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PubMed2026

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans↗

PubMed2026

Impact of PerioperAtive LidocAine Infusions on Enhanced Recovery After Noncardiac Surgery (IMPALA-ERAS) in an inpatient setting: rationale, design and protocol for a sequential, repeated crossover trial.

INTRODUCTION: Multimodal analgesic strategies designed to minimise perioperative opioid exposure are fundamental components of enhanced recovery after surgery (ERAS) pathways. Despite widespread implementation of ERAS protocols, the optimal analgesic regimen remains undefined, as the individual contributions of specific agents to overall analgesic efficacy and opioid-sparing effects are not fully elucidated. Intravenous lidocaine, a widely utilised local anaesthetic, possesses both analgesic and anti-inflammatory properties and has been associated with improved gastrointestinal recovery. This study seeks to pragmatically evaluate the impact of incorporating perioperative intravenous lidocaine infusion into established ERAS pathways on postoperative functional recovery. METHODS AND ANALYSIS: The Impact of PerioperAtive LidocAine Infusions (IMPALA) on ERAS trial is a single-centre, pragmatic, cluster-randomised, double-blinded, placebo-controlled study. A total of 2290 patients undergoing elective colorectal surgery, emergency general surgery, urology, ventral hernia repair, surgical oncology or spine surgery will be randomly assigned to receive either intraoperative and postoperative intravenous lidocaine infusions (administered for up to 48 hours) or placebo as part of a standardised multimodal analgesic regimen integrated into established ERAS pathways. The primary outcome is case mix index-adjusted resource length of stay, defined as the time interval from surgical initiation to hospital discharge adjusted for case mix index. The primary outcome is total inpatient opioid consumption within the first 72 hours, reported in oral morphine milligram equivalents. Secondary outcomes include various in-hospital clinical endpoints derived from the electronic health record. ETHICS AND DISSEMINATION: This protocol and accompanying statistical analysis plan outline the study design, primary and secondary endpoints and analytic methodology. The IMPALA-ERAS trial has received ethical approval from the Vanderbilt University Institutional Review Board (IRB: 250617). The findings will be disseminated via peer-reviewed publications and presentations at national conferences. Results from this trial are expected to inform evidence-based practices regarding perioperative lidocaine infusion and its potential contributions to enhanced postoperative recovery in surgical patients. TRIAL REGISTRATION NUMBER: NCT07224711.

Humans↗

PubMed2026

Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages.

Genetic testing for cancer susceptibility underpins precision cancer prevention and care. Gaps in the healthcare providers' genetic literacy and an ambiguous lexicon for variant description may hinder proper delivery and clinical application of consistently trustworthy test results. The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) international consortium supports controlled terminology and recommends a framework for reporting germline variants in cancer susceptibility genes, using breast cancer as an exemplar. Moving forward towards terminological coherence across disciplines and borders, the ENIGMA Clinical Working Group launched a multinational effort to release consortium-approved translations of the published recommendations. The herein reported Vocabulary Translation Project offered an opportunity to reappraise and align the reference text to the recent BRCA1 and BRCA2 specifications to the American College of Medical Genetics and Genomics/Association for Molecular Pathology rules by the ENIGMA Variant Curation Expert Panel and to highlight country-specific differences in breast cancer risk assessment and management. The updated recommendations and their 20 translations are now provided as easy to handle documents, covering 11 of the most widely spoken languages in the world. They will contribute to minimised erroneous inferences, more informed decision-making, improved health outcomes and equity in the use of genetic testing for cancer predisposition and in translational oncology.

Humans↗

PubMed2026

Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity.

Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.

artificial intelligence↗

PubMed2026

An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy.

BACKGROUND: Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource evaluation, the DCM gene curation expert panel reconvened in 2024-2025 to conduct a reassessment of genes in DCM. METHODS: The Clinical Genome Resource semiquantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories on the basis of strength of published evidence for a DCM phenotype. Previously curated genes were reassessed, and newly reported gene-disease-mode of inheritance (MOI) relationships, termed "curations," were evaluated. RESULTS: Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence: BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, and RPL3L. Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five reevaluated genes from 2019-2020 had clinically significant changes in classification. Except for JPH2, for which curation was modified to separate autosomal dominant and AR MOI curations, clinically significant changes involved upgrades from low- to high-evidence categories (PLEKHM2, PRDM16, TBX20, TNNI3K), demonstrating the robustness of the Clinical Genome Resource gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including 6 newly evaluated genes and 1 new MOI for a previously evaluated gene, MYBPC3-AR; 4 were classified as No Known Disease Relationship, and remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs: JPH2 (AD-Strong, AR-Limited), LDB3 (AD-Limited, AR-Strong), MYBPC3 (AD-Limited, AR-Limited), and TNNI3 (AD- and AR- Strong). CONCLUSIONS: With substantial new evidence, the genetic architecture of DCM has rapidly expanded. This updated assessment of genes reported in DCM yielded 35 high-evidence curations, an increase from 19 only 5 years ago. The results of this evidence-based evaluation process inform clinical interpretation of genetic information in the care of DCM patients and families.

dilated cardiomyopathy↗

PubMed2025

Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. METHODS: This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. CONCLUSIONS: The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.

Aged↗

PubMed2026

Mitomycin C in the Endoscopic Treatment of Airway Stenosis: A Systematic Review and a Meta-Analysis.

OBJECTIVE: To assess the efficacy of adjuvant MMC in the endoscopic treatment of airway stenoses. DATA SOURCES: PubMed/MEDLINE, Cochrane Library, Scopus, Embase, and Google Scholar databases. REVIEW METHODS: A literature search was conducted following PRISMA guidelines. The PICOS tool was used to determine the eligibility criteria for this study. A single arm meta-analysis was performed for stenosis resolution, the rate of patients requiring multiple endoscopic procedures, and the rate of patients requiring other surgical treatments. RESULTS: A total number of 358 patients (median age: 48.0 years; 95% CI 44.8-50.8) were included. The median follow-up was 25.2 months (n = 244/358; 95% CI 15.4-38.3). Overall, the cumulative stenosis resolution rate was 76.37% (n = 187/254; 95% CI 59.72-89.64), the rate of patients requiring multiple endoscopic procedures was 52.33% (n = 131/260; 95% CI 32.03-72.25), and the rate of patients requiring other surgical treatments was 4.08% (n = 26/310; 95% CI 0.37-11.48). The median intervention-free interval was 366 days (n = 155/358; 95% CI 270-696). CONCLUSIONS: Current evidence does not allow definitive conclusions regarding the efficacy of adjuvant MMC in reducing recurrence or prolonging intervention-free intervals in airway stenosis. Further well-designed prospective studies are needed to clarify the role of MMC and to inform evidence-based guidelines for patient selection and treatment use. LEVEL OF EVIDENCE: NA.

Humans↗

PubMed2025

Current Advances in Surgical Techniques for Secondary Cleft Palate Repair: A Systematic Review.

ObjectiveTo systematically review advances in surgical techniques for secondary cleft palate repair, emphasizing their impact on velopharyngeal function, speech outcomes, and the methodological validity of speech assessments used in published studies.DesignFollowing PRISMA 2021 guidelines, six electronic databases were searched for articles from January 2012 to February 2025 using MeSH terms related to secondary cleft palate repair, velopharyngeal insufficiency, palatoplasty, and speech outcomes. Eligible studies included clinical reports with ≥10 patients undergoing secondary repair. Data on surgical methods, outcomes, and complications were extracted and qualitatively synthesized due to heterogeneity across studies.SettingAll published clinical studies evaluating secondary cleft palate repair outcomes.Patients/ParticipantsIndividuals presenting with residual velopharyngeal insufficiency, recurrent fistula, or speech dysfunction following primary palatoplasty.Main Outcome MeasuresSpeech resonance and intelligibility, velopharyngeal closure rate, fistula recurrence, donor-site morbidity, and obstructive sleep apnea risk.ResultsFourteen studies met the inclusion criteria. Palate-based re-repair with Furlow double-opposing Z-plasty and buccal myomucosal flaps improved resonance and closure in small to moderate gaps. Pharyngeal flap and sphincter pharyngoplasty achieved satisfactory closure in larger defects but increased the risk of airway obstruction. However, most studies lacked validated speech protocols or controlled for articulatory errors and fistula effects, limiting confidence in the interpretation of outcomes.ConclusionsWhile secondary repairs often improve resonance and velopharyngeal competence, evidence remains constrained by heterogeneity and non-validated assessment methods. Future multicenter research integrating standardized, speech pathologist-verified protocols is essential to establish evidence-based algorithms for secondary cleft palate repair.

Humans↗

PubMed2026

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↗

PubMed2026

Circulating Tumor DNA in Breast Cancer: A Liquid Biopsy Revolution for Non-Invasive Genomic Profiling and Clinical Decision-Making.

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women worldwide, underscoring the need for accurate, minimally invasive biomarkers to support precision oncology. Conventional tissue biopsy remains the standard for molecular characterization but is limited by its invasiveness, inability to capture spatial and temporal tumor heterogeneity, and challenges in serial monitoring. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising liquid biopsy biomarker capable of providing real-time genomic information throughout disease progression. This narrative review examines recent advances in ctDNA biology, analytical technologies, clinical applications, current limitations, and future directions in breast cancer management. A structured literature search of PubMed/MEDLINE, Scopus, Embase, Web of Science, and Google Scholar identified relevant English-language publications from 2015 to 2026. Current evidence indicates that highly sensitive platforms, including digital PCR, BEAMing, and next-generation sequencing, can detect clinically actionable alterations in genes such as PIK3CA, ESR1, TP53, ERBB2, AKT1, and BRCA1/2. ctDNA has demonstrated particular utility in identifying minimal residual disease, monitoring therapeutic response, detecting emerging resistance mechanisms, and guiding targeted treatment selection in advanced breast cancer. However, applications in early cancer detection, population screening, and artificial intelligence-assisted clinical decision-making remain investigational. Widespread clinical implementation is constrained by low ctDNA abundance in early-stage disease, analytical variability, limited assay standardization, and cost considerations. Continued technological innovation, prospective multicenter validation, standardized testing protocols, and evidence-based clinical guidelines are essential to fully integrate ctDNA into routine precision breast cancer care.

breast cancer↗

PubMed2025

Caregiver experiences after the death of a person with dementia with Lewy bodies: A mixed-methods analysis.

BackgroundDementia with Lewy bodies (DLB) is a common degenerative dementia, but no studies investigate bereaved caregiver experiences.ObjectiveTo investigate the experiences of caregivers three months after the death of persons with DLB using a mixed-methods approach.MethodsDyads of individuals with moderate-advanced DLB and their primary informal caregivers were followed prospectively every 6 months until the person with DLB died. Caregivers completed a study visit with questionnaires and a semi-structured interview ∼3 months later. Spearman correlation coefficients and Wilcoxon rank-sum tests evaluated the relationships of post-death measures with pre-death patient and caregiver variables. Thematic analysis was used to analyze the interviews.ResultsSeventy-three caregivers completed visits (mean 3.5 months post-death). Most of the caregivers were women (82.2%) and spouses (76.7%) or adult children (17.8%). Over 40% had scores indicating risk for clinical depression. Post-death caregiver experiences (depression, quality of life, grief, resilience) correlated with pre-death caregiver experiences. Post-death experiences did not associate with patient characteristics, disease-related symptoms, or healthcare services used in the last 6 months of life. Trajectories for caregiver measures from pre- to post-death visits varied widely. Interview themes included grief and sadness, anger, guilt and regret, relief, appreciation/gratitude, and adjusting to a new normal.ConclusionsThe finding that pre-death caregiving experiences have the strongest association with post-death experiences emphasizes the critical importance of accessible and evidence-based caregiver support before and after the death of a person with DLB. Research is needed to develop interventions for current and bereaved caregivers of individuals with DLB.Trial registration informationNCT04829656 (submitted 2021-03-22).

Caregivers↗

PubMed2026

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

Animals↗

PubMed2026

Urban Design Quality and Clinical Mental Health: A Systematic Review.

