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Orofacial Cleft Disparities in American Indian and Alaska Native Populations: A Systematic Review and Meta-Analysis.

ObjectiveTo evaluate the prevalence, access to care, and health outcomes of orofacial clefts (OFCs) among American Indian and Alaska Native (AI/AN) populations through a systematic review and meta-analysis.DesignSystematic review and meta-analysis performed in accordance with PRISMA 2020 guidelines and registered with PROSPERO (CRD420251035364).SettingUS-based population registries, hospital databases, and institutional or community-level retrospective studies involving AI/AN populations.Patients and ParticipantsAI/AN individuals with OFCs compared with non-Hispanic White patients.InterventionsPrimary cleft lip and palate repair, secondary cleft-related procedures, and multidisciplinary cleft care.Main Outcome Measure(s)Prevalence of OFCs, timing of cleft surgery, discharge disposition, access to specialists, and qualitative determinants of disparities.ResultsEighteen studies including more than 1985 AI/AN patients were identified. Meta-analysis of 5 studies estimated a pooled OFC prevalence of 15 per 10 000 live births (95% confidence interval: 5-49), with substantial heterogeneity (I2 = 99.8%). Individual studies reported significantly higher OFC prevalence in AI/AN populations compared to non-Hispanic Whites (odds ratio range: 1.44-2.68). Geographic maldistribution of craniofacial-trained surgeons, increased odds of nonhome discharge, and delayed cleft palate repair were consistently observed barriers. Qualitative analyses highlighted structural inequities, perceived racism, and lack of culturally responsive care as major contributors to disparities.ConclusionsAI/AN populations face a disproportionately high burden of OFCs alongside structural barriers to timely, culturally competent care. Addressing these disparities requires community-engaged, multidisciplinary interventions that improve geographic access and integrate culturally responsive approaches to care.

Humans

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2  = 97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2  = 97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

Humans

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans

Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n = 32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n = 4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

Humans

Comparative in silico analysis of Apis mellifera immune responses to Varroa destructor and Tropilaelaps mercedesae: Common and mite-specific molecular signatures.

Parasitic mites Varroa destructor and Tropilaelaps mercedesae represent major threats to global honey bee (Apis mellifera) health and productivity, yet comparative molecular insights into host responses remain limited. To address this, we systematically compiled published studies (2015-2025) reporting genes associated with honey bee interactions with V. destructor (11 studies, 87 genes), T. mercedesae (4 studies, 35 genes), and hygienic behavior (6 studies, 44 genes). Gene identifiers were harmonized to the Amel_HAv3.1 genome assembly, yielding three non-redundant sets: 64 Varroa-associated, 34 Tropilaelaps-associated, and 44 hygienic behavior-associated genes. Venn analysis identified 10 overlapping genes (including A0A088A8D5, A0A088ADL8, ABAE_APIME, Def1, Def2, Gapdh, HYTA_APIME, Imd, LOC726783, and Vg), suggesting conserved defense mechanisms, while 41 and 24 genes were uniquely associated with Varroa and Tropilaelaps, respectively. Enrichment analyses revealed Varroa-responsive genes were enriched in immune processes, chitin catabolism, and signaling pathways (Toll/Imd, MAPK, Wnt). Tropilaelaps-associated genes were enriched for antibacterial defense and stress response, with Toll/Imd signaling as the sole significantly enriched pathway. Overlapping genes reinforced core innate immunity activation. Protein-protein interaction network centrality analysis identified key hub genes: Def1, HYTA_APIME, ABAE_APIME, PPO, Imd, PGRP-LC, Vg for Varroa; and ACPH1_APIME, MRJP1, Vg, LOC726783 for Tropilaelaps. Results demonstrate that, despite differences in mite biology, honey bees show a conserved immune response against both parasites, centered on antibacterial defense, humoral immunity, and activation of the Toll/Imd pathway. Although limited by the in-silico nature and research asymmetries reflecting Tropilaelaps' emergence, this curated resource establishes a comprehensive framework for elucidating shared and distinct molecular defense mechanisms. Ultimately, this approach prioritizes diagnostic markers and candidate genes for functional validation and breeding strategies to enhance colony resilience against mite‑driven disease globally.

Animals

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5 mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea

A therapeutic atlas of monogenic inflammatory bowel disease.

BACKGROUND AND AIMS: Evidence-based, mechanism-guided therapies are urgently needed for treating monogenic inflammatory bowel disease (mIBD). For such rare diseases, mechanistic insight is essential to guide treatment when conventional clinical trials are often not feasible. We aimed to summarize literature-based evidence and to identify knowledge gaps. METHODS: We conducted a systematic review of published manuscripts evaluating the therapeutic efficacy in mIBD. We quantified and compared the global therapeutic response score across treatments and conditions. In a subset of conditions, biomarkers of longitudinal therapeutic response were evaluated in comparison to non-monogenic pediatric IBD cohorts. RESULTS: Responses to 35 therapeutics across the 102 known genetic causes of mIBD were evaluated in 241 articles and 669 patients, summarizing 302 gene-drug responses. The efficacy of at least one pharmacological intervention was identified in 61% (n = 62/102) of the mIBD conditions, highlighting a major unmet need for effective medications in many others. Gene- and pathway-specific responses were demonstrated for several therapies, including allogeneic hematopoietic stem cell transplantation, gene therapy, and advanced therapies such as anti-TNF agents, IL-1 inhibitors, mTOR inhibitors, as well as eculizumab in CD55 deficiency, abatacept in CTLA4 deficiency, and the immunometabolic agent empagliflozin in glycogen storage disease type 1b. CONCLUSIONS: This study highlights the potential of precision medicine approaches tailored to genetic and pathway-specific mechanisms, while underscoring the urgent need for effective therapies in many monogenic conditions that remain without established treatment options.

Humans

Ten years on, still out of reach: barriers to PrEP access and retention in France according to frontline actors (QualiPrEP Study).

Pre-exposure prophylaxis (PrEP) for HIV has been available in France since 2014, and reimbursed since 2016, with general practitioners allowed to prescribe it since 2021. Despite these policy advances, uptake remains low among some of the most affected populations. This community-based qualitative study explored barriers to PrEP access and retention ten years into its implementation.Interviews were conducted with 28 PrEP frontline actors (healthcare professionals and community-based workers involved in promoting, prescribing, or supporting PrEP). The sample included one group discussion (n = 5), two triads (n = 6), two dyads (n = 4), and nine individual interviews (n = 13). Thematic analysis was inductive, with barriers classified across four main domains.Participants were mostly cisgender men, median age 48, born in France and abroad, and employed by NGOs in Paris. Thirteen barriers and four major themes emerged: (1) Internal psychosocial barriers: lack of knowledge, negative health-related reactions; HIV stigma; STI risk perception, taboos; (2) Internal pragmatic barriers: perceived limits of protection, usage and follow-up constraints; (3) External psychosocial barriers: limited physician knowledge and reluctance; (4) External pragmatic barriers: communication failures; structural constraints, lack of human and financial resources.Findings call for more targeted messaging, simplified care models and provider training. They highlight the need to address social and symbolic dimensions of PrEP, with insights from those supporting users to ensure more equitable implementation.

Humans

Efficacy of transcranial alternating current stimulation for musculoskeletal pain and sleep quality: a systematic review and meta-analysis.

BACKGROUND: Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique, emerging as a potential therapeutic option for musculoskeletal pain management. OBJECTIVE: To comprehensively evaluate the efficacy and safety of tACS for alleviating pain and improving sleep quality in adults with musculoskeletal pain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Seven major databases and other sources were searched from inception until April 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias. A random-effects model was used to pool standardized mean differences (SMDs). The certainty of evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation framework. RESULTS: Six RCTs involving 232 participants were included. Meta-analysis showed that tACS could significantly reduce pain intensity compared to control (SMD = -0.355, 95% CI: -0.625 to -0.084, p = 0.010, I² = 28.7%). However, no significant improvement was found for sleep quality (SMD = 0.004, 95% CI: -0.310-0.317, p = 0.982, I² = 0.0%). Adverse effects were mild and transient, comparable to sham stimulation. The overall certainty of evidence was rated as low for both pain and sleep quality outcomes. CONCLUSION: Current evidence suggests that tACS may be beneficial for musculoskeletal pain; however, the available evidence remains limited and should be interpreted cautiously. The effect of tACS on sleep quality remains uncertain because of the limited number of available studies. Future well-designed RCTs with standardized outcome measures, condition-specific stimulation protocols, and longer follow-up are required to establish the efficacy and long-term safety of tACS.

Humans

Performance of Automated Hematology Analyzer Criteria in Detecting Peripheral Blood Smear Abnormalities: A Systematic Literature Review.

OBJECTIVES: Criteria for visual examination of stained peripheral blood smear (PBS) differ among institutions in the United States and internationally. In an effort to standardize review criteria, the International Consensus Group for Hematology Review (ICGHR) proposed in 2005 a consensus list of rules for CBC findings that should trigger a review of automated cell counter results and potentially lead to further testing or blood smear review. The primary aim of this paper is to report on the published literature in the past 20 years regarding PBS review criteria and their ability to identify relevant peripheral blood abnormalities. METHODS: We performed a systematic review of the published literature from 2005 to 2025 to investigate and summarize PBS review criteria and performance in the context of automated hematology analyzers in clinical laboratories. RESULTS: Of 5351 citations, 68 studies met our search criteria. These studies included 22 countries and all major hematology analyzer manufacturers. Marked variability was observed in study populations, analyzer flagging criteria, details of PBS visual review, definitions of a "positive" smear, and approaches to statistical data analysis. Across studies, the blast flag sensitivity ranged from 18% to 100% while the blast flag specificity ranged from 17% to 100%. Wide ranges in sensitivity/specificity were also seen for atypical and/or abnormal lymphocyte flags across studies. For studies analyzing the same patient population, less striking variation was seen across instruments. CONCLUSIONS: This systematic review provides a 20-year overview of the literature, highlighting significant variability in PBS review criteria, dependence on study design and hematology analyzer, and the importance of developing harmonized evidence-based guidelines.

Humans

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans

The impact of artificial intelligence on critical thinking and clinical reasoning in health professions education: A systematic review and meta-analysis.

BACKGROUND: Critical thinking and clinical reasoning underpin healthcare professionals' ability to navigate uncertainties and deliver safe and effective care. With artificial intelligence (AI) advancement and growing adoption, AI-based educational tools are increasingly used to support these cognitive competencies' development. OBJECTIVE: To synthesize randomised and controlled clinical trials on AI-based educational tools in health professions education and examine their effects on critical thinking and clinical reasoning among health professions students. METHODS: Six electronic databases were searched from January 1, 2014 to July 28, 2025 was reviewed: PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, Embase and Web of Science. Two independent reviewers performed data extraction and quality assessment using standardized JBI checklists. The GRADE approach was used to assess the certainty of evidence. Studies were pooled via random-effects meta-analyses or narrative syntheses. RESULTS: Fourteen randomised controlled trials and seven controlled clinical trials were included (n&#xa0;=&#xa0;21). Meta-analyses revealed small to medium effect sizes for the surrogate clinical reasoning outcomes of performance-based assessment scores (SMD 0.68; 95% CI [0.38, 0.98], p-value&#xa0;=&#xa0;0.00; I2&#xa0;=&#xa0;38%) and knowledge test scores (SMD 0.39; 95% CI [0.09, 0.69], p-value&#xa0;=&#xa0;0.01; I2&#xa0;=&#xa0;79%). Critical thinking and clinical reasoning skills and dispositions were narratively synthesized, with majority of included studies favouring AI-based interventions but the evidence had low to very low certainty. CONCLUSION: AI-based educational interventions may improve critical thinking and clinical reasoning among health profession students, but the evidence is very uncertain. This review offers preliminary insights but does not allow identification of optimal interventions or discipline-specific recommendations due to small sample sizes and substantial intervention heterogeneity. Further research is required to draw definitive conclusions. PROTOCOL REGISTRATION: CRD42025634074.

