Pregnancy loss remains a significant challenge in obstetric care, with traditional risk assessment methods, such as clinical history and radiological investigations, often lacking precision in predicting outcomes. This study applied machine learning (ML) to develop a robust model for identifying factors associated with pregnancy loss, with the goal of highlighting candidate predictors for further investigation and validation in future studies in African populations.

The study utilized sociodemographic, clinical and laboratory variables collected at baseline from an ongoing cohort study titled "Future maternal cardiovascular health after pre-eclampsia in an indigenous African population". A total of 1,017 pregnant women attending Mulago National Referral Hospital in Kampala, Uganda were enrolled between 2019 and 2021. However, the outcome question was not administered to women on their first pregnancy, limiting the modeling population to multigravid women (n = 655). Advanced ML tools in R and Python were employed to process the de-identified data, including rigorous data cleaning, feature selection, and handling of missing values. Several ML classifiers were trained and evaluated using cross-validation techniques and the training-test split approach, with performance assessed using Matthew's Correlation Coefficient (MCC), precision, recall and F1 score.

Random Forest achieved the highest discrimination (MCC 0.36, 95% CI 0.25-0.47; ROC-AUC 0.74, 95% CI 0.63-0.83), followed closely by CatBoost (MCC 0.35, 95% CI 0.18-0.46; ROC-AUC 0.71, 95% CI 0.61-0.77); confidence intervals for the two ensemble models overlapped substantially. Both outperformed logistic regression (MCC 0.22, 95% CI 0.08-0.35). Across both tree-based models and both SHAP and permutation-based importance methods, the number of pregnancies carried past seven months, maternal age, and maternal education ranked as the leading correlates. Subgroup analysis showed broadly consistent discrimination across reliable age, education, and maternal tribe.

A few sociodemographic and obstetric history factors are statistically associated with a documented history of pregnancy loss among multigravid women in this Ugandan cohort. Because the outcome reflects reproductive history rather than the result of an observed pregnancy, these findings should be read as hypothesis-generating groundwork for future prospective, externally validated risk-prediction research rather than as a clinical tool for identifying women at risk of a future miscarriage.

Poststroke dysphagia (PSD) is a common, debilitating consequence of stroke that affects up to 50% of patients and leads to multiple medical complications. Transcranial direct current stimulation (tDCS) therapeutic efficacy depends on the electrode montage and interindividual anatomical differences. The use of the standard C5/C6 placement based on 10-20 electroencephalography (EEG) coordinates to guide electrode placements may result in misalignment with the target position.

To investigate whether computational modeling leads to improved electric field (EF) parameters compared with those generated with standard electrode placement methods, and whether smaller sized electrodes can yield more focal results, we compared EF values across three tDCS montages targeting the cortical swallowing area (CSA): (i) optimized circular (Opt-C, 1.5 cm radius), (ii) EEG-based, conventional circular (Conv-C, 1.5 cm radius), and (iii) conventional square (Conv-S, 5 × 5 cm) electrode montages.

Structural MRI data from 50 PSD patients were analyzed. EF distributions were simulated using finite element method (FEM) analysis based on three-dimensional tetrahedral head models generated with the tES LAB 4.0 platform. Across montages, we compared EF strength, defined as the mean L2 norm of the EF (E_norm) across nodes within the target ROI, and target-specific focality, defined as the summed volume of target-ROI elements with E_norm values at or above the 75th percentile of the corresponding whole-brain gray and white matter E_norm distribution.

Significant differences in EF strength (p < 0.001) and target-specific focality (p < 0.001) were identified across the three tDCS montages. The Opt-C montage produced the highest EF strength (median: 0.3525 V/m; IQR: 0.306-0.455) and target-specific focality (median: 104.69 mm³; IQR: 88.17-120.31). Additionally, small circular electrodes resulted in significantly greater EF strength and target-specific focality than square electrodes (p < 0.001).

MRI-guided personalized tDCS planning improved modeled EF delivery to the cortical swallowing target and revealed significant deviations from conventional C5/C6 placement in patients with severe PSD. These findings support image-guided target engagement as a framework for precision neuromodulation in PSD, while prospective physiological and clinical validation is required before therapeutic efficacy can be inferred.

Mitochondrial dysfunction is increasingly recognized as a driver of maladaptive macrophage polarization in atherosclerosis (AS), but the mitochondrial genes that shape disease-relevant macrophage states remain poorly defined.

