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PubMed2026

Definition and prevalence of residual disease in inflammatory arthritis: a systematic literature review and meta-analysis.

OBJECTIVE: To assess how residual disease (i.e., clinically relevant signs/symptoms despite achieving treatment targets) is defined in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), and estimate the prevalence/severity of residual disease in these diseases. METHODS: Systematic review of original research in RA/PsA/axSpA. Two key residual disease components were extracted: (1) the patient's disease state (often remission/low disease activity) and (2) which residual signs/symptoms were measured, e.g. swollen joints or fatigue (indicators of residual disease). Frequencies of the disease states and indicators were described (Objective 1). Prevalence (%) and severity (absolute score on instrument, e.g. fatigue NRS) of residual disease was analysed by indicator, using random effects meta-analysis (≥4 studies) or descriptively (<4 studies) (Objective 2). RESULTS: Regarding residual disease definitions (59 studies), disease states were almost exclusively disease activity-based (>99%), but with much variation in specific instruments/thresholds. Across diseases, physician-reported (66%) and patient-reported (73%) indicators were used more often than laboratory indicators to define residual disease (46%). Especially peripheral joint counts, pain, physical function and CRP were frequently used (42-56% of studies). The prevalence of residual disease (84 studies) was notable. For example, 5-25% of RA and PsA patients in remission still had swollen joints, and up to one-third reported relevant pain or fatigue. For axSpA, evidence was limited. CONCLUSION: Residual disease definitions in RA/PsA/axSpA are based on various disease activity instruments/thresholds and indicators (signs/symptoms). Residual disease affects up to half of patients. Future research should aim for a consensus-based definition of residual disease.

Humans↗

PubMed2026

No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.

INTRODUCTION: Hip osteoarthritis (OA) is estimated to affect 62.6 million individuals by 2050. A probable link exists between alcohol use and hip OA. However, the results are inconsistent, and the relationship between alcohol and hip OA remains speculative. To address these gaps, this study aimed to utilize the diverse, nationally representative All of Us Research Program dataset to explore the association between alcohol consumption and hip OA. METHODS: This retrospective case-control study utilized data from the All of Us Research Program Controlled Tier Dataset v8. 17,517 hip OA cases and 70,068 controls were identified. A 1:4 case-to-control matching ratio was applied based on age and sex. Alcohol use frequency was categorized into five levels: Never, Monthly or Less, Two to Four Times per Month, Two to Three Times per Week, and Four or More Times per Week. Multivariable logistic regression models evaluated the association between alcohol use frequency and hip OA after adjusting for demographic and clinical variables. RESULTS: Multivariable analysis found that alcohol use frequency was not significantly associated with hip OA. Compared to never users, participants with low (OR 0.98, 95% CI 0.93-1.04, P = 0.583), moderate (OR 0.99-1.01, all P > 0.05), and high (OR 1.02, 95% CI 0.95-1.09, P = 0.599) levels of alcohol consumption had no statistically significant differences in odds of hip OA. Female sex, Asian race, diabetes, hypertension, hyperlipidemia, and nicotine dependence increased the odds of hip OA. CONCLUSION: Any level of alcohol consumption was not significantly associated with the odds of hip OA. This study adds valuable insight to the current body of conflicting evidence. Further prospective studies appear warranted to shed light on the long-term effects of different alcoholic beverages on different joints. Key Points • This study found no significant association between any degree of alcohol consumption and the odds of developing hip osteoarthritis. • Utilizing data from 87,585 adults in the NIH "All of Us" Research Program, this is the first study to analyze this relationship in a large, nationally representative population. • The research provides clarity to previously conflicting literature by demonstrating that alcohol lacks a clear harmful or protective effect on the clinical course of the disease. • The analysis highlights that independent risk factors such as Asian race, nicotine dependence, and components of metabolic syndrome increase the odds of hip osteoarthritis.

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

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗

PubMed2026

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40 min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult↗

PubMed2026

The effect of drysuit diving in warm water on body temperature and post immersion orthostatic hypotension.

