature of lineage divergence even in marine organisms with extremely restricted dispersal.

Rhodophyta

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66&#xa0;years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals

The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games

Virtual surgical planning-assisted versus free-hand head and neck reconstruction: Systematic review, meta-analysis, and a novel classification.

Virtual surgical planning (VSP)-assisted reconstruction is increasingly used as an alternative to conventional free-hand (FH) techniques in mandibular and maxillary free-flap reconstruction. This systematic review and meta-analysis compared clinical outcomes and proposed a Reconstruction Complexity-Completeness classification. PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and reference lists were searched from inception to 20 June 2026. Comparative studies were eligible. Risk of bias was assessed using RoB 2 or the Newcastle-Ottawa Scale. Random-effects meta-analyses used restricted maximum likelihood estimation and Hartung-Knapp adjustment. Forty-two studies included 2763 patients (1204 VSP; 1559 FH). VSP significantly reduced operative time (33 studies; MD -64.75&#x202f;min, 95% CI -83.51 to -46.00), ischemia time (15 studies; MD -37.40&#x202f;min, 95% CI -48.97 to -25.82), and hospital stay (16 studies; MD -1.75 days, 95% CI -3.43 to -0.08). VSP was associated with significantly lower odds of bony non-union (OR 0.31, 95% CI 0.16-0.59) and malocclusion (OR 0.14, 95% CI 0.03-0.64), whereas flap loss, surgical site infection, and plate exposure did not differ significantly. VSP-assisted reconstruction was associated with improved operative efficiency, shorter hospitalization, and lower odds of bony non-union and malocclusion, while no statistically significant differences were detected in flap loss, surgical site infection, or plate exposure. The proposed classification may support complexity-adjusted reporting and comparison.

Humans

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41&#xa0;&#xb1;&#xa0;0.24 vs. 2.35&#xa0;&#xb1;&#xa0;0.06, P&#xa0;<&#xa0;0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4&#x207a; regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogot&#xe1;, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (&#x223c;2.4-fold decrease in median expression; p&#x202f;=&#x202f;0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p&#x202f;=&#x202f;0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p&#x202f;=&#x202f;0.035) and Amerindian ancestry (p&#x202f;=&#x202f;0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent

The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with &#x2265;&#xa0;99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans

Molecular diagnostic yield and barriers in inherited retinal diseases: a retrospective cohort study.

OBJECTIVE: To evaluate the diagnostic yield of panel-based genetic testing for inherited retinal diseases (IRDs) and identify barriers to molecular resolution. DESIGN: Retrospective cohort. PARTICIPANTS: A total of 404 patients with clinically confirmed IRDs who were evaluated at the Adult Inherited Retinal Dystrophy Service, Ontario, Canada (October 2021-September 2024). METHODS: Patients underwent targeted massive parallel sequencing panel testing. Diagnostic yield was calculated, and unresolved cases were reviewed. Associations between yield, phenotype, ethnicity, and sex were assessed using &#x3c7;&#xb2; analysis. RESULTS: Of 685 referrals, 570 had confirmed IRDs. After we excluded 140 pending results and 26 patients who declined testing, 404 patients were analyzed. At referral, 94 patients (23.2%) had a previous molecular diagnosis, and 138 (34.0%) were diagnosed through clinic-initiated testing, giving an overall yield of 57.4%. Yield varied significantly by phenotype (&#x3c7;&#xb2;, P&#x202f;=&#x202f;1.4&#x202f;&#xd7;&#x202f;10&#x207b;&#x2076;), from 94.4% in vitelliform macular dystrophies to 25.0% in vitreoretinopathies, with no sex association (P&#x202f;=&#x202f;1.0). Disease-causing variants were identified in 83 IRD-associated genes, most frequently ABCA4, USH2A, and BEST1. Of 172 unresolved cases, 62 (36.0%) had negative panels, and 110 (63.9%) were inconclusive, including 30 with unphased pathogenic variants in recessive genes and 10 with high-suspicion variants of uncertain significance. Key barriers included limited family availability for phasing, restricted access to functional assays, and lack of public coverage for whole-exome or whole-genome sequencing. CONCLUSIONS: Massive parallel sequencing-based panel testing achieved a 57% diagnostic yield in this IRD population. Success was strongly phenotype-dependent with substantial heterogeneity. Whole-exome sequencing, whole-genome sequencing, family segregation, and functional genomics could improve diagnostic outcomes and management.