Humans

Mediators of the Association Between a Parent's Experience of Trauma and Their Children's Well-Being: A Systematic Review.

At present, our understanding of trauma's complexity is underdeveloped, particularly with regard to intergenerational effects. In this paper, we review peer-reviewed literature on parental trauma and child well-being, focusing on mediating factors. We conducted a global systematic review of longitudinal, observational studies assessing mediators between a parent's traumatic exposure and their children's well-being. The primary outcome of the review was quantitative measures of child well-being (physical and psycho-social) assessed when the child was 18&#x2009;years or under. We considered the following experiences as trauma exposures: intimate partner violence, rape, sexual assault, victimization during violent crime, childhood abuse, and exposure to direct, immediate threats to personal survival during war, political unrest, natural disasters, and sudden, critical injury/illness. Thirty-two studies met our inclusion criteria. The two most common mediator categories were caregiver mental health (n&#x2009;=&#x2009;13) and parenting behavior (n&#x2009;=&#x2009;10). Other studies measured aspects of the parent-child relationship (n&#x2009;=&#x2009;9), maternal stress factors (n&#x2009;=&#x2009;5), parental physical health (n&#x2009;=&#x2009;2), and child-level factors (n&#x2009;=&#x2009;6) as mediators. Almost all included studies (n&#x2009;=&#x2009;28) detected a mediation effect. The majority of studies (n&#x2009;=&#x2009;21) cited robust theoretical frameworks to support their mediator and outcome choices. Studies varied in quality, but most used appropriate, formal mediation analyses. Several study designs could be enhanced by methods to improve precision and reduce bias. Currently, there is little consistency in how similar constructs are measured between mediation studies. We did not locate any studies in low-income countries, and few studies examined aspects of family dynamics, physical health, environmental characteristics, or paternal factors.

Humans

Implementation of a Face-To-Face Vs Virtual Peer-Integrated Collaborative Care Intervention for Mental Health Treatment of Physical Trauma Survivors: A Qualitative Study of Lessons from the COVID-19 Pandemic.

OBJECTIVE: We assessed the impact of the COVID-19 pandemic on the implementation of a peer-integrated enhancement of integrated clinical care intervention to address the mental health needs of 450 patients undergoing treatment for a physical injury. METHODS: Qualitative data were collected by 7 clinician investigators of a randomized controlled trial acting as participant observers in a trauma care setting of a major U.S. metropolitan hospital and analyzed in collaboration with an external mixed methods specialist. RESULTS: The pandemic created or exacerbated several implementation barriers, including increased risk of infection, homelessness, hospitalizations and comorbid conditions such as fentanyl overdoses that increased demand on emergency department and Trauma Center services, imposition of safety measures to reduce risk of infection in clinical settings, transition from face-to-face to virtual interactions with study patients, shortages of specialty mental health providers, suspension of recruitment of patients into the study, scheduling calls with patients, and an increased workload for the study clinical interventionists. Peer specialists perceived the transition to virtual interactions with patients reduced their effectiveness; however, this was not reflected in assessments of patient satisfaction with services received and may have inadvertently increased adoption by Trauma Center staff. Reduction in reach of the intervention to target population was temporary. CONCLUSIONS: The COVID-19 pandemic exacerbated existing barriers and created new barriers to successfully implementing evidence-based practices in trauma care settings, resulting in an attenuation of their effectiveness. However, the shift from face-to-face to virtual services delivery may have actually led to improved implementation outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03569878. Registered June 15, 2018.

Humans

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N&#xa0;=&#xa0;54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms &#x2265; 2-3&#xa0;days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64&#xa0;years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65&#xa0;years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans