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PubMed2026

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPARα, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPARα expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals↗

PubMed2026

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans↗

PubMed2026

Surgical outcomes and complications of fixation strategies for distal tibial fractures: a systematic review and network meta-analysis.

BACKGROUND: Multiple fixation options exist for distal tibial fractures, but the optimal approach remains controversial. Common techniques includeopen reduction and internal fixation(ORIF), minimally invasive plate osteosynthesis (MIPO), external fixation combined with limited open reduction and internal fixation (EF + LORIF), intramedullary nailing (IMN), and retrograde tibial nailing (RTN). METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched through March 19, 2026. Network meta-analysis (R v4.5.1) assessed operation time, fracture healing time, malunion, delayed union/nonunion, and infection, reporting MDs or RRs with 95% CIs. RESULTS: Eleven randomized controlled trials and 18 cohort studies (2145 patients) were included. MIPO was associated with a longer operative time and a longer time to union than IMN-IP (MD = 8.23, 95% CI 0.44-16.01; and MD = 1.02, 95% CI 0.10-1.93, respectively). For malunion, ORIF had a lower risk than MIPO (RR = 0.30, 95% CI 0.11-0.82), whereas MIPO had a higher risk than EF + LORIF (RR = 3.26, 95% CI 1.08-9.80) and IMN-SP (RR = 4.03, 95% CI 1.30-12.48). ORIF, EF + LORIF, and IMN-SP also showed lower malunion risk than IMN-IP. No significant differences were observed for delayed union and nonunion. Infection risk was generally higher with ORIF and MIPO than with several comparators, particularly EF + LORIF and intramedullary nailing-based strategies. CONCLUSIONS: No single strategy was consistently superior. Operation time and impaired union ( delayed union and nonunion) did not differ significantly among techniques. MIPO may be associated with longer time to union than IMN-IP and higher malunion risk than EF + LORIF and IMN-SP. Infection risk appeared higher with ORIF and MIPO in network estimates, although several comparisons remained uncertain. Findings should be interpreted in light of imprecision and study-level heterogeneity. PROTOCOL REGISTRATION: INPLASY2025120055.

Humans↗

PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4 days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15 kcal kg FFM-1 day-1) and maintaining energy availability at 45 kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and β-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, β-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40% ± 14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗

PubMed2026

Genetic determinants of gestational diabetes mellitus in thai pregnant women: role of GCKR, CDKAL1, TCF7L2, NEDD1, and CMIP variants.

BACKGROUND: Gestational diabetes mellitus (GDM) has a high global prevalence and arises from complex interactions between genetic predisposition and environmental factors. GDM is associated with metabolic disturbances and chronic low-grade inflammation, both of which contribute to its pathogenesis. This study aimed to investigate the association between GDM and 135 single-nucleotide polymorphisms (SNPs) across 20 genes related to metabolic traits. METHODS: In this case-control study, 152 pregnant women with GDM and 684 pregnant women with normal glucose tolerance (NGT) who underwent antenatal examination at Siriraj Hospital, Bangkok, were enrolled. Clinical data and blood samples were collected from all participants. Genomic DNA was isolated and subjected to whole-genome sequencing using the DNBSEQ-T7RS high-throughput sequencing platform. Genotype analyses were performed using R software, and haplotype analyses were conducted using the online SNPStats software. RESULTS: After adjusting for maternal age and pre-pregnancy body mass index, polymorphisms in TCF7L2 (rs34872471, rs7901695, rs4506565, rs7903146, rs12243326, and rs12255372), NEDD1 (rs10431408, rs11830756, rs249579, rs249585, and rs4762339), CMIP (rs2306115 and rs201681534), CDKAL1 (rs4710942), GCKR (rs2293572 and rs2293571), and GCK (rs5883890) were significantly associated with the risk of GDM. Haplotype analysis demonstrated that the TCF7L2 rs12243326-rs12255372 CA haplotype was associated with a decreased risk of GDM (OR = 0.44, 95% CI: 0.23-0.81), while the NEDD1 rs249579-rs249585-rs4762339 GGT haplotype was associated with an increased risk of GDM (OR = 1.40, 95% CI: 1.08-1.82). CONCLUSIONS: These findings suggest that genetic variations in TCF7L2, NEDD1, CMIP, CDKAL1, GCK, and GCKR contribute to GDM susceptibility in the Thai population.

Humans↗

PubMed2026

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged ≥25 years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans↗

PubMed2026

Role of omentin-1 in the global proteome of porcine pituitary cells: insights into proliferation- and apoptosis-related processes.

The anterior pituitary integrates endocrine regulation, cellular growth, and adaptive responses. Adipokines, secreted mainly by adipose tissue, act as hormonal signals linking metabolism, inflammation, appetite, and reproduction. They regulate hypothalamic-pituitary-ovarian axis by modulating hormone secretion and intracellular signaling. The presence of adipokine receptors in anterior pituitary suggests local metabolic-endocrine interactions. Omentin-1, predominantly expressed in visceral adipose tissue, participates in glucose metabolism and ovarian steroid regulation. Recent findings indicate that omentin-1 modulates tropic hormones, their receptors, and adipokine balance in anterior pituitary cells. We hypothesized that omentin-1 affects protein expression and signaling pathways involved in pituitary cell proliferation and apoptosis. This study examined its effects in anterior pituitary cells from Large White and Meishan pigs. Proteomic analysis identified 230 candidate differentially abundant proteins after omentin-1 treatment: 30 downregulated and 3 upregulated in Large White pigs, and 107 downregulated and 90 upregulated in Meishan pigs, associated with enriched 116 Gene Ontology terms. Key proteins were associated with cell cycle, DNA replication, gene expression, and posttranscriptional/posttranslational regulation. Responses differed between breeds. CDK5RAP2 and SIX1 were linked to proliferative control in Large White pigs, whereas AKT1S1 and RHOA were among the proteins associated with the broader proteomic response observed in Meishan pigs. Meishan pigs showed dynamic apoptotic protein regulation, including HTRA2, PARP2, and DFFA. Complementary in vitro experiments demonstrated that omentin-1 downregulated cyclins and caspase-3, upregulated BCL2, increased BCL2/BAX ratio, and modulated ERK1/2, AKT, AMPKα, and STAT3 phosphorylation. Together, these findings suggest that omentin-1 modulates proteomic networks and intracellular signaling associated with anterior pituitary cell function during the mid-luteal phase of the estrous cycle.

Animals↗

PubMed2025

The wider erection angle in hypospadias: A neglected feature affecting surgical outcomes.

INTRODUCTION: Penile curvature often accompanies hypospadias, and numerous techniques have been described for its correction; however, in some cases, an abnormal erection angle may also be present, further exacerbating the perception of curvature. OBJECTIVE: This study investigates the significance of the erection angle in hypospadias cases and its correlation with the severity of the anomaly. STUDY DESIGN: A retrospective analysis of intraoperative photographs of hypospadias cases operated between 2019 and 2023 was performed. Erection angle was measured with a digital goniometer during a full artificial erection. Erection angles in proximal and distal hypospadias cases were analyzed and compared to data from Kinsey's subgroups representing healthy male erection angles. RESULTS: This study involved images of 68 patients, with 31 having proximal and 37 distal hypospadias. The median age of the whole group was 11 months (6-156, IQR 9). Median erection angle was 91 (63-119, IQR 11) for distal cases, whereas it was 96 (75-138, IQR 21) for proximal cases. The difference was statistically significant (p = 0.009). The erection angle distribution in our cohort, including both proximal and distal hypospadias cases, skewed toward wider angles, highlighting a distinct pattern compared to data constituted by Kinsey and Sparling. DISCUSSION: Our findings indicate that the erection angle in hypospadias is significantly wider in proximal cases, suggesting a correlation between erection angle and severity of the hypospadias. While we acknowledge the limitation of comparing our prepubertal cohort with Kinsey's adult data, the absence of evidence suggesting significant post-pubertal changes in erection angle justifies this approach. Additionally, the use of digital images for angle assessment is not a standardized technique in hypospadias evaluation; these images were initially captured for curvature assessment. Despite these limitations, our study provides novel insights into seldom mentioned association with hypospadias - a wide erection angle, emphasizing the need for further research on its implications for surgical planning and long-term outcomes. CONCLUSION: This study introduces a wider erection angle as an additional characteristic of hypospadias particularly pronounced in proximal cases. To our knowledge, this is the first focused investigation on addressing this aspect of the condition. It emphasizes the need for further research on adults with wide post-repair erection angles to explore its long-term impact on sexual function and aesthetics.

Humans↗

PubMed2026

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I² = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Humans↗

PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

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↗

PubMed2026

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4 weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45 mL/kg/min) achieved with only ~11 min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52 min/session to achieve 80% of the maximal observed effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11 min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

Journal Article↗

PubMed2026

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group × time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group × time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

Humans↗

PubMed2026

The landscape of pruning for large language models: A systematic review and unified taxonomy.

Confronting the inherent tension between the exceptional capabilities and the immense computational costs of Large Language Models (LLMs), pruning has become a crucial technique for achieving efficient deployment. However, a systematic analytical framework dedicated specifically to LLM pruning remains absent. In this paper, we aim to bridge this gap. We first elucidate the theoretical foundations that underpin the effectiveness of pruning, namely overparameterization and redundancy, and then propose a multidimensional taxonomy that organizes existing approaches along the axes of granularity, timing, and criteria. Building upon this unified perspective, we further analyze performance recovery mechanisms and the broader evaluation ecosystem, while also exploring forward-looking challenges such as interpretability, automation, and hardware-algorithm co-design. Through this comprehensive synthesis, we seek to provide an integrated and coherent analytical lens for advancing both research and practice in LLM pruning.

Large Language Models↗

PubMed2026

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8 μg/m3 (5.9), and exposures ranged from 1.3 to 46.8 μg/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7 μg/m3, 0.1 μg/m3, and 0.7 μg/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9 μg/m3) performed poorly (R2 = 0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot↗

PubMed2026

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6 months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p < 0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3 ± 8.6) min, much shorter than the early phase (89.5 ± 10.3) min (p < 0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p < 0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p > 0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans↗

PubMed2026

Application of 13C MRS demonstrates carbohydrate feeding spares muscle but not liver glycogen utilization during high-intensity interval exercise.

We examined liver and muscle glycogen utilization during high-intensity interval cycling, and the impact of carbohydrate (CHO) feeding, using noninvasive 13C magnetic resonance spectroscopy (MRS). Following 24 h of standardized dietary intake, nine male cyclists completed 8 × 5-min intervals (1-min recovery), ingesting either placebo (PLA), 60 g maltodextrin (CHO), or 60 g maltodextrin plus caffeine, taurine, l-theanine, l-citrulline, and citicoline (CHO+) in a randomized crossover design. 13C MRS and 1H imaging were performed pre- and postexercise to determine liver and muscle glycogen and liver volume, respectively. Liver glycogen utilization was not significantly different between trials (P = 0.101) despite lower postexercise plasma glucagon concentrations in CHO and CHO+ (P = 0.001). In contrast, muscle glycogen utilization was significantly lower (∼40%) with CHO feeding compared with PLA (P = 0.006), yet this sparing effect was not evident with CHO+ (P = 0.073) in accordance with a higher mean power output during the late intervals (+2.8%, P = 0.046). Plasma glucose was comparable between trials (P = 0.175), whereas plasma lactate was higher in CHO+ versus CHO (P = 0.003), alongside lower blood bicarbonate (P = 0.005), base excess (P < 0.001), and total CO2 (P = 0.004). These findings demonstrate preferential use of skeletal muscle glycogen during high-intensity interval training (HIIT), which is attenuated under conditions of CHO feeding. This sparing effect is, however, not evident with the coingestion of a caffeine-containing multi-ingredient blend, potentially due to an increased capacity to sustain higher power outputs resulting in greater glycogen utilization.NEW & NOTEWORTHY Using 13C MRS, we provide data demonstrating preferential use of skeletal muscle glycogen during HIIT. Furthermore, data show muscle glycogen utilization is attenuated with CHO feeding, yet sparing is not evident when coingesting a caffeine-containing formulation, potentially reflecting increased capacity to perform more total work rather than a direct metabolic effect of caffeine. In contrast, liver glycogen utilization was not significantly different with CHO feeding despite a modest reduction of ∼5 g versus placebo.

Male↗

PubMed2026

Efficacy and safety of Vertebral Body Sliding Osteotomy (VBSO) versus Anterior Cervical Corpectomy and Fusion (ACCF): A systematic review and meta-analysis.

Anterior cervical corpectomy and fusion (ACCF) is an established treatment for complex cervical myelopathy and ossification of the posterior longitudinal ligament (OPLL), yet it carries risks of dural injury and graft-related failure. Vertebral body sliding osteotomy (VBSO) is a novel technique that avoids direct OPLL manipulation by translating the vertebral body anteriorly to enlarge the spinal canal. Although early studies suggest VBSO may reduce complications, evidence remains limited to retrospective cohorts from the technique's developers, with no high-level synthesis directly comparing it to ACCF. We therefore conducted this meta-analysis to compare clinical outcomes, complications, and radiographic parameters between VBSO and ACCF, while critically evaluating the certainty of the evidence and its generalizability. A systematic search of PubMed, Embase, Scopus, the Cochrane Library, and Web of Science (through June 2025) identified four retrospective cohort studies (449 patients; VBSO n = 209, ACCF n = 240). A critical limitation of the included evidence is that all studies originated from a single institution (Asan Medical Center, Seoul, Korea) with overlapping enrollment periods (2006-2020), increasing the risk of duplicate patient cohorts. Furthermore, the first author (D.-H. Lee) is the same across all included studies, introducing substantial surgeon-expertise bias. Outcomes included neurological recovery, functional outcomes, complications, and radiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Neurological recovery and functional outcomes were comparable between groups. ACCF showed slightly higher postoperative JOA scores (MD -0.59, 95% CI -0.96 to -0.22; p < 0.01), though the clinical relevance is uncertain. VBSO was associated with reduced risks of graft subsidence (RR 0.23; p < 0.01), pseudarthrosis (RR 0.25; p < 0.01), revision surgery (RR 0.17; p < 0.01), and neurological deterioration (RR 0.17; p = 0.02). CSF leakage appeared to be less frequent with VBSO, but the difference was not statistically significant. VBSO was also associated with greater postoperative cervical lordosis and shorter hospital stays. However, these findings must be interpreted with extreme caution: leave-one-out sensitivity analyses revealed that the results for postoperative JOA score, neurological deterioration, and pseudarthrosis were fragile and driven by a single large study, meaning these apparent advantages may not be robust. In addition, GRADE assessment revealed very low certainty across all assessed outcomes. Given the very low certainty of evidence, the preliminary nature of the available data, the fragility of several key findings, and the critical limitations of the underlying studies (single institution, overlapping patient cohorts, developer bias, and systematic imbalance in follow-up duration), the observed differences should be considered hypothesis-generating rather than definitive. VBSO should not be considered a proven superior alternative to ACCF based on the current evidence. Prospective, multicenter, international studies with balanced follow-up durations conducted by independent surgical teams are required before broader adoption can be recommended.

Humans↗