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Ten-Year Update of Nurse Practitioner Service Impact on Patient and Health Service Outcomes in Emergency Care Settings-A Systematic Review.

AIMS: To provide a 10-year update on the best available evidence evaluating the impact of nurse practitioner services on cost, waiting times, patient satisfaction, representation rates, and length of stay in emergency and urgent care settings. DESIGN: Systematic review. DATA SOURCES: The search was completed on January 28, 2025, in Embase (Elsevier), Medline (EBSCOhost), CINAHL (EBSCOhost), Cochrane Library (Wiley), Emcare (Ovid), Web of Science Core Collection (Clarivate) and Scopus (Elsevier). The data range (2014-2024) was used to limit the search. METHODS: The search was conducted with results imported into Covidence. In Covidence, two reviewers conducted screening, data extraction, and quality appraisal of articles, and findings were analysed using a narrative synthesis approach. Eligible studies examined nurse practitioner services in emergency or urgent care settings, reporting outcomes of cost, waiting times, patient satisfaction, representation rates, and length of stay. RESULTS: Title and abstract screening were performed on 2329 records. Of these, 236 full-text articles were reviewed, and 17 underwent critical appraisal and data extraction. Narrative analysis of outcome measures yielded mixed results, with both favourable and unfavourable findings reported regarding nurse practitioner services. CONCLUSIONS: Global evaluation of nurse practitioner services in emergency care remains inconsistent. Nevertheless, emerging evidence supports their positive impact, particularly in improving patient outcomes. To effectively inform policy, workforce planning and clinical integration, there is a need for professional benchmarks that provide clear frameworks for the evaluation of patient-centred outcomes and operational impacts in emergency departments. IMPLICATIONS: Evidence related to nurse practitioner services in emergency and urgent care clinics highlights the positive impact of nurse practitioner services on patient wait times and satisfaction; however, there is limited and variable evidence of impact on health care costs and outcomes. IMPACT: This paper recommends that evaluating emergency nurse practitioner services requires homogeneous research using consistent professional benchmarks and evaluation frameworks. REPORTING METHOD: This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. PATIENT OR PUBLIC CONTRIBUTION: This study did not include patient or public involvement in its design, conduct, or reporting. TRAIL REGISTRATION: PROSPERO 2025 CRD420250645148.

Humans

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30&#x2011;day all&#x2011;cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged&#xa0;&#x2265;&#xa0;60&#xa0;years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K&#x2011;Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P&#xa0;<&#xa0;0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR&#xa0;=&#xa0;9.752), smoking (OR&#xa0;=&#xa0;5.171), AIP (OR&#xa0;=&#xa0;6.691), TyG index (OR&#xa0;=&#xa0;4.393), HALP score (OR&#xa0;=&#xa0;2.831), and&#xa0;&#x2265;&#xa0;2 comorbidities (OR&#xa0;=&#xa0;3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC&#xa0;=&#xa0;0.884, accuracy&#xa0;=&#xa0;0.829, sensitivity&#xa0;=&#xa0;0.812, specificity&#xa0;=&#xa0;0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30&#x2011;day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans

Emerging Principles in Spatial Functional Genomics.

Spatial transcriptomic and proteomic atlases have enabled mapping of gene programs within intact tissues, but these measurements remain largely descriptive and do not define the mechanisms controlling tissue biology. Pooled CRISPR screening provides scalable causal interrogation of gene function but remains largely confined to dissociated systems that lack spatial context. In vivo spatial functional genomics (SFG) bridges these approaches by integrating genetic perturbations with in situ transcriptomic and proteomic readouts to measure gene function within intact tissue ecosystems. By preserving spatial organization, SFG enables interpretation of perturbations through effects on cell-cell interactions, diffusible signals, multicellular niches, and tissue architecture. Here, we outline key design axes of SFG: perturbation strategy, barcoding strategy, and phenotypic readout. We discuss computational challenges, including spatial autocorrelation, neighborhood dependence, and context-aware null modeling, and highlight how SFG reveals non-cell-autonomous, architecture-dependent mechanisms of gene function, advancing toward predictive models of tissue organization and gene function.