We integrated weighted gene co-expression network analysis (WGCNA), machine learning, two-sample Mendelian randomization (two-sample MR), bulk transcriptomics, single-cell analysis, disease-level validation, single-cell mediation, and in vitro perturbation to identify macrophage-relevant mitochondrial regulators in AS.

Eight candidate genes were consistently prioritized by WGCNA and machine learning; among them, microsomal glutathione S-transferase 3 (MGST3) showed the strongest protective genetic signal. Two-sample MR supported a protective association between genetically predicted MGST3 expression and coronary artery disease/coronary heart disease risk (training set OR = 0.989, 95% CI 0.978-0.999, P = 0.042; test set OR = 0.977, 95% CI 0.960-0.995, P = 0.013). Human carotid plaque validation confirmed reduced MGST3 at both mRNA and protein levels in AS lesions. Notably, despite this whole-plaque downregulation, single-cell and disease-level analyses revealed an expanded MGST3-high M2-like macrophage state in AS, suggesting a compensatory protective macrophage program within diseased plaques. MGST3-high M2-like cells displayed an OXPHOS-oriented, antioxidant, and less inflammatory transcriptional state, acted as an active signaling population, and showed higher composite MitoHealth scores. Single-cell mediation analysis further indicated that MitoHealth statistically links higher MGST3 expression to lower inflammatory activity, lower M1-like polarization, and lower atherogenic macrophage programming. In M2-polarized macrophages, MGST3 knockdown reduced M2-associated and mitochondrial/antioxidant transcripts while increasing pro-inflammatory transcripts, providing transcript-level functional support. PheWAS analysis detected no significant phenotype associations at the predefined threshold.

These findings define MGST3 as a marker of a mitochondrial-health-associated M2-like macrophage state that appears expanded within AS plaques despite reduced whole-plaque MGST3 expression. The MGST3-MitoHealth axis may represent a compensatory macrophage program linked to mitochondrial preservation and lower pro-atherogenic activation, warranting further diagnostic and therapeutic investigation in AS.

Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 receptor agonists, have transformed obesity treatment by producing substantial weight loss and improving cardiometabolic outcomes. However, their therapeutic effects are accompanied by nutritional challenges, including reduced energy intake, gastrointestinal adverse effects, loss of lean mass or fat-free mass, and the risk of inadequate protein and micronutrient intake. This scientific statement of the Polish Society of Dietetics (PTD) summarizes current evidence and provides clinical guidance on nutritional care during incretin-based therapy for obesity. The statements were developed through multidisciplinary expert synthesis and consensus; direct nutrition-specific evidence remains limited, and no formal evidence-grading system was applied. The main features of evidence-informed nutritional care during incretin-based therapy include: 1) structured baseline nutritional assessment and ongoing monitoring of dietary intake, appetite, gastrointestinal tolerance, and body composition; 2) early identification of nutritional risk, including inadequate protein intake, micronutrient insufficiency, dehydration, and excessive loss of lean mass or fat-free mass; 3) individualized dietary strategies supporting adequate nutrient intake and treatment tolerance; 4) preservation of lean mass and muscle function through appropriate protein intake and regular resistance exercise; 5) use of Mediterranean, Dietary Approaches to Stop Hypertension (DASH), or appropriately planned plant-based dietary patterns adapted to individual clinical needs; 6) targeted rather than routine nutritional supplementation based on documented deficiency or increased clinical risk; and 7) integration of registered dietitians within multidisciplinary obesity care pathways. Future research should evaluate the effects of structured dietitian-led interventions on body composition, nutritional status, treatment adherence, and long-term clinical outcomes during incretin-based therapy.

BackgroundCovert brain infarction (CBI) is a frequent incidental neuroradiological finding increasingly recognized as clinically relevant due to its association with stroke, cognitive decline, and other adverse outcomes. However, substantial uncertainty remains regarding its optimal assessment and management, and existing guidelines provide limited and heterogeneous recommendations. We aimed to develop an international expert consensus on the evaluation and management of CBI using a modified Delphi methodology.MethodsA modified Delphi process was conducted with an international, multidisciplinary panel of 21 experts from 15 countries, including neurologists, neuroradiologists, neuroepidemiologists, and geriatricians. An initial questionnaire was developed from a structured literature review and identified clinical practice gaps. The survey included 91 statements across four domains: (1) prognosis, etiology, and screening; (2) neuroimaging-based management and follow-up; (3) cardiac evaluation; and (4) pharmacological management. Two iterative rounds were conducted, with anonymized responses, controlled feedback, and structured discussion. A five-point Likert scale was used. Consensus was defined a priori as ≥70% agreement.ResultsConsensus was reached on 33/91 statements (36.3%), moderate agreement on 43/91 (47.2%), and no consensus on 15/91 (16.5%). The panel agreed that CBI is associated with increased risk of ischemic stroke, cognitive impairment, and dementia, and that risk is higher with multiple lesions. Consensus supported targeted clinical evaluation, including a cardiac workup with transthoracic echocardiography in all patients and vascular imaging in selected cases. Routine population screening and systematic post-procedural imaging were not supported. Regarding management, consensus favored optimizing vascular risk factors, particularly strict blood pressure control in hypertensive patients. There was no consensus on routine antiplatelet therapy for incidental CBI, and anticoagulation was generally not supported in the absence of cardioembolic indications. Lipid-lowering showed limited consensus regarding specific benefits for CBI-related outcomes.ConclusionThis Delphi consensus highlights substantial variability in the perceived management of CBI and identifies areas of convergence, particularly in risk stratification and control of vascular risk factors. Key uncertainties remain regarding antithrombotic strategies, lipid-lowering therapy, and long-term surveillance. These results provide a pragmatic, expert-based framework to support clinical decision-making and further highlight the need for prospective studies and randomized trials in this rapidly evolving field.

Type 2 cardiorenal syndrome (CRS) is a complex clinical syndrome characterized by chronic kidney injury resulting from chronic cardiac dysfunction. Its underlying pathophysiological mechanisms remain incompletely understood, highlighting the urgent need for disease models that better mimic human pathology and accurately simulate the progression of cardiac-induced renal injury. Existing models possess significant limitations and often fail to adequately replicate the onset and progression observed in clinical Type 2 CRS patients. We therefore hypothesized that a double-hit approach combining left anterior descending (LAD) ligation (to induce acute myocardial infarction) with transverse aortic constriction (TAC) (to increase afterload) would produce a model that highly simulates the development and progression of clinical Type 2 CRS, characterized by heart failure and subsequent renal injury. A double-hit strategy combining LAD ligation and TAC was performed in mice to induce heart failure followed by secondary renal injury. At four post-operative time points (2 weeks, 4 weeks, 6 weeks, and 8 weeks), we assessed cardiac function, renal function, inflammatory damage, energy metabolism dysfunction, and renal/cardiac fibrosis. Proteomic analysis was additionally performed to characterize molecular changes and identify the optimal model configuration. At week 2, mice developed early-stage heart failure accompanied by mild kidney inflammation and abnormal energy metabolism. By week 4, these abnormalities progressed to marked inflammation, fibrosis, chronic heart failure, and overt kidney damage. The impairments in energy metabolism, inflammation, and fibrosis peaked at Weeks 6 and 8, leading to severe dysfunction of both the heart and kidneys. This double-hit model stably recapitulates the natural progression from chronic cardiac dysfunction to chronic kidney injury observed in Type 2 CRS. It therefore serves as a powerful and innovative research platform for in-depth exploration of the molecular mechanisms underlying Type 2 CRS, screening of potential therapeutic targets, and evaluation of novel interventional strategies.

Tranexamic acid (TXA) has been widely used in primary total knee arthroplasty (TKA) to reduce perioperative blood loss, but the pooled evidence regarding blood loss, transfusion, and deep vein thrombosis (DVT) remains to be further clarified. The purpose of this meta-analysis was to evaluate the efficacy and safety of TXA in primary TKA.

PubMed, Embase, Web of Science, the Cochrane Library, and relevant additional sources were searched to identify randomized controlled trials (RCTs) comparing TXA with a control regimen in primary unilateral TKA. The primary outcomes were blood loss, transfusion, and DVT. Continuous outcomes were pooled as mean differences (MDs) with 95% confidence intervals (CIs), and dichotomous outcomes were pooled as risk ratios (RRs) or odds ratios (ORs) with 95% CIs. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects models were applied for meta-analysis. For the blood-loss outcome, an additional robustness analysis was performed using an empirical Bayes random-effects model with Knapp-Hartung standard error adjustment to evaluate whether the result was sensitive to model assumptions, given that methodological choices in random-effects meta-analysis may influence statistical significance when substantial heterogeneity is present.

A total of 17 studies were included in the systematic review and meta-analysis. TXA was associated with significantly reduced blood loss compared with control (MD = -423.28 mL, 95% CI -536.90 to -309.66; P < 0.001), although substantial heterogeneity was observed (I² = 93.44%). Leave-one-out sensitivity analysis showed that the pooled effect remained significant after exclusion of individual studies; exclusion of one influential study reduced heterogeneity to 81.88%. The Knapp-Hartung-adjusted robustness analysis yielded a similar significant effect estimate. TXA also significantly reduced transfusion risk (RR = 0.55, 95% CI 0.45 to 0.68; P < 0.001), with no significant heterogeneity (I² = 0.0%). No significant difference was found between the TXA and control groups in the incidence of DVT (OR = 0.75, 95% CI 0.47 to 1.22; P = 0.25), and heterogeneity was low (I² = 0.0%). Funnel plot inspection suggested possible asymmetry for blood loss and transfusion; however, Egger's test was not significant for blood loss (P = 0.842), whereas significant small-study effects were detected for transfusion (P = 0.002).

The current evidence indicates that TXA in primary TKA significantly reduces blood loss and transfusion requirements with no detected increase in DVT risk in the available randomized evidence. The blood loss analysis showed substantial heterogeneity, whereas the transfusion and DVT analyses were more consistent across studies.

This review aimed to map the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on gout-related and cardiometabolic outcomes in patients with type 2 diabetes mellitus (T2DM) and gout.

A scoping review was conducted following the Joanna Briggs Institute methodology and the PRISMA-ScR checklist. Searches were performed in PubMed, EMBASE, Scopus, Web of Science, LILACS/BVS, and gray literature sources. Eligible studies included patients with T2DM and gout treated with SGLT2i, assessing outcomes such as mortality, gout flares, serum uric acid (SUA) levels, emergency care visits, and hospitalizations due to gout. The PRISMA-ScR checklist is provided in Additional file 1, and the full search strategy in Additional file 2.

Of 282 articles initially identified, 22 met the inclusion criteria. Most studies were retrospective cohort studies (n = 12) or post hoc analyses (n = 8). Only three studies evaluated patients with both T2DM and gout exclusively. The main findings included reductions in SUA levels (n = 8), incidence of gout (n = 12), gout flares (n = 8), initiation of urate-lowering therapy or colchicine (n = 8), and gout-related emergency care or hospital visits (n = 1). Reductions in all-cause (n = 5) and cardiovascular (CV) mortality (n = 4) were also reported. Across the included studies, SGLT2i were frequently associated with favorable effects on the analyzed outcomes.

SGLT2i appears to be associated with multiple favorable effects in patients with T2DM and gout, including urate-lowering effects, reduced gout flares, and lower mortality (all-cause and CV-related). Although limited by the small number of studies focusing specifically on this population, these findings support the potential therapeutic relevance of SGLT2i in patients with coexisting T2DM and gout, contributing to the management of both conditions and the reduction of CV-related events associated with them.

Myocardial infarction (MI) triggers persistent inflammatory dysregulation, wherein macrophages undergo glycolytic reprogramming and adopt an inflammatory phenotype that impairs cardiac repair. However, the specific metabolic drivers underlying post-MI macrophage dysfunction remain unclear. Here, we identify enolase 1 (ENO1)-a glycolytic enzyme up-regulated in post-MI macrophages-as a critical regulator of macrophage metabolic fate and inflammatory function. To intervene, we engineered an acid-responsive nanocarrier (PECS) that externalizes phosphatidylserine within the acidic infarct microenvironment, facilitating selective macrophage uptake. Intracellular delivery of siENO1 suppressed glycolytic flux, thereby curbing lactate accumulation and relieving its metabolic inhibition of KLF4, which initiated anti-inflammatory reprogramming. In vivo, PECS-loaded siENO1 (siENO1@PECS) treatment attenuated infarct size, fibrosis, and cardiomyocyte apoptosis while improving ventricular function. Collectively, these findings identify ENO1 as a critical metabolic checkpoint in post-MI macrophage regulation and demonstrate a bioresponsive nanocarrier strategy for precise gene modulation to enhance cardiac repair.

Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that, for the immunohistochemical images shown in Fig. 3 on p. 1070, the 'SOCS3/HD/16W' and 'SOCS3/CD/28W' images were apparently the same, albeit with differently coloured shading, suggesting that this figure had been assembled incorrectly. In addition, upon analyzing the data in this paper independently in the Editorial Office, it came to light that one of the histological images featured in Fig. 2A (the 'Oil Red O/12W' image) apparently reappeared in a paper written by different authors at different research institutes in the journal Redox Biology several years after the publication of this article, albeit the image in that paper did not feature the same level of clarity. The authors have been contacted by the Editorial Office to offer an explanation for the apparently incorrect assembly of the data in Fig. 3, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Molecular Medicine 31: 1066‑1074, 2013; DOI: 10.3892/ijmm.2013.1323].