ObjectivesThis systematic review synthesizes empirical evidence on core urban design dimensions that affect clinical mental health outcomes and examines how environmental exposures mediate or moderate these relationships.BackgroundUrban design has increasingly been recognized as a determinant of psychological well-being, yet a standardized framework to evaluate its mental health impact remains underdeveloped.MethodsFollowing PRISMA 2020 guidelines, we systematically reviewed 19 quantitative empirical studies published through January 2025, examining relationships between outdoor urban design features and validated clinical mental health indicators across four major databases.ResultsFindings reveal that urban design influences clinical mental health outcomes (depression, anxiety, stress, cognitive decline) through two objective spatial scales: street-level features (imageability, enclosure, human scale, complexity) and neighborhood environments (land use mix, density, green infrastructure). Environmental exposures (traffic, noise, air pollution) operate as perceptual and experiential mechanisms that mediate or moderate the mental health effects of these spatial design features.ConclusionsWe propose an integrated three-domain conceptual framework distinguishing objective spatial design scales from subjective exposure mechanisms. This framework provides evidence-based guidance for urban planners and policymakers toward creating mentally healthier urban environments.

Humans↗

PubMed2026

High connectivity and genetic diversity in the Endangered endemic white-spotted sand bass 'camotillo' (Paralabrax albomaculatus) within the Galápagos Marine Reserve.

BACKGROUND: Paralabrax albomaculatus, known as the camotillo or white-spotted sand bass, is a finfish endemic to the Galápagos Islands. An important species in the artisanal fishery, P. albomaculatus has undergone heavy population declines in recent decades, and is categorised as Endangered by the IUCN. Despite its socio-economic importance and endemic status, nothing is currently known about the population structure of the species, impeding evidence-based fisheries management. In this study, we use microsatellite markers to investigate its population structure and genetic diversity over the east, south and west of the Galápagos archipelago. RESULTS: We found evidence of high connectivity across the archipelago, with the species constituting a single population. We also found that genetic diversity was high, despite fishing pressure and recorded ongoing population declines. CONCLUSIONS: Our results suggest that P. albomaculatus should be managed as a single fishery stock across the Galápagos. As a single-population species and fishery, managers should also be aware that P. albomaculatus is inherently vulnerable to perturbation as recruitment from other populations is not possible in the event of population decline. However, high genetic diversity gives cause for cautious optimism regarding the genetic capacity for resilience of the population to novel environmental stressors. These results should aid in the implementation of a species-specific management plan for this Galápagos endemic.

Animals↗

PubMed2026

RePo index: a multidimensional framework to quantify genetic resilience in data-limited amphibian faunas.

This study explores the resilience of Chilean amphibians to environmental disturbances through an integrative approach that combines ecological, demographic, bibliometric, and molecular information. A total of 58 species distributed across 14 genera and 9 families were evaluated via the resilience potential (RePo) index, which incorporates eleven criteria grouped into five dimensions: distribution, population trends, emerging diseases, evolutionary history, and genetic records. The results revealed high ecological vulnerability: 83% of the species were classified as non resilient (45% with no resilience and 38% with low resilience), and none reached the high-resilience category. At the family level, Telmatobiidae presented the lowest resilience values, whereas Leptodactylidae presented the highest. At the genus level, Insuetophrynus was identified as the most vulnerable taxon, with no molecular records and an extremely restricted distribution. In contrast, species such as Rhinella spinulosa and Pleurodema thaul presented moderate resilience, suggesting greater adaptive potential and relevance for functional studies. From a bibliometric perspective, a bias toward classical research topics (distribution, physiology, and taxonomy) was detected, with limited representation of integrative approaches such as genetic conservation or climate change. The conceptual modularity in the literature was low (Q = 0.1328), indicating weak thematic differentiation and little integration of omics tools. Most species lack transcriptomic and genomic data, severely limiting the assessment of their adaptive mechanisms. In this context, the RePo index has emerged as an integrative tool useful for operationalizing concepts such as evolutionarily significant units (ESUs) and management units (MUs), which are essential for evidence-based conservation. Finally, this study highlights the need to incorporate high-throughput sequencing (HTS) technologies and to participate in international initiatives, such as the Amphibian Genomics Consortium, as a strategic path forward for advancing adaptive conservation of Chilean amphibians.

Animals↗

PubMed2026

Deimplementation of inappropriate feeding practices in early care and education: a Hybrid Type 3 cluster-randomized trial.