Genomics

Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resources limit routine monitoring of all patients, trauma care remains largely symptom-driven. The combination of long-term disability and limited capacity for routine follow-up highlights the need for risk-stratified follow-up care and reliable evidence on early prognostic factors. However, the existing literature is sparse and methodologically heterogeneous, limiting the clinical applicability of findings. We therefore conducted a systematic review and meta-analysis to identify early risk factors for poorer long-term mental health and HRQoL outcomes. A systematic search of seven electronic databases identified studies of adult patients with TBI, with outcomes assessed at least 6 months postdischarge. Two authors independently screened the studies, assessed the risk of bias, and extracted the data. We pooled effect estimates using a random-effects meta-analysis and calculated 95% prediction intervals. A narrative synthesis was applied when meta-analysis was not feasible. The review was registered with PROSPERO (CRD42024576912) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 8,104 articles screened, 64 studies met the inclusion criteria (n = 334,672). Most studies (58%) had a low risk of bias. Female sex, socioeconomic disadvantage, psychiatric history, assaultive-related injuries, and previous TBI were consistently associated with worse long-term outcomes. Across meta-analyses, assault-related injuries more than doubled the odds of post-traumatic stress disorder (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 2.01-3.66, I2 = 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, I2 = 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, I2 = 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, I2 = 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, I2 = 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, I2 = 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, I2 = 98%) were associated with higher odds of depression. Furthermore, higher pooled anxiety scores were observed in females and in individuals with a psychiatric history. The study identified several readily available factors present before or at discharge that are associated with poor long-term HRQoL and mental health outcomes. Leveraging these factors in follow-up protocols, prediction modeling, and clinical decision support systems may facilitate risk-stratified postdischarge care for TBI patients.

Humans

Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed-Loop/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study-Level Synthesis.

BACKGROUND: Hybrid closed-loop (HCL) systems achieve rapid, algorithm-driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question. METHODS: A systematic review and structured quantitative synthesis was performed using study-level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study-level proportions, and comparative studies were summarised using study-specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow-up duration, and comparator groups, no pooled or meta-analytic estimates were derived. RESULTS: Eight studies (n&#x2009;=&#x2009;1487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within &#x2264;&#x2009;12&#x2009;months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow-up reported lower rates of retinal worsening or incident DR, 6.7% at 24&#x2009;months and 6.1% over a mean follow-up of 4.9&#x2009;years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study-specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre-HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes. CONCLUSIONS: Study-defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well-designed prospective studies with protocol-specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.

Humans

Integrated transcriptomic and metabolomic analysis of fluoride tolerance-related pathways and differentially expressed genes in silkworm strain XSKD.

XueSong KD (XSKD) silkworm strain exhibits prominent fluoride tolerance, yet the underlying molecular mechanisms of fluoride tolerance remains unclear. In the present study, fourth-instar pre-molting XSKD silkworms were used as experimental materials for integrated transcriptomic and untargeted metabolomic analyses. In total, 572 differentially expressed genes and 90 differential metabolites were screened. GO enrichment and KEGG enrichment based on the hypergeometric distribution model revealed that 13-Hydroxy-9Z,11E-octadecadienoic acid (13-(S)-HODE) acts as the core differential metabolite, which is significantly enriched in the linoleic acid metabolism pathway. Within this pathway, LOC101737302 and CYP338A1 display opposite expression trends and show correlations with pathway metabolites. Based on multi-omics data, this study preliminarily characterizes the lipid metabolic response under fluoride stress, providing omics dataset support for further in-depth exploration of the molecular mechanism of fluoride tolerance in silkworms.

Animals

Comparative Efficacy of Different AI Systems for Polyp Detection by Size During Colonoscopy: Systematic Review and Network Meta-Analysis.

