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PubMed2026

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

Humans↗

PubMed2026

Identification of CD55 as a downstream factor of EP4 receptor signaling in colorectal cancer cells.

Prostaglandin E2 (PGE2) signaling through the E-type prostanoid 4 (EP4) receptor has been implicated in the pathophysiology of colorectal cancer (CRC). We herein identified decay-accelerating factor, also known as CD55, as a novel CRC-associated downstream factor of the EP4 receptor. The integration of transcriptomic profiling of PGE2-stimulated HCA-7 human colon cancer cells with analyses of cancer genomic databases predicted CD55 as a potential EP4 receptor-regulated target. Inhibitor-based experiments showed the induction of CD55 after a PGE2 stimulation required the EP4 receptor and Gi protein in HCA-7 cells, whereas protein kinase A signaling was dispensable. In combination with a toxicogenomic database analysis, p38 mitogen-activated protein kinase (MAPK) was identified as the predominant effector connecting the EP4 receptor to CD55 upregulation. A single-cell RNA-seq re-analysis of human CRC tissues revealed CD55 upregulation and p38 MAPK-related gene set enrichment in epithelial cells expressing the EP4 receptor, suggesting that this induction mechanism may operate in a subset of epithelial cells in clinical specimens. Collectively, these results delineate a PGE2/EP4 receptor/Gi protein/p38 MAPK signaling axis that induces CD55 expression in HCA-7 cells and epithelial tumor cells, provide new mechanistic clues for understanding the regulation of complement regulatory molecule CD55 expression by prostaglandin signaling.

Humans↗

PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

Precision Oncology in Hepatopancreatobiliary Cancer Surgery.

Advances in technology have allowed for the characterization of tumors at the genomic, transcriptomic, and proteomic levels. There are well-established targets for biliary tract cancers, with exciting new targets emerging in pancreatic ductal adenocarcinoma and potential targets in hepatocellular carcinoma. Taken together, these data suggest an important role for molecular profiling for personalizing cancer therapy in advanced disease and need for design of novel neoadjuvant studies to leverage these novel therapeutics perioperatively in the surgical patient.

Humans↗

PubMed2026

Disentangling oscillatory and aperiodic neural activity in autism: A spectral parameterization analysis of neurofeedback intervention.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by atypical neural oscillations and heterogeneous alterations in excitation/inhibition (E/I) balance, the directionality of which varies across individuals, neural circuits, and developmental stages. While Alpha-band neurofeedback (NFB) is a promising intervention, its underlying neurophysiological mechanisms remain unclear, partly due to the conflation of periodic and aperiodic signals in traditional EEG analysis. METHODS: This randomized controlled trial recruited 40 children with ASD, assigned to either an experimental group (Alpha-training NFB) or a no-feedback group. Resting-state EEG and behavioral assessments (SRS, ABC) were collected pre- and post-intervention. We employed spectral parameterization to decompose neural activity into aperiodic (1/f slope, offset) and periodic (periodic alpha power, center frequency) components. RESULTS: NFB training yielded significant behavioral improvements in social cognition and relating skills. Physiologically, the experimental group exhibited a significant steepening of the aperiodic slope (increased exponent), reflecting a reduction in neural noise and potential optimization of inhibitory modulation. Furthermore, we observed enhanced periodic alpha power and an acceleration of the alpha center frequency (ACF), indicative of improved neural efficiency and maturation. These physiological shifts in frontal and occipital regions were significantly correlated with improvements in behavioral scores. CONCLUSION: Alpha-training NFB was associated with improvements in caregiver-rated behavioral scores and modulated spectral features of resting-state EEG in children with ASD. These findings validate the utility of spectral parameterization markers in evaluating neuromodulatory interventions.

Humans↗

PubMed2026

Skin cell suspension autograft as an evidence-based innovation in burn and wound treatment: A systematic review of global evidence across two decades.

BACKGROUND: Skin cell suspension autograft (SCSA) is a point-of-care approach to wound management facilitating epithelialization while reducing burden associated with conventional autografting. Despite growing clinical use of SCSA across diverse wound etiologies, the global clinical evidence describing its use has not yet been comprehensively synthesized. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to identify studies between January 2000 and December 2024 reporting clinical use of SCSA for wound closure. Data on patient demographics, wound characteristics, and treatment methods were extracted. Clinical, safety, and health economic outcomes were extracted for comparative studies evaluating SCSA against control treatments. RESULTS: Ninety-nine studies across 13 countries were included. Across the overall dataset, SCSA was used alone or in combination with autografting for burns, surgical wounds, traumatic injuries, inflammatory conditions, and chronic wounds. Among comparative studies (n=27), SCSA consistently reduced donor skin, and healing outcomes favored SCSA in 61%, while 39% reported equivalent outcomes. Pain and esthetic outcomes more frequently favored SCSA, while safety outcomes were generally similar, with some studies favoring comparators. Health-economic outcomes suggested potential reductions in length of stay and resource utilization, although findings were variable across studies. CONCLUSION: The available global evidence supports SCSA as a versatile modality for supporting epidermal coverage across wound types and clinical contexts. However, the findings should be interpreted in the context of the limitations of this review, which include heterogenous study designs, variable outcome reporting, predominance of non-randomized data, and the absence of a formal quantitative analysis. Nevertheless, the demonstrated clinical and economic benefits in comparative studies reinforce the role of SCSA as an evidence-based innovation for burn and wound treatment.

Humans↗

PubMed2026

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

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PubMed2026

Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin: A Randomized Controlled Trial.

BACKGROUND: Fear of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of community-acquired pneumonia (CAP) frequently leads to empiric vancomycin coverage. Data evaluating the use of MRSA polymerase chain reaction (PCR) nasal swab testing to guide vancomycin de-escalation is limited for patients in the intensive care unit (ICU). METHODS: Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin (STOP-Vanc) is a pragmatic, prospective, single-center, non-blinded randomized trial in which adult ICU patients with suspicion of CAP were randomized 1:1 to receive usual care either with (intervention) or without (control) the addition of MRSA nares PCR testing following ICU admission. The primary outcome was vancomycin-free hours alive, defined as the expected number of hours alive and free of vancomycin use within the first 7 days of trial enrollment as estimated using a longitudinal proportional odds state transition model adjusted for baseline covariates. RESULTS: A total of 277 adult ICU patients were randomized. Methicillin-resistant Staphylococcus aureus PCR nasal swab testing had a negative predictive value (NPV) of 98.9% in the intervention arm. The primary endpoint, vancomycin-free hours alive, was 105.7 in the control arm and 109.7 in the intervention arm (adjusted difference, 4 hours; 95% CI, -9.5-18.2; P = .458). CONCLUSIONS: Despite MRSA PCR nasal swab testing demonstrating a high NPV in this critically ill population, MRSA PCR nasal swab testing did not decrease the duration of vancomycin use or 30-day mortality among ICU patients with suspected CAP. Additional clinician education and antimicrobial stewardship interventions might be needed to reduce vancomycin use in this patient population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT06272994 (STOP-Vanc).

Humans↗

PubMed2026

Use of Wearable Sensors in Angelman Syndrome: A Systematic Review.

BACKGROUND: Wearable sensors are a promising method for collecting clinical trial outcome data for people with Angelman syndrome (AS). However, there has yet to be a systematic probe into the ways in which wearable sensors have been successfully used in AS. The current study aims to provide a quantitative summary of wearable sensors used in AS, including contexts of use and psychometric properties, and to present key narrative highlights. METHOD: Literature searches were performed in three electronic databases: APA PsycInfo, PubMed and Web of Science Core Collection. Data items were categorized into four categories: sample characteristics, study methodological details, wearable sensor characteristics and psychometric properties assessed. Sample characteristics included sample size, age, biological sex, race/ethnicity and cognitive/developmental functioning. Study methodological details were subdivided into study design and setting. Wearable sensor characteristics included sensor type, placement site, means of attachment, assessed construct and sensor-related data loss. Psychometric properties assessed included reliability and validity of sensor-derived data. RESULTS: We identified 16 articles through our systematic review. Wearable sensors were used to study sleep (n = 10, 62.5%), language (n = 2, 12.5%), gait (n = 2, 12.5%), caregiver proximity (n = 1, 6.3%), EEG power (n = 1, 6.3%), and arousal (n = 1, 6.3%) in AS through actigraphs, vocalization recorders, inertial sensors, radio-frequency identification watches, wireless EEG caps, and functional near-infrared spectroscopy caps, respectively. Findings from these studies broadly indicate that wearable sensors are feasible, reliable and valid for assessing a range of behaviours relevant to AS. CONCLUSIONS: Wearable sensors are a promising solution to enhance assessments in AS. However, with the small extant literature characterized by small sample sizes and restricted focus on a few relevant features in AS, there remains ample opportunities to explore the use of wearable sensors in people with AS. Additional studies will better inform clinical decision-making and ultimately improve the lives of people with AS and their families.

Humans↗

PubMed2026

Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32.

BACKGROUND: Circulating levels of cancer antigen (CA) 15-3 have been associated with distant breast cancer recurrence; data on breast cancer subtypes are sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined breast cancer subtypes in MA.32. METHODS: A total of 3649 participants with T1-3, N0-1, M0 breast cancer were randomly assigned; 2740 (75.1%) provided blood at entry (mean = 278 days postdiagnosis) and 6 months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence-free survival (RFS) were examined in luminal (estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative), triple-negative (estrogen receptor, progesterone receptor, HER2 negative) and HER2-positive (any estrogen receptor, progesterone receptor) breast cancer using Cox proportional hazards models. RESULTS: Mean age was 52 years. Breast cancer was luminal in 1589 (58.7%), triple negative in 655 (24.2%), and HER2 positive in 464 (17.1%) participants. Median follow-up was 96 months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6 months was associated with poor distant RFS in luminal and triple-negative breast cancer (hazard ratio [HR] per 25% increase = 1.41, P < .0001, and HR = 1.35, P < .0001, respectively). New elevations in CA 15-3 at 6 months were adversely associated with distant RFS in those with luminal or triple-negative breast cancer (HR = 4.14, 95% CI = 2.69 to 6.38; P < .001; and HR = 3.57, 95% CI = 1.59 to 7.99; P = .002, respectively). In HER2-positive breast cancer, CA15-3 was not associated with distant RFS. CONCLUSION: Rising CA 15-3 was associated with reduced distant RFS in luminal and triple-negative breast cancer but not in HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01101438.

Humans↗

PubMed2026

Pharmacogenomics of antipsychotic-induced weight gain: A systematic review.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a major clinical concern, affecting approximately 30% of patients. Clinical predictors explain only part of AIWG risk. Genetic and molecular variations are hypothesized to contribute to susceptibility. The purpose of this review is to summarize recent results to identify replicated and novel findings. STUDY DESIGN: Applying PRISMA guidelines, we searched MEDLINE, Embase, and PsycINFO (May 2018-May 2026) for studies on genetic and molecular associations with AIWG, extending our prior review. Reviews, editorials, and conference abstracts were excluded. We extracted study characteristics (design, diagnosis, antipsychotic exposure, sample size, ancestry, genetic variants, and AIWG outcomes) (e.g., ≥7% weight gain, BMI change). RESULTS: Fifty-three studies met inclusion criteria. In candidate gene studies, the most consistently replicated genes associated with AIWG were observed for DRD2, HTR2C, and MC4R. Multiple novel associations were identified by genome-wide association studies (GWAS) (e.g., MAP2K1, ZDBF2, PEPD), polygenic risk scores (PRS) (e.g., body mass index PRS), gene expression (e.g., CYP3A4, EP300), and epigenetic analyses (e.g., cg12034943 at CRTC1). CONCLUSIONS: Polymorphisms in candidate genes related to neurotransmission and appetite regulation continue to be investigated for associations with AIWG, while novel findings have emerged from GWAS, gene expression, and epigenetic studies. Evidence remains inconsistent due to limited replication, methodological variability, sparse ancestry data, and geographical underrepresentation. No single genetic variant is ready for clinical use, and multi-omic and multi-ancestry models are needed to improve prediction and clinical utility.

Humans↗

PubMed2026

Patient and hospital factors associated with disparities in acute stroke treatment in community and academic hospitals.

BACKGROUND: Systemic barriers may affect identification, emergency transportation (EMS), and care coordination for people with stroke. We assessed patient- and hospital-level factors for associations with pre-hospital and emergency department care. We compared trends for patients presenting to an academic medical center (AMC) versus community hospitals (CHs). METHODS: We conducted a retrospective cohort study at an AMC (Tufts Medical Center) with 542 patients aged ≥18 years hospitalized with acute ischemic stroke or transient ischemic attack between 1/1/2018-12/31/2020 who presented directly to AMC or presented to AMC as a transfer from initial contact CHs. Primary outcomes were EMS use, stroke code activation, door-to-CT time, and door-to-needle time. RESULTS: AMC patients identifying as non-Hispanic Asian (odds ratio (OR) = 0.25; 95% confidence interval (CI) = 0.13-0.47) and Hispanic (OR = 0.19; 95% CI = 0.05-0.72) and CH non-Hispanic Black/African-American patients (OR = 0.17; 95% CI = 0.05-0.62) were less likely to use EMS compared to non-Hispanic white patients. Patients with non-English primary language were less likely to use EMS (OR = 0.38; 95% CI = 0.23-0.63) compared to English-speaking patients in both hospital settings. CH Hispanic patients were less likely to have stroke code activation (OR = 0.24; 95% CI = 0.05-0.86) compared to non-Hispanic white patients. CH patients were less likely to have stroke code activation (OR = 0.12; 95% CI = 0.07-0.19), had 31% shorter door-to-CT time (95% CI = 15-43% shorter), and had 29% longer door-to-needle time (95% CI = 5-58% longer). CONCLUSION: Patient-level factors and hospital setting were associated with differences in acute care suggesting opportunities for community outreach on EMS use, interventions to alleviate language barriers, and a need to address systemic biases.

Humans↗

PubMed2026

Diversity and population connectivity of members of the family Eunicidae inhabiting deep-water corals in the North Atlantic.

Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic and genomic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230 m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Leodice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000 km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.

Animals↗

PubMed2026

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals↗

PubMed2026

Treatment of OSA using mandibular advancement versus CPAP in improving cardiovascular health.

BACKGROUND: Obstructive sleep apnea is a significant risk factor for hypertension. We assessed the relative effectiveness of mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) in reducing 24 h ambulatory blood pressure (BP) and other health-related outcomes over 12 months. METHODS: In a randomized, non-inferiority trial, 321 participants with hypertension and increased cardiovascular risk were recruited for polysomnography. Of these, 220 with moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥15 events/hour) were randomized to MAD or CPAP (1:1). We report the final outcomes at the 12-month follow-up. RESULTS: A total of 180 participants (MAD: 89; CPAP: 91) completed the 12-month follow-up. Median usage for MAD and CPAP was 5.5 and 4.9 h per night, respectively. Compared to baseline, the 24 h mean arterial BP at 12 months decreased by 2.3 mmHg (P = 0.200) in the MAD group and by 1.0 mmHg (P = 0.999) in the CPAP group. The difference between-groups was -0.6 mmHg (95% confidence interval: -2.53 to 1.39, non-inferiority P < 0.019). The MAD group demonstrated a larger reduction in asleep BP compared to the CPAP group. The prevalence of excessive daytime sleepiness in the MAD group decreased from 30.3% at baseline to 10.1% at 12-month follow-up (P = 0.001), and from 38.5% to 7.7% in the CPAP group (P < 0.001). The between-group difference was 10.6% (P = 0.097). No significant within-group or between-group differences were observed in the prevalence of arrhythmias and plasma levels of cardiac biomarkers. CONCLUSION: At 12-month, MAD is non-inferior to CPAP for reducing 24 h mean arterial BP in participants with hypertension and increased cardiovascular risk. TRIAL REGISTRATION: NCT04119999.

Humans↗

PubMed2026

Exercise Snacks Are Feasible to Perform in the Real World and Improve Physical Capacity for Adults Living With Non-Insulin Treated Type 2 Diabetes: A Randomised Trial.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N = 69; 46 females; mean age ± SD: 58 ± 11 years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4 × 1-min bouts of either vigorous or low intensity exercise, respectively, on ≥ 5 days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A1c (HbA1c), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p = 0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p = 0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p < 0.001), there were no between-group differences in the change in any secondary outcome (all p > 0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p = 0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

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PubMed2026

Pharmacokinetic and Pharmacodynamic Bio-Similarity of ADL-018 to Innovator Omalizumab: A Randomized Study in Healthy Adults.

Bioequivalence and safety of ADL-018, an omalizumab biosimilar, were compared with United States-licensed omalizumab (US-OMA) and European Union-approved omalizumab (EU-OMA), both approved for allergies. Healthy adults were randomized (1:1:1) to receive a dose of ADL-018, US-OMA, or EU-OMA (150 mg/mL). Pharmacokinetic (PK) parameters, including AUC(0-last), AUC(0-∞), and Cmax, were considered equivalent if 90% CIs of geometric mean ratios (GMRs) were within predefined equivalence margin (0.80-1.25) using ANCOVA model. Other PK parameters, pharmacodynamics (PD) (free/total immunoglobulin E [IgE]), immunogenicity, and safety were compared. Overall, 306 participants (n = 102 per arm) were dosed; 287 completed the study. Equivalence of primary PK parameters was confirmed for pairwise comparisons, with 90% CIs within the predefined margin (GMRs of ADL-018 vs US-OMA: AUC(0-last)-1.08, AUC(0-∞)-1.07, Cmax-1.05; GMRs of ADL-018 vs EU-OMA: AUC(0-last)-1.06, AUC(0-∞)-1.06, Cmax - 1.05; and GMRs of US-OMA vs EU-OMA: AUC(0-last)-0.99, AUC(0-∞)-0.99, Cmax-1.00). PK/PD parameters were comparable across arms. Increase in total IgE (AUEC ∼30,000 to 35,000 h IU/mL) and decrease in free IgE (AUEC ∼29,000 to 35,000 h IU/mL) were comparable across arms. Similar incidence of adverse events across arms (treatment-emergent adverse events: ADL-018, n = 6; US-OMA, n = 5; EU-OMA, n = 4) was observed. ADL-018 demonstrated PK/PD equivalence and comparable safety profile to reference omalizumab.

Humans↗