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Responsiveness of muscle mass gain to different load intensities of resistance training in older women: A randomized crossover study.

BACKGROUND: Aging is associated with progressive declines in skeletal muscle mass (SMM) and substantial interindividual variability in adaptations to resistance training (RT). However, whether training load intensity influences hypertrophic responsiveness in older adults remains unclear. OBJECTIVE: To investigate the effects of two commonly prescribed RT loading schemes (15RM and 10RM) on estimated SMM adaptations and responsiveness in older women. METHODS: Twenty-seven older women (67.7 ± 4.9 years; 65.7 ± 10.6 kg; 154.5 ± 5.8 cm) completed two 8-week RT interventions performed at 15RM and 10RM in a randomized crossover design, separated by a 12-week detraining period. Estimated SMM was assessed using dual-energy X-ray absorptiometry. Responsiveness was operationally defined using the standard error of measurement, and participants were classified as responders (RP) or non-responders (N-RP) according to changes in estimated SMM. RESULTS: Both loading schemes promoted significant and comparable increases in estimated SMM (15RM: +0.62 ± 0.4 kg vs. 10RM: +0.43 ± 0.3 kg). Overall, 61.1% of participants were classified as responders in at least one condition, whereas 38.9% were classified as non-responders. Responsiveness status was consistent across conditions for most participants, with 48.1% classified as responders under both loading schemes and 25.9% as non-responders under both conditions. Only seven participants (25.9%) changed responsiveness status between interventions. No clear pattern indicated a greater likelihood of responsiveness with either loading scheme. CONCLUSIONS: Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.

Aged

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, β-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to <&#x2009;27.5; n&#x2009;=&#x2009;67), T2 (27.5 to <&#x2009;55.0; n&#x2009;=&#x2009;67), and T3 (55.0 to <&#x2009;127.8; n&#x2009;=&#x2009;66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85&#x2009;weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85&#x2009;weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans

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

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

Animals

Power as equal ability, knowledge and resistance: Systematic review of experiences of adults with noncommunicable diseases.

PURPOSE: To analyse subjective experiences of power of adults with noncommunicable diseases in relationships with healthcare practitioners as well as underlying facilitators and barriers of these experiences. METHODS: Systematic review (4 databases) of experiences using reflexive thematic analysis underpinned by critical realist approach. The analysis was conducted with an abductive reasoning using previous theories on social power as well as retroduction. RESULTS: Based on 24 studies, we formed three themes, which depict experiences of power as 1) the position, equal ability and freedom to make one's own choices and (re)negotiate within shared dialogue, 2) the ability to use knowledge to claim one's rights, 3) resistance. Facilitators were connected to acknowledgement as an equally valuable individual, positive healthcare practitioner attitudes and actions towards patient activity and views, safety in the relationship as well as to sufficient, clear and varied information. Main barriers were experiences of dehumanisation, negative healthcare practitioner attitudes and actions, perceived or assumed practitioner domination in interactions, lack of or incomprehensible knowledge and testimonial smothering. CONCLUSION: Results suggest that adults with noncommunicable diseases may experience power primarily as a positive power: being acknowledged as having legitimate position to make decisions and being in possession of varied knowledge through which they can gain agency to protect and claim their rights, by resisting, if necessary. Healthcare practitioners are in key position to support these experiences through positive transforming actions, while knowledge asymmetries, persistent inequality and paternalistic structures continue to hinder it.

Humans

Patient and Public Involvement and Engagement in Pediatric Health Research: A Systematic Review.