BACKGROUND: Colorectal cancer remains a leading cause of death despite being largely preventable through polypectomy. AI systems designed to enhance polyp detection during colonoscopy have shown promise, but the extent to which they improve detection of different-sized polyps remains unclear. OBJECTIVE: This study compared the size-stratified efficacy of AI-assisted colonoscopy vs standard colonoscopy using the Hartung-Knapp-Sidik-Jonkman (HKSJ) method, and generated exploratory rankings while acknowledging all cross-platform comparisons are indirect. METHODS: This systematic review and network meta-analysis (NMA) searched PubMed, Embase, Cochrane CENTRAL, and Web of Science from inception to July 25, 2026, supplemented by citation searching. We included randomized controlled trials (RCTs) comparing AI-assisted vs standard colonoscopy in adults (&#x2265;18 years of age), reporting mean polyp detection counts stratified by size (&#x2264;5 mm, 6-9 mm, and &#x2265;10 mm). Two reviewers screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0. We conducted frequentist NMA using the HKSJ method with restricted maximum likelihood estimation, calculated 95% prediction intervals (PIs), and assessed heterogeneity using I2 and &#x3c4;2. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. RESULTS: A total of 13 RCTs (4156 participants) compared 8 AI systems to standard colonoscopy, forming a network without direct AI comparisons. For diminutive polyps (&#x2264;5 mm), AI showed a modest advantage (standardized mean difference [SMD] 0.21, 95% CI 0.07 to 0.35, 95% PI -1.12 to 1.54), but substantial heterogeneity (I2=86.6%) and wide PI crossing the null indicated high uncertainty. EndoScreener showed the most consistent evidence (SMD 0.36, 95% CI 0.18-0.54). For small and large polyps, effects were minimal (SMD 0.02, 95% CI -0.02 to 0.06, 95% PI -0.03 to 0.07; SMD 0.01, 95% CI 0.00-0.02, 95% PI -0.01 to 0.03). GRADE certainty was very low for diminutive polyps and low for small and large polyps. Sensitivity analysis excluding Tianjin YuJin did not materially change findings. CONCLUSIONS: AI may modestly enhance diminutive polyp detection, but effects on small and large polyps are minimal, with no platform superiority. Given very low to low certainty, findings are hypothesis-generating. This exploratory NMA provides size-stratified comparisons that can inform future head-to-head trial design. Unlike prior reviews aggregating all polyp sizes, we show the overall AI benefit is driven by diminutive polyp detection, providing a framework for targeted deployment-prioritizing AI for diminutive polyp screening, with limited value for larger lesions. Head-to-head trials are urgently needed. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD420251266932; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251266932.

Colonoscopy

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-&#x3b2; (A&#x3b2;) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article

Financial Literacy Skills Instruction Among Autistic Individuals: A Systematic Review.

PURPOSE: Financial literacy skills are crucial for an independent life in modern societies. However, it does not appear that researchers have examined financial literacy skills among autistic individuals. This manuscript uses a systematic review to identify existing research which examines financial literacy skill instruction for autistic individuals. METHOD: We used a systematic review strategy to identify approximately 9500 articles. These articles proceeded through abstract and full-text screening for relevance. RESULTS: We identified two studies which directly taught financial literacy skills, and ten more which taught more basic money skills (such as calculating change). Neither of the two studies which taught financial literacy skills did so as an exclusive focus; both taught these skills alongside other objectives, as part of a larger intervention. CONCLUSIONS: Research on financial literacy skill instruction among autistic individuals is lacking, though there is a foundation of research examining money skills and related life skills to build upon. We recommend additional research on financial literacy skill instruction, ideally designed with the unique skills and needs of autistic individuals in mind, and with their input.

Humans

Metal-organic frameworks nanozyme-integrated portable microneedle patch for visual bacterial monitoring in meat.

Foodborne microbial contamination is a major global health concern, with conventional methods often being time-consuming and complex. Herein, we developed a novel portable biosensor by integrating microneedle patch technology and a metal-organic framework (Fe/Cu-NBDC MOF) nanozyme, enabling rapid, on-site, visual detection of bacteria in meat. The sensing system works by encapsulating aptamer-functionalized MOF nanozymes within a hydrogel patch, where their catalytic sites are initially blocked by the aptamer. In the presence of Staphylococcus aureus (S. aureus) as the target, the specific aptamer's binding to bacteria exposes numerous catalytic sites, further activating the chromogenic reaction of the tetramethylbenzidine&#x2011;hydrogen peroxide (TMB-H&#x2082;O&#x2082;) system, enabling visual detection of S. aureus. The biosensor demonstrates a detection limit of 82&#xa0;CFU/mL with excellent specificity to successfully apply to commercial mutton. By integrating sampling, enrichment, and visual detection into a single compact device, this platform offers a practical, efficient solution for rapid on-site screening of foodborne pathogens.