Humans

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

Therapeutic approaches for the treatment of bovine metritis: a systematic review of clinical, reproductive and productive outcomes.

Bovine metritis is a complex multifactorial disease associated with substantial clinical and economic impact due to reduced milk production, subfertility, and increased culling rates. Considerable uncertainty remains regarding the comparative efficacy of the many therapeutic strategies used to manage it. This systematic review aimed to summarize and critically evaluate the available evidence on therapeutic approaches for bovine metritis, with respect to clinical cure, reproductive performance, productive performance, and culling. A literature search conducted in PubMed, Web of Science and CABI Digital Library (2010-2025) identified 18 randomized controlled clinical trials eligible for inclusion. Risk of bias was assessed independently by two reviewers using the Cochrane RoB 2 tool. Given substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively by outcome, without meta-analytic pooling, and the certainty of evidence was assessed using GRADE for the comparisons supported by more than one study. Overall, systemic antimicrobial therapies consistently improved short-term clinical cure rates, although their effects on long-term reproductive and productive performance remained inconsistent. In selected cases, nonsteroidal anti-inflammatory drugs (NSAIDs) showed clinical outcomes comparable to antimicrobial treatments, allowing reductions in antimicrobial use ranging from 50% to 92%. Alternative approaches, such as intrauterine flavonoid, chitosan or dextrose-based therapies, produced inconsistent results that appeared to correlate with disease severity and treatment protocol. The evidence base is limited by substantial heterogeneity in disease definitions, postpartum timing of diagnosis, and cure criteria across studies, and by the near-universal absence of allocation concealment in the primary literature; these limitations restrict the certainty of most conclusions to low or moderate. Therefore, effective metritis control should move beyond symptom resolution and incorporate integrated and preventive strategies targeting inflammatory and metabolic dysregulation during the transition period.

Animals

The effect of nutrition education interventions on dialysis patients' outcomes: a systematic review and meta-analysis.

BACKGROUND: Non-adherence to dietary and fluid restrictions among dialysis patients is associated with adverse clinical outcomes. Quantifying the effectiveness of nutrition education interventions can inform practice and policy. METHODS: We searched MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, Web of Science, and Scopus up to 15 July 2025, supplemented by trial registries and Google Scholar, with an updated search through 8 April 2026. Eligible studies included randomized and non-randomized trials evaluating nutritional education interventions in adult dialysis populations. Risk of bias was assessed using RoB-2 and ROBINS-I, certainty graded using GRADE, and random-effects meta-analyses conducted alongside subgroup, sensitivity, and meta-regression analyses. Publication bias was assessed with Egger and Begg tests and trim-and-fill where applicable. RESULTS: Forty-four studies comprising 4,106 participants were included. Nutrition education significantly improved knowledge (SMD = 1.09; 95% CI: 0.67-1.51) and health-related quality of life (SMD = 1.43; 95% CI: 0.86-2.00; I&#xb2; = 0%), and reduced serum potassium (SMD = -0.52; 95% CI: -0.91 to -0.14; I&#xb2; = 92%) and serum phosphate (SMD = -0.35; 95% CI: -0.56 to -0.15; I&#xb2; = 81%). Results for albumin, creatinine, sodium, calcium, and BUN were inconsistent and non-significant. Most outcomes were rated low or very low certainty by GRADE, reflecting inconsistency, indirectness, and imprecision. Potential publication bias was identified for certain outcomes. CONCLUSIONS: Nutrition education consistently improves knowledge and quality of life and may modestly reduce serum phosphate and potassium in dialysis patients. High-quality registered trials with standardized outcomes and longer follow-up are needed to establish effectiveness and sustainability. PROSPERO REGISTRATION: CRD420251119567.

Humans

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals

Systematic review of the mutations in the active antigenic site &#xd8; of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site &#xd8; of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site &#xd8;, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p&#xa0;<&#xa0;0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans

Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis.

Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N&#x2009;=&#x2009;1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2&#x2009;=&#x2009;89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2&#x2009;=&#x2009;95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2&#x2009;=&#x2009;66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2&#x2009;=&#x2009;95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4&#x2009;>&#x2009;350 cells/&#x3bc;L vs. 71.1% in those with CD4&#x2009;&#x2264;&#x2009;200 cells/&#x3bc;L (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.

Humans