BACKGROUND: Patient and public involvement and engagement (PPIE) can increase the relevance and efficiency of research projects. An overview of PPIE approaches and implementation in pediatric research studies is needed to facilitate learning from others' experiences. OBJECTIVE: We aimed to systematically review practices in PPIE across all pediatric health research disciplines regarding characteristics and recruitment of PPIE participants, timepoints and methods used for PPIE, levels of involvement, benefits and barriers of PPIE. SEARCH STRATEGY: We searched Pubmed, EMBASE, Cochrane and PsycInfo using a comprehensive set of terms based on the concepts 'Patient and Public Involvement,' 'Health Research' and 'Pediatrics.' INCLUSION CRITERIA: We included original research articles describing PPIE implementation in pediatric health research published in English or German between 01/2003-10/2024. DATA EXTRACTION AND SYNTHESIS: Data was extracted using predefined categories and synthesized by narrative summary and thematic synthesis. PPIE reporting quality was assessed using the GRIPP2 short form checklist. MAIN RESULTS: Out of 1910 references, we included 37 original research articles, representing 35 studies. PPIE participants were mostly children, adolescents or caregivers involved in all research stages, especially in study design (89%) and recruitment (51%). Key positive impacts of PPIE on research included enhanced recruitment and retention rates and personal benefits for PPIE participants. Barriers to PPIE were financial and time resources required and challenges in recruiting representative PPIE participants. The level of involvement and PPIE reporting quality varied highly between studies. DISCUSSION: Common benefits and barriers of PPIE exist across pediatric research disciplines. Reporting quality varied highly between studies. CONCLUSIONS: PPIE is valuable in pediatric health research. Adherence to guidelines for conducting and reporting PPIE is important to enhance mutual learning. PATIENT OR PUBLIC CONTRIBUTION: PPIE input contributed to the understandability of the lay summary. The findings of this review, together with parent and public input, will inform guidelines for future PPIE activities at the authors' institutions.

Humans

Resistance versus concurrent training with three assigned protein targets in middle-aged and older women: a randomized 2 &#xd7; 3 factorial trial.

BACKGROUND: Evidence is limited regarding whether assigned protein targets modify responses to resistance training (RT) alone or to the same RT program plus cycling (concurrent training [CT]) in middle-aged and older women. This randomized 2&#x2009;&#xd7;&#x2009;3 factorial trial examined bioelectrical impedance analysis (BIA)-derived skeletal muscle mass (SMM; primary outcome), other body composition outcomes, muscular and functional performance, and cycle-derived estimated VO&#x2082;max. METHODS: In this randomized 2&#x2009;&#xd7;&#x2009;3 factorial trial, 108 women aged 40-77 years were assigned to 12 weeks of supervised RT or CT (identical RT followed by cycling) and protein targets of 0.8, 1.6, or 2.2 g&#xb7;kg-1&#xb7;d-1. Baseline-adjusted ANCOVA tested training&#x2009;&#xd7;&#x2009;protein interactions and marginal training and protein effects. Complete-case analyses included 83 participants. RESULTS: For SMM, no training-condition&#x2009;&#xd7;&#x2009;protein-target interaction (p&#x2009;=&#x2009;0.856), marginal protein-target effect (p&#x2009;=&#x2009;0.726), or marginal training-condition effect (p&#x2009;=&#x2009;0.273) was detected. CT had a lower baseline-adjusted week-12 BFP than RT (adjusted difference, -2.04 percentage points; 95% CI, -2.94 to -1.14; p&#x2009;<&#x2009;0.001). RT had a higher baseline-adjusted week-12 leg-press estimated 1-RM than CT (CT - RT: -6.68 kg; 95% CI, -8.32 to -5.04; p&#x2009;<&#x2009;0.001), whereas CT had a higher baseline-adjusted week-12 cycle-derived estimated VO&#x2082;max (adjusted difference, 4.53 mL&#xb7;kg-1&#xb7;min-1; 95% CI, 3.80 to 5.25; p&#x2009;<&#x2009;0.001). No detectable marginal protein-target effects or training-condition&#x2009;&#xd7;&#x2009;protein-target interactions were observed for the key secondary outcomes. CONCLUSIONS: No detectable differences in SMM or key secondary outcomes were attributable to assigned protein target. Compared with RT, CT favored estimated aerobic fitness and BFP, whereas RT favored leg-press strength. Because CT included additional cycling and greater exercise exposure, these differences cannot be attributed solely to training modality. Null protein findings do not establish equivalence among doses.

Humans

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n&#x2009;>&#x2009;10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63&#x2009;000/&#x3bc;L. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6&#x2009;months. TR was 20/352 (Pooled proportion&#x2009;=&#x2009;0.064 [95% CI&#x2009;=&#x2009;0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion&#x2009;=&#x2009;0.039 [95% CI&#x2009;=&#x2009;0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

Humans

Providing Feedback on Previous Pain Scores Did Not Affect Weekly Pain Variability: A Cohort-Nested Randomised Study.

BACKGROUND: Spinal pain is one of the leading causes of disability worldwide and repeated symptom monitoring is increasingly used to capture its fluctuating nature. However, repeated pain assessments may be influenced by prior responses, potentially affecting longitudinal patterns of pain reporting. This study examined whether providing feedback on prior pain scores influenced within-person variability in weekly pain intensity ratings and retention over 60&#x2009;weeks. METHODS: This randomised study evaluating a methodological feature of repeated pain assessment was embedded within a cohort of adults with spinal pain referred to an outpatient hospital clinic. Participants (n&#x2009;=&#x2009;2448) were randomised 1:1 to weekly pain intensity ratings (0-10 numerical rating scale) either with feedback ('You answered [X] last week') or without feedback. Analyses included participants with &#x2265;&#x2009;40% valid responses (n&#x2009;=&#x2009;1883), of whom 948 received feedback and 935 did not. The primary outcome was within-person variability in pain intensity, quantified using the root mean square of successive differences. Secondary outcomes included additional fluctuation metrics and the number of weeks with missing responses. RESULTS: No meaningful between-group differences were observed for the primary outcome (mean difference -0.04 points [95% confidence interval -0.08 to 0.01]) or secondary outcomes, including retention rates. Sensitivity analyses yielded consistent findings. CONCLUSIONS: Providing participants with feedback on their previous pain score did not meaningfully influence within-person pain variability or retention during 60&#x2009;weeks of weekly monitoring. These findings aid the interpretation of repeated longitudinal pain assessments by showing that the observed variability was robust to this specific study design. SIGNIFICANCE: This randomised study showed that providing participants with feedback on prior pain scores did not meaningfully alter weekly pain variability or retention during 60&#x2009;weeks of longitudinal monitoring. These findings contribute to the interpretation of repeated longitudinal pain assessments in spinal pain research and suggest that weekly pain reporting patterns are robust to prior-pain feedback during long-term symptom monitoring.

Humans

Obesity-Related Coagulation Activation in Adolescents and Children: A Systematic Review and Meta-Analysis.

UNLABELLED: Obesity is recognized as a pro-thrombotic condition, yet the extent of coagulation activation across biomarkers remains unclear. This meta-analysis evaluates the impact of obesity on parameters-D-dimer, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), factor VIII (FVIII), and endogenous thrombin potential (ETP)-in children and adults. METHODS: Sixty-four studies comprising 59,503 individuals were analyzed. Plasma biomarker levels were compared between non-obese and obese groups using standardized mean differences (SMDs), with subgroup analyses. RESULTS: D-dimer was significantly elevated in adults with obesity (SMD 1.36, 95% CI 0.47-2.25, p&#x2009;=&#x2009;0.003) and children with obesity (SMD 0.77, 95% CI 0.19-1.36, p&#x2009;=&#x2009;0.009), indicating increased fibrin turnover. Fibrinogen levels were markedly higher in both adults (SMD 1.17, 95% CI 0.14-2.20, p&#x2009;=&#x2009;0.03) and children (SMD 1.43, 95% CI 0.93-1.92, p&#x2009;<&#x2009;0.0001). PAI-1 showed the most pronounced increase in adults (SMD 2.30, 95% CI 0.1.51-3.09, p&#x2009;<&#x2009;0.0001) and children (SMD 3.54, 95% CI 1.65-5.43, p&#x2009;=&#x2009;0.0002). FVIII levels were modestly elevated (SMD 0.52, 95% CI 0.10-0.94, p&#x2009;=&#x2009;0.02), whereas vWF levels showed inconsistent changes. ETP was significantly higher in obesity, in children (SMD 1.06, 95% CI 0.24-1.88, p&#x2009;=&#x2009;0.01) and adults (SMD 0.71, 95% CI 0.46-0.97, p&#x2009;<&#x2009;0.0001). Gender-stratified data indicated higher PAI-1, fibrinogen, and ETP levels in females. CONCLUSION: Obesity is associated with increased coagulation activation, suggesting a pro-thrombotic shift. These findings support the need for age- and gender-specific research into obesity-related hemostatic alterations.

Humans

Olive leaf protein hydrolysates yield gastro-resistant peptides with antioxidant and anti-inflammatory potential: peptidomics, in vitro validation and molecular docking analyses.

Olive (Olea europaea L.) leaves are an abundant olive-oil by-product and a promising feedstock for sustainable valorisation. An olive leaf protein isolate (OLPI) from olive-leaf powder (OLP) was enzymatically hydrolysed to yield seven hydrolysates (OLPHs). All showed notable antioxidant activity as whole hydrolysate matrices (EC&#x2085;&#x2080;&#xa0;=&#xa0;0.11-0.28&#xa0;mg&#xa0;mL-1); likely reflecting the combined contribution of released peptides and co-extracted phenolic compounds; the 15-min Alcalase product (OLPH15A) showed high activity with the shortest processing time. Its INFOGEST digest (dOLPH15A) attenuated LPS-induced inflammation in Caco-2 cells, down-regulating pro-inflammatory and up-regulating anti-inflammatory genes. Peptidomics identified 7037 peptides in OLPH15A and 534 in dOLPH15A, from which twenty gastro-resistant sequences were prioritised for in silico analysis. Multi-tool prediction and docking highlighted four peptides, GAAGGIGQPL, QSAYPGTGPL, GGGAGGGDGGIL and LDAQFPGVN, with favourable predicted affinity for the TLR4/MD2 complex, suggesting that they may contribute to the observed immunomodulatory response. These findings position olive leaves as a viable source of protein hydrolysate-based ingredients with antioxidant and anti-inflammatory potential, advancing the valorisation of olive-oil by-products.

Olea

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24&#x2009;Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35&#x2009;years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5&#x2009;mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n&#x2009;=&#x2009;50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24&#x2009;months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of &#x3b1;&#x2009;=&#x2009;0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24&#x2009;months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p&#x2009;>&#x2009;0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p&#x2009;<&#x2009;0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p&#x2009;=&#x2009;0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans

F-URS with FANS versus mPCNL for 2-3&#x2009;cm UUTS: a RCT with a subgroup analysis of 2-2.5&#x2009;cm stones.

OBJECTIVE: To evaluate the safety and efficacy of flexible ureteroscopy (f-URS) with a flexible and navigable suction ureteral access sheath (FANS) compared with mini-percutaneous nephrolithotomy (mPCNL) in the treatment of 2-3&#x2009;cm upper urinary tract stones (UUTS), with a prespecified subgroup analysis for stones &#x2265;2 to <2.5&#x2009;cm. METHODS: This randomized controlled trial enrolled 326 patients with 2-3&#x2009;cm UUTS between June 2023 and December 2025. Patients were randomly assigned in a 1:1 ratio to undergo either f-URS with FANS or mPCNL. A prespecified subgroup analysis was conducted for stones measuring &#x2265;2 to <2.5&#x2009;cm. The primary outcomes were the immediate and 1-month stone-free rate (SFR). Secondary outcomes included the operative duration, decrease in haemoglobin, hospital stay, and complication rate. RESULTS: The baseline characteristics were comparable between the two groups. In the overall 2-3&#x2009;cm cohort, the FANS group achieved immediate and 1-month SFRs comparable to those of the mPCNL group. Although the operative time was longer in the FANS group, it was associated with significantly less haemoglobin loss and a shorter hospital stay, with no significant difference in infection-related complications. Notably, in the subgroup of stones &#x2265;2 to <2.5&#x2009;cm, the FANS group demonstrated a non-inferior SFR at both time points, and the operative time was not significantly longer than that of the mPCNL group. CONCLUSION: For 2-3&#x2009;cm UUTS, f-URS with FANS offers a SFR comparable to that of mPCNL, along with the advantages of reduced blood loss and shorter hospitalization. In the &#x2265;2 to <2.5&#x2009;cm subgroup, FANS shows comprehensive benefits over mPCNL. These findings support FANS as an effective alternative to mPCNL for 2-3&#x2009;cm stones and a potentially preferred option for stones measuring 2-2.5&#x2009;cm.