Biosensing Techniques

Algae-to-host horizontal gene transfer in Paramecium bursaria is associated with host adaptation during endosymbiosis.

Paramecium bursaria maintains a stable endosymbiosis with green algae, yet the evolutionary consequences of this association remain unclear. Here, we screened the host genome for algal-derived horizontally transferred genes (HTGs) using a lineage-aware workflow designed to detect horizontal gene transfer (HGT) between two defined lineages. We identified 16 candidate HTGs, including four putative newly transferred genes and 12 homologous transferred genes, most of which were functionally associated with redox homeostasis and metabolism. Five HTGs showed symbiosis-dependent expression. RNAi knockdown of GH32s and SATs reduced host proliferation, total cell area, and motility, while GH32s knockdown also reduced endosymbiont load. Duplication patterns suggest that most transfers may have occurred after the P. bursaria lineage diverged from the sampled Paramecium species but before its lineage-specific whole-genome duplication (WGD). The HTGs also showed host-associated shifts in GC content and gene length, while representative HTGs retained conserved domains and functional motifs. Together, our results support algae-to-host HGT in P. bursaria and suggest that some transferred genes may contribute to metabolic integration during endosymbiosis.

Gene Transfer, Horizontal

Importin-8 silencing reduces Ataxin-3 aggregation and alleviates Machado-Joseph disease/spinocerebellar ataxia type 3.

Machado-Joseph disease (MJD) is a polyglutamine neurodegenerative disorder characterized by the formation of neuronal intranuclear Ataxin-3 inclusions. The nucleocytoplasmic transport is known to be profoundly dysregulated from early stages of neurodegeneration, further aggravating its progressive nature. To understand the contribution of these proteins in MJD, we screened the effect of 34 transport proteins on Ataxin-3 aggregation. Importin-8 (Ipo8 gene) was selected for further neuropathology and behavior analysis to evaluate its modulatory effect in vitro and in vivo. Our results showed that Ipo8 mRNA expression is increased in MJD and that, upon Ipo8 downregulation, Ataxin-3 aggregation and neuronal dysfunction are reduced in vitro and in vivo. Furthermore, Ipo8 silencing was demonstrated to alleviate ataxic traits in vivo. Collectively, our findings indicate that Importin-8 may exert its protective effect by modulating NF-kb/p65 and Argonaute-2 proteins, also previously linked to MJD, standing as a promising therapeutic target to delay disease progression.

Argonaute-2

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged &#x2265;18 years) with type 2 diabetes (HbA1c &#x2265;8&#xb7;0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3&#xb7;9-5&#xb7;0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9&#xb7;57% for IcoSema and 9&#xb7;50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3&#xb7;32 vs -2&#xb7;44 percentage points; estimated treatment difference [ETD] -0&#xb7;88 percentage points [95% CI -1&#xb7;12 to -0&#xb7;63]), confirming superiority of IcoSema (p<0&#xb7;001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0&#xb7;79 vs 3&#xb7;81 kg; ETD -4&#xb7;61 kg [95% CI -5&#xb7;46 to -3&#xb7;75]), confirming superiority of IcoSema (p<0&#xb7;001). Rate of combined clinically significant (blood glucose <3&#xb7;0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0&#xb7;29 vs 0&#xb7;59 episodes per person-year of exposure; estimated rate ratio 0&#xb7;56 [95% CI 0&#xb7;32 to 0&#xb7;97]; p=0&#xb7;04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans

Association between anaemia and osteoporosis: a systematic review and meta-analysis.

BACKGROUND: Osteoporosis significantly impacts global morbidity. Recent evidence suggests anaemia may contribute to osteoporosis risk. This systematic review and meta-analysis investigates this association. METHODS: PubMed, Scopus, EBSCO, and ScienceDirect were searched for papers. Studies with definition of anaemia and assessing osteoporosis outcomes were included. Meta-analysis utilized random-effects models (DerSimonian-Laird method), and study quality was assessed via Newcastle-Ottawa Scale (NOS). Analyses were performed using R Studio. RESULT: Eighteen studies (861,540 participants) were analyzed. Anaemia significantly increased osteoporosis risk in univariate analysis (OR 1.62; 95% CI 1.33-1.98; p&#x2009;<&#x2009;0.001), despite high heterogeneity (I2 = 92.7%). The results remain significant in studies that reported multivariate analysis (OR 2.01; 95% CI 1.26-3.21; p&#x2009;=&#x2009;0.004). Sensitivity analyses confirmed the robustness of our result. CONCLUSION: Anaemia significantly associated with osteoporosis, emphasizing the need for targeted screening in anaemic individuals. Further studies should consider incorporating anaemia into osteoporosis and fracture prediction tools.

Humans

A Systematic Review of Lived Experiences of Receiving a Diagnosis of ADHD in Adulthood.

OBJECTIVE: With rising numbers of adults seeking and receiving ADHD diagnoses, understanding their first-hand experiences of the diagnostic process is key for sensitive support and service design. This systematic review collates, evaluates and synthesises the existing evidence-base on lived experiences of adult ADHD diagnosis. METHOD: Keyword searches of six databases generated 10,357 citations, which were subjected to a systematic screening process that identified 21 relevant studies. Findings were analysed using thematic synthesis. RESULTS: Analysis generated three overarching themes, elaborating how diagnostic experiences are shaped by adults' Relationship with Self, Relationship with Others, and Relationship with Systems. Personally, diagnosis was widely experienced as a pivotal identity event, triggering biographical reflection that could foster greater self-compassion, but also grief, anger and identity confusion. Socially, diagnosis facilitated interpersonal understanding and communication, but also exposed adults to stigma and introduced dilemmas about diagnostic disclosure. Systemically, adults experienced the diagnostic process as beset by barriers and delays, and reported highly variable access to post-diagnosis supports or treatment. CONCLUSION: Results suggest receiving an ADHD diagnosis in adulthood is a complex relational process that can be both validating and destabilising, with variation in experiences resulting from individual biographies, interpersonal resources, stigma climates, and service structures.

Humans

Review of regulatory requirements for benefit-risk assessment for medical devices: uncovering existing methodologies.

INTRODUCTION: A positive benefit-risk profile is a prerequisite for the market approval of medical devices. However, regulations are often criticized for providing limited information on benefit-risk assessment (BRA) despite growing expectations for quantitative methods. A clearer understanding of regulatory requirements, existing methodologies, and unresolved issues is needed. AREAS COVERED: Relevant regulatory documents referencing BRA for medical devices were systematically identified, with a primary focus on the European regulation followed by screening to extract BRA&#x2011;related requirements and any explicitly or implicitly described methods. The findings were analyzed and consolidated by BRA context, type, objective, methodological description, and implementation, thereby establishing a basis for the BRA methodological landscape. EXPERT OPINION: BRA is not a single concept, but a set of context&#x2011;dependent assessments across lifecycle of a medical device. BRA within clinical evaluation framed into BRAs of risk management holds a pivotal role and is supported by the most detailed methodological guidance, although BRAs in other contexts are important. A structured overview of existing BRA requirements clarifies their treatment across regulatory documents. By differentiating BRA contexts, types, objectives, and required methodological detail, the analysis supports a more transparent understanding of BRA and helps identify priorities for methodological refinement and interface clarification.

Risk Assessment

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype

Cross-species variant-to-function analyses implicate MEIS1 in conferring sleep abnormalities and impaired cerebellar development.

Genome-wide association studies (GWAS) have identified numerous loci for insomnia, yet functional validation of effector genes remains limited because most risk variants lie in noncoding regions, and the true causal gene is not known. Here, we use prior human cell-based variant-to-gene mapping to nominate six insomnia effector genes and test them in zebrafish, a tractable diurnal vertebrate model well suited for sleep phenotyping. Our CRISPR-based behavioral screening identifies the MEIS1 ortholog, meis1b, as a regulator of sleep maintenance, with crispants displaying impaired nighttime-specific sleep maintenance and increased sleep latency. Comparative chromatin analyses reveal conserved regulatory architecture spanning the human insomnia-associated locus and selectively implicate meis1b, whereas the duplicated ohnolog meis1a was dispensable. Developmental profiling further shows that meis1b is expressed in cerebellar granule progenitors, paralleling human MEIS1 expression, and that its disruption impairs cerebellar development. Together, these findings establish zebrafish as an efficient vertebrate platform for functional interrogation of GWAS candidates and support an evolutionarily conserved cerebellar role for MEIS1 in sleep maintenance.

Animals