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Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N&#x2248;1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age

Misalignment between ultra-processed status and 'better for you' claims on premix alcohol products.

BACKGROUND: Premix alcohol products (also known as ready-to-drink beverages) are a rapidly expanding alcohol category and frequently marketed using 'better for you' claims (e.g., 'Low sugar', 'Natural'). Little is known about the extent to which these products are ultra-processed or whether marketing claims align with ultra-processed status. This study aimed to address this evidence gap by auditing ingredient disclosure on premix products, assessing the ultra-processed status of these products, and determining the prevalence of 'better for you' claims with a particular focus on claims relating to ultra-processed status. METHODS: 534 premix alcohol products sold in major Australian retail outlets were assessed. Products were evaluated for compliance with mandatory ingredient disclosure, classified according to ultra-processed status based on the presence of indicators of ultra-processing (additives and other industrial ingredients), and analysed to determine the prevalence and types of 'better for you' marketing claims. RESULTS: Only 79% of assessed products displayed an ingredients list. Among compliant products, 98% contained at least one additive or ingredient indicative of ultra-processing, most commonly flavours, carbonating agents, colours, and sweeteners. One-third (33%) of products containing an ultra-processing indicator displayed a claim suggesting naturalness or minimal processing. Substantially higher proportions of ultra-processed products than non-ultra-processed products carried health-related claims. DISCUSSION AND CONCLUSIONS: Premix beverages available in Australia are overwhelmingly ultra-processed, yet many are marketed in ways that may mislead consumers about their composition and healthfulness. Stronger regulatory oversight of ingredient disclosure and marketing claims in this sector is urgently needed to support informed consumer decision-making.

Alcoholic Beverages

UV-based homogeneous disinfection process for removal of antibiotic resistance genes: Efficiency, mechanisms and influencing factors.

The proliferation and dissemination of antibiotic resistance genes (ARGs) in aquatic environments pose a serious threat to global public health. Ultraviolet-driven homogeneous advanced oxidation processes (UV-AOPs) represent a prospective suite of technologies for the efficient removal of ARGs. This review critically assesses recent advances in the application of UV-AOPs, specifically UV/hydrogen peroxide (UV/H2O2), UV/peracetic acid (UV/PAA), UV/persulfate (UV/PS), and UV/chlorine (UV/Cl), for the elimination of extracellular ARGs and intracellular ARGs. The underlying mechanisms involve direct ultraviolet-induced DNA damage, including pyrimidine dimer formation and strand breakage, as well as oxidation mediated by radicals such as hydroxyl radicals, sulfate radicals, carbon-centered radicals, and reactive chlorine species. The relative contribution of radical and non-radical pathways is strongly influenced by water chemistry and process conditions. We further expound on the critical operational and environmental factors governing ARG removal kinetics, including UV wavelength and fluence, oxidant type and dosage, ARG sequence characteristics, pH, ubiquitous anions, and dissolved organic matter, which collectively affect radical generation, quenching, and reaction microenvironments. Notably, for i-ARGs, UV-AOPs facilitate degradation not only through direct radical attack but also by disrupting cellular integrity and permeabilizing membranes, thereby enhancing the exposure of genetic materials to oxidative and photolytic damage. This review synthesizes current understanding to provide a mechanistic basis for the design and optimization of UV-AOP systems, highlighting their potential as effective barriers against the dissemination of antibiotic resistance in water reuse and purification scenarios.

Disinfection

Intervention components, training dose, and adherence in exercise-based prevention of hamstring strain injury in football: a systematic review and meta-analysis.

OBJECTIVE: To quantify associations between exercise-based prevention programmes and hamstring strain injury (HSI) risk in football participants, and whether training dose and adherence modify effects. METHODS: Six databases were searched to 1 October 2025. Randomised and cluster-randomised trials comparing HSI prevention programmes with usual practice or warm-up in football participants were included. Random-effects meta-analysis pooled risk ratios (RRs); subgroup analyses and meta-regression assessed effect modification. RESULTS: Fifteen trials (n = 7,465) were analysed. Programmes reduced HSI risk (RR = 0.51, 95% CI 0.36-0.71), with I&#xb2;=57% and a prediction interval crossing the null (0.18-1.40). Based on a control event rate of 7.8%, absolute risk reduction was 3.8% (38 fewer HSIs per 1000 participants; 95% CI 23-50 fewer). Effects were stronger for shorter interventions (1-6 months; RR = 0.43) than longer interventions (7-10 months; RR = 0.77; P for interaction=0.04), and for elite/semi-professional players (RR = 0.38) than amateur players (RR = 0.77; P for interaction = 0.02). Training frequency and weekly volume did not modify effects, whereas adherence did. High adherence (&#x2265;75%) was associated with lower HSI risk (RR = 0.36, 95% CI 0.28-0.48), whereas low adherence (<75%) showed no clear benefit (RR = 0.92, 95% CI 0.68-1.23; P for interaction <0.00001). Each 10% increase in adherence corresponded to an RR multiplier of 0.83 (approximately 17% lower RR). Certainty of evidence was low. CONCLUSION: Exercise-based programmes reduce HSI risk in football when implementation supports sustained adherence. Effects may be stronger in shorter interventions and elite populations, but evidence remains insufficient to differentiate programme types or components.

Humans

Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli across humans, poultry and wastewater sectors in Douala, Cameroon.

BACKGROUND: The global health threat of antimicrobial resistance involves the human, animal and environmental sectors. Data from Cameroon are scarce. OBJECTIVES: This study aimed to define extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) rates and associated risk factors across the three sectors in Douala, Cameroon, and to define molecular characteristics of isolates. METHODS: From June 2022 to May 2023, we collected blood cultures from hospitalized patients, rectal swabs from healthy pregnant women, caeca from broiler chickens and environmental wastewater. Samples were screened for ESBL-Ec using CHROMAgar&#x2122; ESBL and cefotaxime-supplemented Tryptone Bile X-glucuronide agar. Antimicrobial susceptibility testing was performed by disk diffusion following EUCAST guidelines. Whole-genome sequencing was carried out using Illumina technology. RESULTS: Of 628 samples, 374 yielded ESBL-Ec. Prevalence was 54.6% (131/240) in pregnant women, 70.4% (169/240) in chickens and 93.1% (67/72) in wastewater. The proportion of ESBL-Ec among E. coli-positive-blood cultures was 9.2% (7/76). Multi-family household living was independently associated with ESBL-Ec carriage among pregnant women (adjusted odds ratio&#x200a;=&#x200a;1.7, 95% CI 1.0-3.1, P&#x200a;=&#x200a;0.03). High co-resistance (>70%) was observed for tetracycline, ciprofloxacin and trimethoprim/sulfamethoxazole. Sequencing of 32 isolates revealed 45 distinct resistance genes, including blaCTX-M-15 (n&#x200a;=&#x200a;13, 40.6%), blaCTX-M-55 (n&#x200a;=&#x200a;11, 34.4%) and last-resort antibiotic resistance genes mcr-1 and bla OXA-181. High-risk sequence types included ST131 (pregnant women) and ST10 (chickens). Notably, ST48 was shared between pregnant women and chickens, and ST155 between pregnant women and wastewater. CONCLUSION: Cross-sectoral ESBL-Ec in Douala exhibits high genomic diversity and alarming resistance. The occurrence of last-resort genes requires immediate One Health surveillance and coordinated interventions.

Journal Article

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals

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&#x2009;=&#x2009;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

Effects of music interventions on seizure outcomes in people with epilepsy: a systematic review and meta&#x2011;analysis.

OBJECTIVES: To evaluate effects of music interventions on seizure outcomes in people with epilepsy. METHODS: We performed a systematic review and meta&#x2011;analysis of controlled and single&#x2011;arm studies. Searches were conducted in four English databases, two trial registries, and three Chinese databases, up to October 11, 2025. Dichotomous outcomes were pooled as odds ratios (ORs) and continuous outcomes as mean differences or standardized mean differences (SMD, Hedges' g) using random&#x2011;effects models. Heterogeneity was assessed with Cochran's Q and I2. Preplanned subgroup and leave&#x2011;one&#x2011;out sensitivity analyses examined control type and study influence. Risk of bias and evidence certainty were appraised. RESULTS: Fifteen studies were included. Single&#x2011;arm syntheses suggested benefit: pooled curative&#x2011;effect rate 0.715 (95&#xa0;% CI 0.584-0.846) and pre-post IED reduction -0.51 (95&#xa0;% CI -0.88 to -0.13). Controlled between&#x2011;group estimates were imprecise and heterogeneous. Pooled OR for seizure response was 2.71 (95&#xa0;% CI 0.61-12.12, I2&#xa0;=&#xa0;81.2&#xa0;%, p&#xa0;=&#xa0;0.19). IED responder OR was 4.57 (95&#xa0;% CI 0.84-24.86, I2&#xa0;=&#xa0;68.9&#xa0;%). IED frequency SMD was -1.48 (95&#xa0;% CI -3.06 to 0.10, I2&#xa0;=&#xa0;95.2&#xa0;%). Seizure&#x2011;frequency SMD across controlled studies was -0.004 (95&#xa0;% CI -1.772 to 1.763, I2&#xa0;=&#xa0;95.6&#xa0;%). Results were sensitive to individual studies and limited by small samples and variable comparators. CONCLUSIONS: Music interventions show promising within&#x2011;study effects on seizure outcomes, but controlled evidence is inconclusive due to high heterogeneity and imprecision. High&#x2011;quality, adequately powered randomized trials with standardized interventions and matched active controls are needed.

Humans

Aortoesophageal Fistula: Mending the Lethal Connection-A Systematic Review and Meta-Analysis.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare, life-threatening condition with limited high-quality evidence to guide management. METHODS: We conducted a systematic review and meta-analysis of PubMed and Scopus through December 2025, evaluating survival and complication outcomes according to treatment strategy and morphological severity. Patients were categorized into 5 groups: TEVAR alone, staged TEVAR followed by surgery, primary open or hybrid surgery, TEVAR with esophageal stenting, and supportive/palliative care. Outcomes were pooled as proportions with 95% confidence intervals (CIs). RESULTS: A total of 167 reports representing 528 patients were included. Overall 30-day mortality was 31.2% (95% CI 27.0% to 35.7%) and 1-year mortality 41.2% (95% CI 36.2% to 46.4%). Infection occurred in 32.6%, reintervention in 20.2%, and recurrence in 13.2%. Staged TEVAR followed by surgery showed favorable survival (30-day 12.7%, 1-year 26.1%) but high infection (66.7%) and reintervention (43.2%) rates. TEVAR with esophageal stenting had the lowest early mortality (5.0%) but frequent reintervention (54.5%) and 1-year mortality of 33.3%. TEVAR alone demonstrated the lowest 1-year mortality among definitive strategies (25.5%) but notable recurrence (26.9%). Primary open or hybrid surgery carried higher early and late mortality, while supportive/palliative care had the worst outcomes. Morphological severity correlated strongly with mortality, infection, reintervention, and recurrence, with type IV lesions showing particularly poor prognosis. CONCLUSION: Despite contemporary management, AEF carries high early and late mortality. Definitive strategies, particularly staged TEVAR followed by surgery, offer improved survival but increased complications. Morphology-guided, individualized management is recommended.

Adult

Does Inquiry-Based Learning Improve Students' Critical Thinking? A Meta-Analysis Accounting for Control Group Variations.

BACKGROUND: Inquiry learning is widely recognized, through empirical studies, as an appropriate instruction in enhancing students' critical thinking, yet the results were varied across context. The previous meta-analysis did not include the control group variations as a potential moderator and the studies subject domain was limited only to science subjects. Consequently, it is difficult to generalize the effectiveness of IBL in enhancing critical thinking. This meta-analysis aims to investigate whether inquiry learning is effective in improving the students' critical thinking skills and examine the moderating roles of each study characteristic. Methods The literature search applying the PRISMA protocol 2020 was conducted by utilizing SCOPUS, ERIC, and DOAJ databases. A total of 57 studies from 51 articles, published from 2015 to 2025, were synthesized using a random-effects model with standardized mean difference (SMD). RESULTS: The analysis revealed that IBL has a large and significant effect on enhancing students' critical thinking (g&#xa0;=&#xa0;1.336; 95% CI [1.061, 1.611]). However, substantial heterogeneity was observed (I 2&#xa0;=&#xa0;92.09%), suggesting variability across contexts. Moderator analyses revealed that the main moderator, control group variations, was statistically significant in moderating the effectiveness of IBL (Qm&#xa0;=&#xa0;5.21; p&#xa0;=&#xa0;.022). in contrast, subject domain (Qm&#xa0;=&#xa0;1.43; p&#xa0;=&#xa0;.698), education level (Qm&#xa0;=&#xa0;1.11; p&#xa0;=&#xa0;.774), and country ( Q m &#xa0;=&#xa0;3.33; p&#xa0;=&#xa0;.650), were insignificantly moderating the effectiveness of inquiry learning. CONCLUSIONS: The present meta-analysis highlighted that IBL is effective in improving students' critical thinking. However, the effectiveness of IBL was relative to the type of control group variations. Its effect on critical thinking was greater when compared with teacher-centered learning but smaller when compared with other student-centered learning.

Thinking

ReMeDy: A Flexible Statistical Framework for Region-Based Detection of DNA Methylation Dysregulation.

Region-based epigenome-wide association studies have demonstrated improved statistical power and biological interpretability compared with probe-wise analyses of DNA methylation data. However, most existing region-based methods characterize methylation dysregulation primarily through changes in mean methylation levels associated with a phenotype of interest. Substantial evidence indicates that phenotype-associated methylation alterations may also manifest through changes in methylation variability or through joint shifts in mean and variability. Despite this, no existing statistical framework jointly models mean-variance methylation changes in a region-based manner. We propose ReMeDy, a flexible statistical framework that uses a hierarchical likelihood approach within a generalized linear model setting to identify differentially methylated regions, variably methylated regions, and regions exhibiting joint differential and variable methylation at a genome-wide scale. Unlike existing models, ReMeDy operates directly on biologically defined co-methylated regions, allowing it to naturally capture spatial correlation inherent in DNA methylation array data, while avoiding reliance on heuristic, user-defined tuning parameters such as smoothing spans and kernel bandwidths that can substantially influence results and introduce subjectivity. Through extensive simulation studies and comprehensive benchmarking against popular models, we demonstrate that ReMeDy maintains false discovery and Type-I error rates at nominal levels while achieving consistently higher statistical power across a wide range of realistic scenarios. Application to population-level DNA methylation data further shows that ReMeDy identifies biologically meaningful regions and pathways implicated in complex human diseases that are not captured by conventional mean-based analyses alone. ReMeDy is implemented as an open-source R package and is freely available at https://github.com/SChatLab/ReMeDy.

DNA Methylation

The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.

PURPOSE: No prior systematic review has specifically evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) in improving both psychological and physical outcomes among cancer populations. This study aims to assess MBCT's effects on cancer patients' mental and physical health. METHOD: Following PRISMA guidelines and with PROSPERO registration (CRD42023453581), we systematically searched PubMed, Cochrane CENTRAL, Embase, and Web of Science for randomized controlled trials (RCTs) were searched up to June 2026. Eligible trials enrolled adults (&#x2265; 18&#xa0;years) with any cancer type/stage, compared MBCT delivered per standard manual against non-MBCT controls, and reported at least one validated measure of distress, depression, or anxiety; secondary outcomes included fatigue, quality of life, and mindfulness skills. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the Cochrane tool; random-effects meta-analyses were performed in Stata 16. RESULTS: 11 RCTs comprising 1122 participants (mean age 54.8&#xa0;years; 91% female) were included. MBCT produced large, significant reductions in psychological distress (SMD&#xa0;=&#xa0;-0.81, 95% CI-1.27 to-0.40), depression (SMD&#xa0;=&#xa0;-0.95, 95% CI -1.40 to-0.49), and anxiety (SMD&#xa0;=&#xa0;-0.86, 95% CI -1.22 to-0.51). It also markedly decreased fatigue (SMD&#xa0;=&#xa0;-0.83, 95% CI-1.10 to-0.56), improved quality of life (SMD&#xa0;=&#xa0;0.56, 95% CI 0.22-0.88), and enhanced mindfulness skills (SMD&#xa0;=&#xa0;0.76, 95% CI 0.59-0.92). CONCLUSIONS: This meta-analysis is the first to exclusively synthesize RCT evidence of standardized MBCT in cancer care, demonstrating significant dual benefits for emotional and physical well-being while providing strong support for integrating MBCT into comprehensive oncology rehabilitation.

Humans

Contribution of the Arg-33-His replacement in the histidine kinase CpxA to carbapenem and cefiderocol resistance in Serratia marcescens.

OBJECTIVE: The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all &#x3b2;-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS: The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS: Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS: This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

Cefiderocol

An Integrated Proteomics and Genomics Approach to Identify Essential Protein Kinases During Human Trophoblast Development.

In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKC&#x3b6; are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy.

Humans

The application of artificial intelligence in healthcare practice: A mapping review of systematic reviews.

Artificial intelligence (AI) is rapidly transforming healthcare practice, with growing evidence supporting its use in diagnosis, prognosis, treatment planning, and operational decision-making. The proliferation of systematic reviews in recent years underscores the need for an updated synthesis of the literature to inform research, policy, and practice. We searched PubMed, Web of Science, Scopus, IEEE Xplore, and CINAHL for systematic reviews and meta-analyses published between 2019 and February 2026. Eligible reviews focused on AI applications in healthcare practice, were peer-reviewed, and written in English. A total of 368 reviews met the inclusion criteria. Publication volume increased steadily, peaking in 2025. AI research was concentrated in high-density domains, such as radiology, oncology, and critical care. Across reviews, diagnostic imaging, electronic health record (EHR) data, and biomarkers/laboratory results accounted for 68% of training data sources, though newer data types, such as wearable device and sensor data, emerged from 2022 onward. Diagnosis, prognosis, and treatment comprised over 80% of AI applications, with novel uses emerging in recent years, such as AI-assisted clinical documentation (e.g., ambient documentation tools) and patient education. Ethical concerns were reported in 78.5% of reviews, with privacy, model accuracy, data and algorithmic bias, and explainability as recurrent themes. The proportion of reviews reporting ethical concerns increased from 2021 to 2025. AI applications in healthcare are expanding in scope, diversifying in data sources, and evolving toward novel clinical and operational uses. The human-centered AI or augmented intelligence paradigm, integrating computational precision with clinical expertise, holds significant promise but will require parallel advances in governance, regulatory frameworks, and ethical oversight to ensure safe adoption.

Artificial Intelligence

Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.

PURPOSE: Neoadjuvant chemotherapy (NACT) is a commonly recommended approach for treating several cancers, and improving patients' outcomes to this therapy is important. This systematic review and meta-analysis assessed the impact of exercise on pathologic complete response (pCR), a key short-term marker of treatment efficacy, in patients with solid tumors receiving NACT. METHODS: Four electronic databases were searched for randomized controlled trials with physical exercise during NACT as an intervention published until May 2025. Risk of bias was assessed using Cochrane RoB 2.0 and the TESTEX scale. A random-effect meta-analysis using the inverse variance method synthesized the results. Heterogeneity was assessed using I2 and chi2 statistics. Risk ratio estimated the effect size. RESULTS: Eight studies involving 504 patients with breast, esophageal, gastric, or rectal&#xa0;cancer were included in the final analysis. Exercise interventions consisted of aerobic and resistance exercise. Overall, there were no significant differences between exercise and control groups in the rate of pCR to NACT (pooled risk ratio: 1.08 (95% CI: 0.82 to 1.43) Z&#x2009;=&#x2009;0.56, p&#x2009;=&#x2009;0.58). However, meta-regression data from breast cancer (BC) studies (4 studies, 367 participants) suggest exercise may be associated with enhanced tumor response to NACT in HR&#x2009;+&#x2009;/HER2- subtypes (regression coefficient: 0.83 (95% CI: -0.00 to 1.67), p&#x2009;=&#x2009;0.05). CONCLUSION: Exercise during NACT did not improve pCR across cancer types. Exploratory meta-regression findings suggest a possible benefit of exercise in BC patients with the HR&#x2009;+&#x2009;/HER2- subtype. These results should be interpreted with caution due to the small number of studies and low certainty of the evidence.

Humans

Less Invasive Surfactant Administration Using Video Laryngoscope to Decrease Pain in Neonates: A Randomized Controlled Trial.

OBJECTIVES: To assess whether the use of video laryngoscope, when compared to conventional laryngoscope decreases pain (assessed by Faceless Acute Neonatal Pain Scale) in preterm neonates while administering surfactant by LISA. METHODS: Preterm neonates <&#x2009;35 weeks requiring FiO2&#x2009;>&#x2009;0.3 on CPAP pressure of at least 6&#x2009;cm of H2O were administered surfactant by LISA technique either by video laryngoscope (Intervention) or conventional laryngoscope (Control). Faceless Acute Neonatal Pain Scale was used to determine pain 5&#x2009;min before the procedure, immediately, 5&#x2009;min, and 10&#x2009;min after the procedure. The primary outcome was severity of pain; secondary outcomes were time taken to complete the procedure, number of attempts, incidence of IVH, and adverse events during the procedure. RESULTS: In total, 42 neonates of <&#x2009;35 weeks gestation with comparable baseline demographics were randomized into 2 groups. The median (IQR) FANS score immediately post-procedure in the intervention arm was 2 (2-4) versus 2 (1-4) in the control arm, p&#x2009;=&#x2009;0.79. There was no statistical difference in the secondary outcomes studied. CONCLUSION: The two groups had no difference in the pain score. The pain experienced by neonates during the LISA procedure was moderate and of short duration and it did not depend on the type of laryngoscope used. Moderate pain during the procedure can be managed with nonpharmacological measures; thereby, the use of sedatives or analgesics can be avoided, which might be of concern. There was no difference in the number of attempts or in time taken to complete the procedure when performed by neonatologists experienced in using conventional laryngoscopes compared to video laryngoscopes. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2022/09/045204 on 05.09.2022.

Humans

Immunogenicity and safety of inactivated TZ84- vs. HM175-based hepatitis A vaccines in pediatric populations: A systematic review and meta-analysis.

Individual studies indicate stronger and persistent long-term immunogenicity with TZ84-based than HM175-based hepatitis A vaccines. This systematic review and meta-analysis compared immunogenicity and safety of inactivated TZ84- and HM175-based hepatitis A vaccines in children and adolescents. Studies involving adults, immunocompromised populations, non-comparative designs, non-English publications, and studies with non-extractable outcomes were excluded. MEDLINE/PubMed, Google Scholar, other electronic databases, and grey literature were searched (September-October 2025). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and meta-analyses were performed where appropriate. Seven publications arising from four randomized cohorts (total participants: 3,282) reporting seroconversion rates (SCRs), geometric mean concentrations (GMCs), long-term seroprotection, and adverse events (AEs) were identified. Pooled analyses demonstrated higher SCRs and GMCs with TZ84 than HM175-based vaccines following both one and two doses. SCRs at 1&#x2009;month [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.88-4.96] and GMCs at 7&#x2009;months [standardized mean difference (SMD): 0.88; 95% CI: 0.18-1.58; p&#x2009;=&#x2009;.01] both favored TZ84-based vaccines. Long-term follow-up (up to 186&#x2009;months/15.5 y) showed higher reported anti-HAV antibody concentrations for TZ84-based vaccines. The AEs were comparable between vaccine types (RR: 0.95; 95% CI: 0.76-1.20; p&#x2009;=&#x2009;.69). Evidence was limited by the small number of unique randomized cohorts, geographic concentration in China, heterogeneity across studies, and reliance on surrogate immunogenicity outcomes. Overall, available evidence suggests that TZ84-based hepatitis A vaccines (HAPIBEV&#x2122;/HEALIVE&#xae;) are associated with higher reported antibody responses and greater reported antibody persistence than the HM175-based vaccine (HAVRIX&#xae;) in children and adolescents, with comparable safety profiles.Registration: PROSPERO CRD420251154480.

Humans