BACKGROUND: The science of deimplementation-reducing harmful or ineffective practices-has focused almost exclusively on clinical prescribing, with no studies conducted in community or educational settings. Early care and education (ECE) settings offer a strategic venue for shaping eating behaviors, with children consuming up to 500 meals annually in these environments. However, ECE educators routinely use feeding practices that undermine self-regulation, including pressuring children to eat, rushing mealtimes, and offering food as reward. These practices contribute to food aversions, diminished self-regulation, and obesity risk. METHODS: We will conduct a Hybrid Type 3 cluster-randomized trial evaluating a co-designed deimplementation strategy package (WISE Words) across 88 ECE sites in Arkansas and Louisiana. Sites will be randomized 1:1 to WISE Words or usual practice, with usual practice sites receiving the intervention after two years (waitlist design). WISE Words includes six strategies: dynamic training using improvisation methods, peer learning collaboratives with goal setting, external facilitation, audit and feedback, environmental reminders, and tailored educational materials. The primary outcome is de-adoption of inappropriate feeding practices measured via direct mealtime observation (Table Talk). Secondary outcomes include adoption of evidence-based practices, acceptability, appropriateness, and sustainability at 12- and 24-months post-intervention. Child outcomes include Body Mass Index, skin carotenoid levels (Veggie Meter) willingness to try new foods (observed) and food neophobia (teacher and caregiver report). An explanatory sequential mixed methods design will test mechanisms of change derived from the Implementation Trust Building Theory of Change examining whether trust mediates strategy effects on outcomes. DISCUSSION: This trial extends deimplementation science into community settings by targeting culturally embedded behavioral practices rather than clinical prescribing behaviors. Results will inform approaches to shifting entrenched practices in ECE and similar settings while testing trust as a deimplementation mechanism. Sustainability assessments will address a notable gap, as few studies have examined whether deimplementation effects persist. TRIAL REGISTRATION: NCT07101321, July 20, 2025.

Humans↗

PubMed2026

Research progress on multi-mechanism analysis and protection strategies of ovarian aging and fertility decline.

Age-related fertility decline is an increasingly important challenge in reproductive medicine, driven largely by progressive ovarian aging. The aging ovary undergoes functional deterioration characterized by reduced ovarian reserve and declining oocyte quality, ultimately limiting female reproductive lifespan. Although multiple molecular and cellular processes associated with ovarian aging have been identified, these mechanisms are often discussed independently, limiting an integrated understanding of how they interact within the ovary. In this review, we propose an ovary-centered, multi-mechanistic framework to organize current evidence on ovarian aging and fertility decline. We discuss how genomic instability, telomere attrition, mitochondrial dysfunction, oxidative stress, chronic cellular stress responses, and alterations in ovarian signaling and microenvironmental homeostasis collectively contribute to follicle depletion and impaired oocyte competence. Particular emphasis is placed on signaling pathways involved in follicle activation and stress adaptation, including PI3K/AKT/mTOR, FOXO3, Hippo, and AMPK-Sirtuin networks, while acknowledging that many mechanistic relationships remain incompletely defined in physiological ovarian aging. Building on this integrative perspective, we further evaluate mechanism-oriented intervention strategies, including mitigation of cellular stress, metabolic and signaling modulation, optimization of the ovarian microenvironment, established fertility preservation technologies, and emerging exploratory approaches. By integrating current mechanistic and translational evidence, this review provides a conceptual framework for understanding ovarian aging and highlights future directions for evidence-based fertility preservation and reproductive health management in the context of aging.

Humans↗

PubMed2026

Large-scale benchmarking of prokaryotic annotation tools across thousands of species.

BACKGROUND: Genome annotation is an important step in deriving functional meaning from prokaryotic sequencing data, yet systematic evaluations guiding tool selection are lacking. We present the first large-scale investigation of four prominent open-source annotation tools (Prokka, Bakta, EggNOG-mapper, and PGAP) across 156,033 diverse genomes. This includes Escherichia coli strains for baseline performance, thousands of archaea and bacteria genomes, as well as frameshifted and metagenome-assembled genomes. RESULTS: Bakta excels in annotating high-quality bacterial genomes, while PGAP was better for archaeal genomes and challenging bacterial assemblies, including metagenome-assembled, fragmented, or contaminated samples. For Gene Ontology annotation, PGAP consistently provides broader term coverage, whereas EggNOG-mapper offers more terms per feature. CONCLUSIONS: Our findings highlight tool-specific strengths crucial for selecting optimal solutions based on genome quality, taxonomy, and origin (e.g. MAGs). This study provides an evidence-based guide for users and informs future tool development.

Molecular Sequence Annotation↗