INTRODUCTION: Warm-water diving can limit heat dissipation, particularly when performed in fully encapsulating protective gear, leading to substantial thermal and cardiovascular strain that may impair diver safety. Following immersion, removal of hydrostatic support combined with heat-induced vasodilation may reduce central blood volume and increase susceptibility to orthostatic intolerance during egress and recovery. The extent to which this thermal strain impairs post-immersion orthostatic tolerance remains unknown. METHODS: Four randomised, crossover immersion trials were conducted at 28°C, 33°C, 38°C without precooling (38°C), and 38°C with precooling (38°C + Cool), with subjects wearing fully encapsulating dive gear. Subjects walked for up to 60 minutes at approximately 50% of O2max heart rate (HR) or until core temperature (Tc) reached 38.5°C, or they voluntarily stopped. Tc, HR, and perceptual measures were recorded every 10 minutes. Orthostatic tolerance was assessed after immersion via a 70° head-up tilt test. RESULTS: Eight healthy adults completed all aspects of the study. Tc and HR were higher during both 38°C conditions compared with 28°C and 33°C (all P < 0.01) with no differences between 38°C and 38°C + Cool. Sweat loss exceeded 1.2 (SD 0.67) L⋅h-1 in both 38°C conditions compared with ≤ 0.3 (0.32) L⋅h-1 at 28°C and 33°C (P < 0.01). Survival analysis showed orthostatic tolerance decreased with increasing thermal stress (log-rank P = 0.027; trend P = 0.003). Precooling did not reduce peak Tc or HR, nor did it improve tolerance time in 38°C water. CONCLUSIONS: Encapsulated warm-water diving causes heat stress and cardiovascular strain that persists after immersion, impairing orthostatic tolerance. Precooling does not significantly reduce these outcomes.

Humans↗

PubMed2026

Multi-omic biomarkers in cardiovascular disease: Discovery to clinical translation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, necessitating improved risk stratification and early detection strategies. Multiomics approaches that integrate genomics, transcriptomics, proteomics, metabolomics, and epigenomics offer unprecedented opportunities for biomarker discovery and precision medicine in cardiovascular care. This narrative review examines the current landscape of multiomics biomarkers for CVD, tracing their evolution from discovery to clinical translation. We synthesize evidence from recent studies evaluating the clinical utility of integrated omics approaches across diverse cardiovascular conditions, including atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation. High-throughput proteomics has identified novel protein signatures that enhance cardiovascular risk prediction beyond traditional risk factors. Metabolomics has revealed pathway-specific biomarkers, including trimethylamine N-oxide and lipid species, associated with atherogenesis. Polygenic risk scores derived from genomic data demonstrate incremental value when combined with clinical risk scores. Multiomics biomarkers represent a transformative approach to cardiovascular risk assessment and disease management.

Humans↗

PubMed2026

Plasma proteomics: considerations for preanalytical variability; a systematic review with narrative synthesis.

BACKGROUND: The plasma proteome (PP) is a dynamic system subject to pathology-associated changes and a focus for novel disease biomarker discovery. Disease-related PP research assumes protein concentrations in test specimens accurately reflect the in vivo milieu. However, measures to maintain the physicochemical integrity of the proteome before assay are often rudimentary, poorly described, or lacking standardisation in published studies. Contrastingly, in laboratory medicine, there is an expectation that errors in the so-called "preanalytical phase" (PAP) that impact patient results are understood, monitored, and mitigated against, while also being well described in research publications. There is therefore scope for good practice from laboratory medicine to inform PP research workflows. This review considers factors in the PAP which may impact the validity of PP results. CONTENT: A systematic review was conducted per PRISMA guidelines, limited to English-language peer-reviewed studies (2014-2024). Candidate studies were imported, screened, and managed using Covidence systematic review software. SUMMARY: 15 eligible studies were reviewed, covering many relevant processes. 11 studies reported statistically significant differences in PP due to factors in the PAP. Temperature and time-to-processing were the most commonly reported factors affecting the PP, with significant effects reported in 8 studies. OUTLOOK: PAP variability can significantly affect results in PP studies. Careful consideration of the effect of each stage of the PAP is needed when working with the PP. In multicenter studies, pre-defined and research question-specific sample processing workflows are essential for reducing PAP variability, which helps ensure the validity of PP studies.

Humans↗

PubMed2026

Recovering membrane interaction kinetics of single molecules from 3D tracking data.

Interactions between cytosolic biomolecules and the bacterial inner membrane are fundamental to many cellular processes, yet directly measuring their binding kinetics in living cells remains challenging. Conventional 2D single-molecule tracking analyses can be insufficient, particularly when membrane association does not markedly alter the diffusion rate. Here, we present a method to recover membrane interaction kinetics from 3D single-molecule trajectories in rod-shaped bacteria. Using simulated 3D tracking data, we identify membrane-associated motion by quantifying how well short trajectory segments follow the circular curvature of the cell membrane. The resulting measure is further analyzed using a hidden Markov modeling framework, enabling robust discrimination between cytosolic and membrane-bound states and capturing the dynamics of state transitions without requiring diffusion-rate changes or direct colocalization with membrane markers. This work establishes a general framework for extracting membrane interaction kinetics from 3D single-molecule tracking data in live bacteria and highlights the value of realistic microscopy simulations for quantitative interpretation and systematic bias assessment.

Kinetics↗

PubMed2026

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health↗

PubMed2026

New World screwworm: a re-emerging parasitic threat.

PURPOSE OF REVIEW: New World screwworm (NWS) is an emerging parasitic threat in Central America and Mexico, which is spreading northward into the southern United States. Here we highlight the changing epidemiology, lifecycle of the NWS fly, clinical presentation, identification, treatment, and potential complications of NWS myiasis. RECENT FINDINGS: Despite decades of successfully containing NWS flies south of the Darien Gap in southern Panama, NWS flies reemerged in the Central America region in 2023 and have continued to spread northward ever since. On 3 June 2026, United States Department of Agriculture (USDA) confirmed the identification of an NWS infestation in a young calf in southern Texas. In addition to describing the current epidemiology of the NWS outbreak, we present information about clinical presentation and management of NWS myiasis in patients and include representative cases of patients who experienced NWS myiasis. SUMMARY: This review provides important epidemiologic and clinical updates to an emerging parasitic threat so clinicians can understand the risks and clinical management for patients with suspected NWS myiasis.

Animals↗

PubMed2026

Breastfeeding Outcomes After Radiofrequency Ablation and Surgical Excision of Fibroadenomas Compared to Natural History: A Retrospective Cohort Study.

BACKGROUND: Fibroadenomas, common benign breast tumors in women of reproductive age, are increasingly managed with minimally invasive radiofrequency ablation (RFA) or surgical excision. However, their impact on breastfeeding outcomes remains underexplored. We aimed to assess breastfeeding ability and breast tissue changes in women treated with RFA or surgery compared to those with untreated fibroadenomas. METHODS: In this retrospective cohort study, we evaluated 153 women with biopsy-confirmed fibroadenomas across five groups: RFA with prior breastfeeding (RFA-PreBF; n = 26), RFA with posttreatment breastfeeding (RFA-PostBF; n = 22), surgical excision with prior breastfeeding (Surgical-PreBF; n = 30), surgical excision with posttreatment breastfeeding (Surgical-PostBF; n = 20), and noninterventional with breastfeeding (Observation-BF; n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months, and all breastfeeding attempts occurred at a minimum of 12 months postprocedure. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1). FINDINGS: The combined RFA group (n = 48) had a higher complete lactation failure rate (14.6%) than the Observation-BF group (3.6%; Fisher's exact test, p = 0.045). Similarly, the combined surgical group (n = 50) had a higher complete lactation failure rate (16.0%) than the Observation-BF group (p = 0.034). When pooled, the combined intervention group (n = 98) showed a complete lactation failure rate of 15.3% versus 3.6% in the Observation-BF group. Residual tissue correlated with lactation impairment in the RFA group (Spearman's ρ, p < 0.05). Ultrasound showed no tumor recurrence, with cystic changes in some cases not linked to breastfeeding impairment. Power analysis confirmed 80% power to detect a medium effect size (f = 0.25, Fig. 1), supporting the study's robustness.7 RFA-PreBF (n = 26), RFA-PostBF (n = 22), Surgical-PreBF (n = 30), Surgical-PostBF (n = 20), and Observation-BF (n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1).[Figure: see text]Interpretation:RFA and surgical excision are effective for fibroadenoma management but increase the risk of complete lactation failure compared to untreated fibroadenomas. Careful patient selection, precise procedural techniques, and vigilant posttreatment monitoring are essential to optimize breastfeeding outcomes, particularly for women planning future pregnancies.

Humans↗

PubMed2026

PCa Detection in PI-RADS 4 and 5 Lesions: Comparison of [68Ga]Ga-PSMA-11 PET/CT-Guided Robot-Assisted Biopsy Versus mpMRI Cognitive-Fusion TRUS-Guided Prostate Biopsy.

Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-naïve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

Humans↗

PubMed2026

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

PubMed2026

Genomic diversity and thermal niches of Aspergillus molds disrupting rind formation of surface-ripened cheeses.

Filamentous fungi play important roles in the development of surface-ripened cheese microbial communities and contribute to the aesthetics and flavors of these products. Much is known about the diversity and ecology of desirable cheese fungi, but our understanding of the natural history of cheese spoilage molds is limited. The goal of this work was to characterize the genomic diversity of Aspergillus species contaminating artisan cheeses and to identify how the abiotic environment of cheese (the substrate itself and temperature) may constrain the growth of Aspergillus. Comparative genomics identified two main species of Aspergillus, A. westerdijkiae and A. ostianus, as the spoilage molds across three different facilities in the Northeastern United States that experienced contamination events. Multiple genomic types of A. westerdijkiae were found across the different cheese production facilities, indicating that these contamination events are not caused by a single clonal strain. All A. westerdijkiae isolates produced ochratoxin A, but concentrations varied greatly across strains. RNA-sequencing of A. westerdijkiae on nutrient-rich lab media (malt extract agar) versus cheese curd agar identified a suite of pathways enriched in expression on cheese, including degradation of amino and fatty acids. Experiments measuring growth over a range of temperatures identified that spoilage Aspergillus species have a higher optimal growth temperature compared to desirable fungal species in cheese rinds and are outcompeted by Penicillium species at temperatures lower than 15°C. Global fungal metabarcoding databases suggest that A. westerdijkiae is not normally found in natural habitats of the Northeastern United States, and it may be introduced to this region.IMPORTANCEOver the past decade, disruptive contamination events of Aspergillus spoilage molds have occurred at cheese production facilities in Massachusetts, Connecticut, and Vermont in the United States, causing aesthetic, flavor, and potential safety issues. Our work highlights independent introductions of different strains of A. westerdijkiae into multiple cheese facilities and suggests that temperature could be used to control the abundance of Aspergillus spoilage molds. Based on our analysis of the global distribution of A. westerdijkiae, it is not invading cheese facilities from local fungal populations and may be a contaminant in materials used for cheese production.

Aspergillus↗

PubMed2026

Maternal anemia and the risk of preterm birth: a meta-analysis.

BACKGROUND: Globally, preterm birth continues to be a primary contributor to neonatal complications and fatalities. Anemia among the most common nutritional disorders in pregnancy has been proposed as a potential contributor to early delivery. Although extensively studied, the available evidence does not yet provide a clear consensus. This study aimed to conduct a meta-analysis to quantitatively assess the relationship between maternal anemia and the risk of preterm birth. METHODS: This meta-analysis was conducted and reported in accordance with the PRISMA guidelines and the MOOSE checklist. A systematic and exhaustive search was performed across multiple electronic databases PubMed, Scopus, Web of Science, Embase, and the Cochrane Library to identify relevant studies published from inception to 1 January 2025. Effect sizes were combined using a random-effects meta-analysis. RESULTS: A total of 45 articles, reporting 60 independent study populations comprising 2,119,392 pregnant individuals were included. Considerable heterogeneity was found across the included studies (I2 = 95.54%, p < 0.001), which justified the application of a random-effects model for pooling effect sizes. Maternal anemia was significantly associated with an increased risk of preterm birth (pooled odds ratio[OR] = 1.28, 95% confidence interval [CI]: 1.20-1.36, p < 0.001). Despite substantial heterogeneity, sensitivity analyses confirmed the robustness of this association. The relationship was strongest in studies conducted in Asia (OR = 1.30, 95% CI: 1.22-1.40; p < 0.001) and the Europe (OR = 1.24, 95% CI: 1.08-1.41; p = 0.001) and reached statistical significance when anemia was assessed during the first trimester (OR = 1.12, 95% CI: 1.03-1.51; p = 0.007) and the third trimester (OR = 1.65, 95% CI: 1.42-1.91; p < 0.001), while no significant associations were found in the second trimesters (OR = 1.10, 95% CI: 0.99-1.22; p = 0.05). Funnel plot asymmetry and a significant Egger's test (p = 0.001) indicated potential publication bias, although Begg's test was not significant (p = 0.425). CONCLUSIONS: The current evidence suggests that maternal anemia, particularly in the third trimester, is significantly associated with an increased risk of preterm birth. These findings emphasize the clinical imperative for comprehensive and timely anemia screening during the third trimester. Integrating targeted interventions such as iron and micronutrient supplementation, is essential to mitigate the risk of preterm delivery and improve neonatal outcomes.

Humans↗

PubMed2026

Clinical applications of digital twin technology in In Vitro Fertilisation.

BACKGROUND: Digital twin technology, originating from aerospace and manufacturing industries, has emerged as a transformative tool in healthcare. In vitro fertilisation (IVF) faces persistent challenges including suboptimal embryo selection, unpredictable treatment outcomes, and limited personalisation of protocols. Despite advances in assisted reproductive technology, existing literature exhibits fragmentation: artificial intelligence applications in embryo selection, ovarian stimulation, and endometrial assessment have been developed independently without systematic integration into comprehensive treatment frameworks. Digital twin technology offers unprecedented opportunities to create virtual replicas of biological systems, enabling real-time monitoring, predictive modelling, and personalised treatment strategies. AIM: This narrative review aims to critically examine the current applications of digital twin technology in IVF, evaluate its potential benefits and limitations, synthesize existing evidence into an integrative conceptual model, and identify future directions for implementation in reproductive medicine. METHOD: A comprehensive narrative review was conducted using PubMed, Scopus, Web of Science, and IEEE Xplore databases. A narrative review approach was selected over systematic review to accommodate the heterogeneity of evidence types in this emerging field, including theoretical frameworks, simulation studies, and proof-of-concept implementations that would be excluded from systematic reviews. Search terms included "digital twin," "IVF," "in vitro fertilisation," "assisted reproductive technology," "embryo selection," and "predictive modelling." Studies published between 2015 and 2025 were included, focusing on original research articles, systematic reviews, and proof-of-concept studies describing digital twin applications in reproductive medicine. RESULTS: Digital twin technology in IVF demonstrates significant potential across multiple domains including embryo development simulation, ovarian response prediction, endometrial receptivity modelling, and personalised stimulation protocols. Current applications integrate artificial intelligence, machine learning algorithms, time-lapse imaging, and omics data to create comprehensive virtual models. Early evidence suggests improvements in embryo selection accuracy, ovarian response prediction, and treatment protocol optimization, though large-scale randomized controlled trials remain limited. Implementation challenges include data integration complexity, computational requirements, regulatory considerations, and validation requirements. CONCLUSION: Digital twin technology represents a paradigm shift in IVF practice, offering personalised, predictive, and precision medicine approaches. This review synthesizes existing evidence to propose an integrative conceptual model for digital twin implementation across the IVF treatment spectrum, identifies critical knowledge gaps, and establishes research priorities to advance clinical translation. Despite current limitations, continued advancement promises improved success rates and patient outcomes.

Humans↗

PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