Humans

Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.

Genome-wide association studies on patients with depression have identified FYN and FYB, an FYN-binding protein, as being linked to depression. We have reported that experimental manipulations in gene expression in the medial prefrontal cortex (mPFC) alter stress-induced object recognition impairments in animals. Therefore, we examined the impact of alterations in FYN and FYB expression in the mPFC of adult male rats on resistance to stress-induced impairments in object recognition. Animals with virus-mediated knockdown or overexpression of Fyn in the mPFC were subjected to either a brief 20-min restraint with 20 intermittent tail shocks, which does not induce object recognition impairment, or a prolonged 60-min restraint with 60 intermittent tail shocks, which does. In an object recognition task, control rats maintained intact object recognition following a brief stress, whereas rats with Fyn knockdown or overexpression in the mPFC showed impaired object recognition. Prolonged stress impaired object recognition in both control rats and rats with Fyn knockdown or overexpression. Additionally, rats with Fyn knockdown in the mPFC exhibited fewer c-Fos-positive cells in the mPFC in response to brief stress, accompanied by a trend toward increased c-Fos in the amygdala compared with control rats. Fyn knockdown also reduced Fyb expression in the mPFC. Furthermore, Fyb knockdown in the mPFC impaired object recognition following brief stress, suggesting that the observed effects are consistent with involvement of a coupled Fyn-Fyb signaling axis rather than Fyn alone. These findings suggest that altered Fyn-related signaling in the mPFC may underlie the resistance to stress-induced object recognition impairments.

Animals

Machine learning vs. traditional methods for predicting postoperative cardiac complications after non-cardiac surgery: a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Accurate prediction of peri-operative cardiac complications is critical to optimise pre-operative decision-making. Traditional risk prediction scores, such as the Revised Cardiac Risk Index, show only modest discrimination. Machine learning can model complex, non-linear relationships but their predictive performance compared with traditional scores remains unclear. METHODS: We performed a systematic review and Bayesian network meta-analysis. The primary outcome was postoperative adverse cardiac events following non-cardiac surgery. Prediction models were assessed relative to the Revised Cardiac Risk Index. As many studies evaluated multiple versions of each model type, the highest performing ('best version') and lowest performing ('worst version') results were analysed. Models were ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: Thirteen studies evaluating 54 models and 927,113 patients were included. Machine learning approaches generally outperformed traditional risk scores. Automated machine learning ranked highest (SUCRA 96.6) showed the greatest improvement in the best version analysis (mean difference (MD) 0.28 (95%CrI 0.16-0.40)) and remained superior in the sensitivity analysis (MD 0.30 (95%CrI 0.14-0.45)). Gradient boosting models showed superior performance over the Revised Cardiac Risk Index across analysis (best version: MD 0.20 (95%CrI 0.14-0.26), worst version: MD 0.18 (95%CrI 0.12-0.25), SUCRA 82.4). The Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest score outperformed the Revised Cardiac Risk Index in the best version analysis (MD 0.16 (95%CrI 0.01-0.32)). Between-study heterogeneity was low. None of the included studies externally validated their machine learning models and only six were judged to be at low risk of bias. DISCUSSION: Most machine learning models showed better discrimination than traditional risk scores, with automated machine learning and gradient boosting models ranking highest. However, study quality, calibration reporting and absence of external validation limit immediate clinical adoption. Prospective, multicentre evaluation is required before integration of these models into peri-operative practice.

Humans

Genomic insights into end-use grain quality and nutritional traits of an ancient Indian dwarf wheat ( Triticum sphaerococcum Percival) population using a multi-locus genome-wide association study.

BACKGROUND: Triticum sphaerococcum, an ancient hexaploid wheat species, is renowned for its stress resilience and superior nutritional quality. A panel of 116&#x2009;T. sphaerococcum accessions (the largest known collection at a single site globally), with six bread wheat released varieties, was evaluated for its potential for genetic quality improvement. Field experiments were conducted under standard, heat and moisture-deficit conditions across two cropping seasons for ten grain end-use quality and nutritional traits. RESULTS: Genotypes showed highly significant differences (P&#x2009;&#x2264;&#x2009;0.001) for measured traits, with high broad-sense heritability resulting from substantial genotypic variance contributions. Triticum sphaerococcum consistently outperformed T. aestivum across environments, with moisture-deficit stress proving more detrimental to quality parameters than heat stress, while micronutrient content increased under stressed conditions. Trait correlations revealed that the gluten index (GI) correlated negatively with the grain hardness index (GHI), wet gluten (WG), and water-binding capacity (WB), while positively correlating with dry gluten (DG) and protein content (PRO), whereas grain iron (GFE), zinc (GZN), and protein showed consistent positive interrelationships. Two superior accessions, PAUTS10 (WG 35.13%, DG 13.71%, PRO 16.42%, GZN 50.89&#x2009;ppm) and Sonamoti (WG 33.33%, DG 12.92%, PRO 16.27%, GZN 56.03&#x2009;ppm), were identified, surpassing the best check variety HD3226 for quality and nutritional parameters. Multi-locus genome-wide association studies identified 30 stable quantitative trait nucleotides across environments, with candidate gene analysis revealing genes involved in transcription regulation, biosynthetic processes, metal ion homeostasis, and transport. CONCLUSIONS: Triticum sphaerococcum demonstrated superior grain quality and micronutrient potential compared with modern wheat, highlighting its value as a genetic resource for biofortification. The identification of elite accessions and stable quantitative trait nucleotides (QTNs) provides useful targets for breeding programs aimed at improving protein and micronutrient content. Integrating ancient germplasm with modern genomic tools can accelerate the development of nutritionally enhanced wheat varieties. &#xa9; 2026 Society of Chemical Industry.

Triticum

Efficacy and Safety of Once-Weekly Semaglutide 2.0&#x2009;mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0&#x2009;mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index &#x2265;&#x2009;25&#x2009;kg/m2), and treatment with basal insulin &#x2264;&#x2009;40&#x2009;units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. RESULTS: Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5&#x2009;kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p&#x2009;<&#x2009;0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p&#x2009;=&#x2009;0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). CONCLUSIONS: Once-weekly subcutaneous semaglutide 2.0&#x2009;mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

Adult

Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged &#x2265;&#x2009;18&#x2009;years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n&#x2009;=&#x2009;42 VH, and n&#x2009;=&#x2009;71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p&#x2009;=&#x2009;0.04). VANH was associated with a significantly shorter operative time (median 55&#x2009;min versus 65&#x2009;min; p&#x2009;=&#x2009;0.005), less blood loss (median 50&#x2009;mL vs. 150&#x2009;mL; p&#x2009;<&#x2009;0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p&#x2009;=&#x2009;0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p&#x2009;<&#x2009;0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p&#x2009;=&#x2009;0.34), readmission (VH 4.8% vs. VANH 8.5%; p&#x2009;=&#x2009;0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans