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Agriculture is at the center of the relationship between human societies and natural systems, acting as both a major source of greenhouse gas emissions and a sector highly sensitive to climate change. When climate change reduces agricultural yields, land-use change represents a key pathway through which human societies may adapt. Here, we coupled a climate-yield emulator with an integrated assessment model to quantify how adaptation to climate-induced yield losses reshapes the global land-use patterns. We found that adaptive responses to declining yields could substantially transform global land use. Under the Shared Socioeconomic Pathway 2-4.5 (SSP2-4.5) scenario, global cropland expands by approximately 1.2 million km2 (about 8%), largely at the expense of forests, grasslands, and pastures. This expansion is nearly five times greater under the SSP5-unconstrained scenario and is accompanied by additional warming. Even when endogenous integrated assessment model (IAM)-based adaptations are combined with additional enhanced management practices and technological advancements, land-use change remains a plausible response to compensating for yield declines. These results reveal an underappreciated risk associated with agricultural adaptation to climate change and underscore the importance of limiting temperature rise to safeguard food security while avoiding large-scale conversion of natural land.
Perilunate dislocations (PLD) and perilunate fracture-dislocations (PLFD) are uncommon but severe carpal injuries. Although open or arthroscopic-assisted reduction with capsuloligamentous repair is recommended when feasible, access to suture anchors, appropriate nonabsorbable sutures, wrist arthroscopy, and advanced imaging may be inconsistent in resource-limited trauma settings. In such circumstances, temporary K-wire stabilization without formal ligament repair may represent a pragmatic stabilization strategy. We retrospectively reviewed 11 consecutive patients with acute PLD or PLFD treated between July 2019 and June 2024 in a single-center retrospective therapeutic case series (Level IV evidence). All patients underwent attempted fluoroscopic closed reduction followed, when necessary, by open reduction. Stabilization consisted of scapholunate and lunotriquetral pinning using two 1.6-mm K-wires, without formal ligament repair; associated fractures were fixed with K-wires as indicated. Outcomes included pain (VAS), QuickDASH, PRWE, Mayo Wrist Score (MWS), wrist range of motion, and grip strength. Radiographs assessed scapholunate distance (SLD) and scapholunate angle (SLA). Mean age was 36.9 years and 81.8% of patients were male. All injuries resulted from high-energy trauma (nine road-traffic accidents and two sports-related injuries). Five patients had PLD and six had PLFD. Closed reduction was successful in three cases; eight required open reduction (six dorsal and two combined dorsal-volar). Mean follow-up was 50.5 months. Mean VAS was 3. Mean QuickDASH was 30.4, PRWE 37.5, and MWS 78.5. Mean flexion-extension arc was 101.8° and mean grip strength was 75.2% of the contralateral side. Mean SLD was 3.0 mm and mean SLA was 61.8°. No pin-tract infection, K-wire migration, avascular necrosis, or radiographic osteoarthritis was observed at mid-term follow-up. In this small Level IV case series, isolated K-wire stabilization without formal ligament repair was associated with heterogeneous mid-term outcomes after acute PLD and fracture-dislocations. Partial functional recovery was observed in many patients, but residual scapholunate malalignment persisted in some cases. These findings are descriptive and hypothesis-generating and should be interpreted cautiously in the absence of a comparative cohort. They should not be viewed as evidence of equivalence to ligament-repair techniques.
Living things are highly complex and organised. This is often taken as an objection to reductionism and a point in favour of organicist views, which argue for the central role of the organism in all biological explanations. This paper argues that biological organisation often either is, or depends on, spatial structure, together with interactions among parts of the system understood in physical terms. We take spatial structure to include position, configuration, shape, directionality, and orientation of objects in space. Important features of the spatial structure of living systems include physical boundaries, such as membranes; cellular structure, which includes physical objects spatially arranged in certain ways; directionality and orientation with respect to internal and environmental signals; location, both of organisms in their environments and of components within the organism; and shape, including the shapes of organisms and their components at atomic, mesoscopic, and larger scales. The importance of spatial structure for explanations of the functioning of biological systems corroborates criticisms of genetic and molecular reductionism, but is compatible with physical reduction - the explanation of biological phenomena in physical terms - and part-whole reduction - the explanation of systems in terms of their parts, spatial structure, and interactions with each other and their environment.
This systematic review investigated the technical considerations, dosimetric feasibility, and clinical impact on hematologic toxicity (HT) associated with bone marrow (BM)-sparing radiation therapy in anal cancer. Original studies reporting associations between BM dosimetry and HT were identified from 6 databases and independently screened by 2 reviewers and reported according to the preferred reporting items for systematic reviews and meta-analyses 2020 standards. Study quality and risk of bias were appraised using Joanna Briggs Institute tools and the Grading of Recommendations, Assessment, Development, and Evaluation approach. Dosimetry analysis included active BM (ABM) structural definition, optimization strategies, and achievable dose reduction. Clinical efficacy was assessed using response measurement tools, toxicity predictors, and reported acute and late HT. Thirty-five studies met the inclusion criteria. The outer pelvic bone marrow (PBM) was the most common BM surrogate, followed by the ilium, lumbar-sacrum, and lower pelvis. Contouring variations of the lumbar-sacrum were noted in 15 studies, primarily in the L3 to L5 vertebrae and inferior sacrum/coccyx. ABM was defined in 14 studies using various imaging modalities, including fluorodeoxyglucose-positron emission tomography, computed tomography, fluorothymidine positron emission tomography, or magnetic resonance imaging scans. Dosimetric findings suggested that selective sparing of PBM or its subunits reduced PBM V10 to V20 by 0% to 47%, and ABM V3 to V45 by 2% to 14%. Clinically derived predictors highlighted the importance of limiting low-to-intermediate dose exposure to the whole pelvis and lumbar-sacrum. Dose-response modeling accounted for variation in assessment tools and study endpoints. A wide range of acute HT rates was reported, with comparable outcomes among patients treated with and without BM-sparing intensity-modulated radiation therapy. Multimodality imaging facilitates the structure delineation of PBM and its substructures. Dose reduction to these structures can be achieved by using various planning strategies and treatment techniques. Predictive model development requires a comprehensive analysis of response measures and clinical confounders. Given the multifactorial and heterogeneous nature of HT, further investigation is required to determine whether BM dose sparing translates into clinically meaningful HT reduction.
Gum Arabic (Acacia senegal) has shown a vital effect in improving glycemic, lipid, and cardiometabolic outcomes in adults. However, its overall effect remains uncertain because findings have been inconsistent across studies for weight, BMI, FBG, and HbA1c, and no quantitative meta-analysis has established its pooled effect. This study aimed to evaluate the effects of oral Gum Arabic (GA) supplementation, compared with placebo, on glycemic, lipid, and cardiometabolic outcomes in adults, including healthy individuals and those with type 2 diabetes mellitus and/or metabolic syndrome. We systematically searched PubMed, Cochrane Central, and Scopus for RCT studies comparing any dose of oral GA to Placebo or the standardized treatment. Outcomes assessed were BMI, weight, FBG, HbA1c, and lipid parameters. Statistical analysis was performed using RevMan, with I² statistics for heterogeneity with a random-effects model. Six RCTs (476 participants) met the inclusion criteria and were included. GA showed significant reduction in BMI (MD - 0.38; 95% CI: -0.47, - 0.29; p < 0.0000; I²= 0%; Fig. 2), weight (MD - 1.00; 95% CI: -1.59, - 0.41; p = 0.0009; I²= 0%; Fig. 3), and FBG (MD - 29.76; 95% CI: -51.88, - 7.65; p = 0.008; I²= 93%; Fig. 4). Sub-analysis of healthy versus non-healthy patients showed a statistically significant reduction of weight in the healthy group (MD - 0.99; 95% CI: -1.58, - 0.40; p = 0.001; I²= 0%; Fig. 10). GA showed some effect on lowering weight, BMI, and glycemic control in adults. Findings suggest that GA may be a promising nutritional intervention for managing cardiometabolic risk factors and weight reduction in adults. However, these results should be taken cautiously due to the limited number of trials, short follow-up periods, and high heterogeneity for fasting blood glucose. The online version contains supplementary material available at 10.1007/s40200-026-02034-y.
Clinical remission is increasingly recognized as a primary treatment goal in severe asthma, particularly severe eosinophilic asthma (SEA), where comorbidities such as chronic rhinosinusitis with nasal polyps (CRSwNP) contribute to persistent inflammation and treatment burden. Benralizumab, an anti-IL-5Rα monoclonal antibody, has shown efficacy in achieving sustained control in SEA, but long-term real-world data beyond 36 months remain limited. To evaluate the long-term (48-month) effectiveness of benralizumab in SEA patients, focusing on clinical remission, airway function, and reduction of background therapy, including oral corticosteroids (OCS) and inhaled corticosteroids (ICS). In this retrospective, multicenter study across 9 Italian centers, 128 adult SEA patients (mean age 57.1 years, 57% female; 59.4% with CRSwNP) were treated with subcutaneous benralizumab for up to 48 months. Clinical remission was assessed using SANI criteria: partial (pCR, meeting ≥2 of 3 criteria without OCS) and complete (cCR, all criteria fulfilled without OCS). Outcomes included annualized exacerbation rate (AER), pulmonary function (FEV1, FEV1/FVC, FEF25-75%), airway inflammation (FeNO, blood eosinophils), patient-reported outcomes (ACT, ACQ-6, AQLQ), and background therapy use. Mixed-effects regression models evaluated longitudinal changes. Benralizumab induced rapid and sustained improvements. AER decreased from 3.62 to 0.33 at 48 months; blood eosinophils were nearly undetectable throughout. FEV1 increased from 2.04 L to 2.49 L, with proportional gains in FEV1/FVC and FEF25-75%. ACT and ACQ-6 scores improved significantly (p < 0.001), and sinonasal symptoms in CRSwNP patients declined (VAS 4.70 → 2.31). OCS discontinuation was achieved in 88.5% of patients at 48 months, with mean ICS dose reduced by 35%. Overall, clinical remission was observed in 87.9% of patients, with cCR in 63.8%. Improvements were consistent regardless of ICS dose reduction. Long-term benralizumab treatment in SEA patients leads to rapid, sustained clinical remission, improved large and small airway function, and significant reduction of background therapy, including OCS and ICS. These results support the role of benralizumab as a disease-modifying therapy and highlight the feasibility of remission-based management in real-world practice.
Cervical spine mobility is an important functional outcome following surgical procedures. For single-level ACDF, several studies indicated that cervical range-of-motion is not compromised and may even improve, despite fusion of the treated segment. This study investigates the cervical mobility for two-level ACDF. Prospective, observational trial on patients prior, 3 months and 1 year after degenerative two-level ACDF concerning objective goniometric and subjective quality of their cervical range-of-motion. Pain courses for neck and arm, quality of life (SF-8, ADLs) and patient satisfaction were queried. 69 patients were analyzed (56.7 ± 11.0 years, 66.7% male). Goniometric range-of-motion worsened 3 months postoperatively in flexion-extension -11.5° (p < 0.001), lateral tilt -8.0° (p < 0.001) and rotation -3.6° (p = 0.062), regaining similar mobility to preoperative after 1 year (-1.5°, p = 0.700; -0.7°, p = 0.700; +2.9°, p = 1.000). Subjective range-of-motion improved significant after 3 months, and this improvement persisted even after 1 year. There was significant pain reduction at rest (NRS neck -1.2, p = 0.007; arm -2.0, p < 0.001) and under strain (NRS neck -1.5, p < 0.001; arm -2.9, p < 0.001) already after 3 months. Physical (+8.6, p < 0.001) and mental (+7.7, p = 0.065) component of SF-8 was improved and 92.8% were satisfied with the surgery. Two-level ACDF was not associated with deterioration in cervical spine mobility. Objective range-of-motion was temporarily reduced, returning to baseline after 1 year. Subjective mobility was already improved 3 months after surgery, accompanied by sustained pain reduction and improved quality of life. Consequently, concerns about postoperative motion reduction after two-level ACDF can be actively addressed.
This study aimed to characterize early clinical, functional, and radiographic outcomes after surgical treatment of tibial plateau fractures and to identify independent predictors of moderate-to-severe post-traumatic knee osteoarthritis (Kellgren-Lawrence (KL) grades 3-4) at 12 months, with emphasis on the relative contribution of fracture morphology and radiographic osteoarthritis severity. We conducted a retrospective analysis of prospectively collected clinical data from consecutive adults who underwent open reduction and internal fixation of tibial plateau fractures at a tertiary trauma center between March 2017 and June 2025, with twelve-month follow-up completed by mid-2026. Fractures were classified using the Schatzker system. At 12 months, patients underwent standardized clinical and imaging follow-up, including Rasmussen clinical and radiologic scores, KL grading, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the 36-Item Short Form Health Survey (SF-36) physical and social functioning domains. Group comparisons between KL grades 0-2 and 3-4 were conducted using non-parametric tests. Multivariable logistic regression identified predictors of KL grades 3-4, and multivariable linear regression explored correlates of KOOS and SF-36 physical functioning. Of 109 eligible patients, 106 (median age 43 years; 57.5% male) completed the 12-month evaluation. High-energy patterns predominated, with Schatzker types V-VI accounting for 51.8% of fractures. Median KOOS was 77; median SF-36 physical and social functioning scores were 80 and 88.5, respectively. While 80.2% of knees had KL grades 0-2, 19.8% already exhibited grades 3-4 and showed lower KOOS (median 63 vs 79) and lower SF-36 physical functioning (median 70 vs 82). In multivariable models, older age and female sex independently predicted KL grades 3-4, whereas fracture complexity did not. Moderate-to-severe osteoarthritis was the only variable independently associated with worse knee-specific and general physical function, corresponding to mean reductions of approximately 13 points in KOOS and 15 points in SF-36 physical functioning. No variable independently predicted Rasmussen clinical category. Most patients achieved satisfactory short-term outcomes after tibial plateau fracture surgery, yet nearly one-fifth exhibited moderate-to-severe radiographic osteoarthritis at the latest follow-up with clinically meaningful functional decrements. The Schatzker classification did not independently predict these outcomes, whereas early KL grades 3-4 emerged as the strongest correlate of functional impairment. Systematic integration of radiographic osteoarthritis grading with validated patient-reported outcome measures is essential for risk stratification and longitudinal follow-up planning.
Patients with type 2 diabetes (T2D) and recent ST-elevation myocardial infarction (STEMI) face accelerated atherosclerosis and a high risk of recurrent cardiovascular events. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly empagliflozin, offer proven cardioprotection in T2D. This study investigated the 3-month effects of empagliflozin on carotid intima-media thickness (CIMT) and Doppler hemodynamic parameters (resistive index [RI] and pulsatility index [PI]) in T2D patients post-STEMI. In this randomized clinical trial, 80 patients with T2D and a recent STEMI from Ayatollah Mousavi Hospital, Zanjan, Iran (from July to December 2025), were randomized in a 1:1 ratio to empagliflozin 10 mg daily or an identical placebo, in addition to standard therapy. The primary endpoint was the change in CIMT at 3 months, assessed using B-mode ultrasound. Secondary endpoints included changes in RI and PI, measured via Doppler ultrasound. Follow-up data were available for 78 patients (two deaths in the intervention arm, both unrelated to the study drug). In the primary intention-to-treat analysis (n=80), empagliflozin was associated with a significant reduction in left CIMT compared with controls (median change=-0.13 mm vs. -0.01; within-group P=0.002; between-group ΔCIMT P=0.004; ANCOVA-adjusted P<0.001) versus controls (-0.01 mm). A smaller though statistically significant difference was also observed for right CIMT (ΔCIMT, P=0.021; ANCOVA-adjusted P=0.006). These findings remained consistent in the per-protocol analysis. After Bonferroni correction, the reduction in left CIMT remained significant, whereas the effect on right CIMT became more modest. No significant changes were observed in RI or PI. Short-term empagliflozin suggested favorable changes in CIMT in high-risk T2D patients post-STEMI, without detectable effects on RI or PI.Iranian Registry of Clinical Trials: IRCT20230727058945N1.
Global mobility infrastructure is expected to expand significantly, especially in the Global South, potentially requiring a substantial share of the remaining carbon budget. However, the resource use and carbon emissions associated with the anticipated expansion of roads, railways, and other mobility infrastructure, as well as the potential of mitigation measures, have so far not been explored systematically. Using high-resolution infrastructure and mobility data, we assess seven demand- and four supply-side circular economy and decarbonization measures aiming to mitigate resource use and associated embodied CO2 emissions. We find that without demand reduction, infrastructure stocks could double or triple by 2060, with cumulative emissions reaching 10 to 20 GtCO2. We find that a global shift to rail would increase embodied emissions to 37 GtCO2 due to carbon-intensive materials. Combining mobility reduction with enhanced recycling and industrial decarbonization can cut emissions by 63% while providing adequate global infrastructure. This would help to offset increases in emissions from public transport infrastructure expansion required to reduce operational emissions. The online version contains supplementary material available at 10.1007/s44498-026-00132-x.
Though a healthy diet is the most effective solution for obesity, it is hindered by two main barriers: difficulty in accessing or preparing healthy meals and lack of portion control knowledge. This study compared two different medical nutrition therapies (home-delivered diet meal service [HDMS] combined with dietary counseling and dietary counseling solely) in terms of anthropometric measurements, biochemical parameters and eating behaviors in women with overweight or obesity who participated in a weight loss program. A non-randomized, controlled, parallel-group intervention study was conducted with 60 women aged 25-45 years, having a Body Mass Index (BMI) of 25-35 kg/m2, representing individuals with overweight and class I obesity. Participants were divided into two groups: an intervention group receiving HDMS combined with dietary counseling (n = 30) and a control group receiving dietary counseling solely (n = 30). Anthropometric measurements, bioelectrical impedance analysis (BIA), and dietary and physical activity records were monitored throughout the 8-week intervention, while comprehensive assessments including biochemical parameters (fasting blood glucose, homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile), resting metabolic rate (RMR) (FITMATE), and eating behaviors assessed using the Three-Factor Eating Questionnaire (TFEQ) were conducted at baseline, week 4, and week 8. Both groups showed significant reductions over time in body weight, BMI, waist circumference, hip circumference, body fat percentage, RMR, blood glucose, lipid parameters, and blood pressure values (P < 0.001). Although greater reductions were observed in the HDMS group, the differences between groups were not statistically significant (P > 0.05). When considering the group-time interaction, changes in waist circumference (P < 0.001), hip circumference (P < 0.05), RMR (P < 0.05), fasting blood glucose (P < 0.05), low-density lipoprotein (LDL), cholesterol (P < 0.05), and systolic blood pressure (P < 0.05) were found to be significant in the HDMS group. In addition, when examining eating behaviors, statistically significant changes were observed in the intervention group for both time effects and behavior outcomes. Uncontrolled eating and emotional eating behaviors decreased, while cognitive restraint increased (P < 0.001). Both interventions improved anthropometric and metabolic parameters, with greater reductions observed in the HDMS group; however, the differences between groups were not statistically significant. HDMS may be considered a practical approach to support weight management.
In the treatment of diseased coronary arteries, drug-coated balloons (DCBs) have emerged as a "leave nothing behind" alternative to drug-eluting stents, yet their effects on coronary plaque morphology in Acute Coronary Syndromes (ACS) are not well characterised. This systematic review evaluates the impact of DCB therapy on plaque morphology in patients presenting with ACS. A systematic search of PubMed, Cochrane Library, Scopus, and ScienceDirect identified studies reporting plaque-related outcomes following DCB treatment in adult patients with ACS. Six studies met the inclusion criteria, incorporating intravascular ultrasound (IVUS), optical coherence tomography (OCT), near-infrared spectroscopy (NIRS) or angiographic assessments of plaque burden, plaque volume, plaque area, lipid burden, or calcification. Across comparative and non-comparative studies, DCB therapy was consistently associated with favourable imaging changes, including reductions in plaque area, plaque burden, or plaque atheroma volume, and increased lumen dimensions. In studies assessing compositional characteristics, DCB therapy was linked with reductions in lipid core burden and lower calcification scores compared with stent-based strategies. However, heterogeneity in study design, imaging methods, and outcome reporting limits direct comparison between studies, and causality cannot be conclusively inferred. Available evidence suggests that DCB therapy may favourably modify plaque morphology in ACS, influencing plaque size and composition. The potential for DCBs to promote plaque regression, reduce lipid burden, and facilitate positive vascular remodelling warrants further investigation in larger, dedicated ACS cohorts. Future studies integrating advanced imaging and molecular profiling may clarify mechanistic pathways and identify patient groups most likely to benefit from DCB-based strategies.
Menopause marks the natural end of reproductive phase of women caused by decline in levels of estrogen, progesterone and other reproductive hormones. Asparagus racemosus (Shatavari) is a medicinal herb particularly known to be effective in alleviating women's reproductive health. Shatavarin IV, a steroidal saponin and a primary bioactive component in this herb, acts as a phytoestrogen by modulating the ER-alpha/ER-beta signalling, the TrkB-BDNF axis, and the Hypothalamic-Pituitary-Gonadal (HPG) and Hypothalamic-Pituitary-Adrenal (HPA) axes. In this study, the efficacy of SheVari4® on alleviating the menopause-specific endocrine dysfunction and subsequent impaired quality of life (QOL) was assessed through a randomized double-blind placebo-controlled parallel arm trial conducted on 60 pre-, peri-, and post-menopausal women. Sixty women (age 50.0 ± 7.4 years) randomized in two equal groups were administered with 100 mg SheVari4® or placebo capsules once daily for 8 weeks. Assessment of Menopause-Specific Quality of Life (MENQOL) along with domain scores across vasomotor, psychosocial, physical, and sexual function constituted primary endpoint analysis; changes in serum estradiol E2, Follicle Stimulating Hormone (FSH), progesterone, cortisol, Anti Mullerian Hormone (AMH), Sex Hormone-Binding Globulin (SHBG) and free testosterone were assessed as secondary endpoint analysis. Safety of the formulation was evaluated in terms of body mass index, blood biochemistry and liver function test. SheVari4 induced a 42.8% reduction in MENQOL versus placebo. Significant improvements in functioning (vs. placebo) were observed, respectively, across vasomotor (53.1% vs. 14.5%), psychosocial (53.6% vs. 9.9%), physical (39.2% vs. 6.5%) and sexual (29.4% vs. 10.7%) domains. The formulation also increased E2 (+36.44% vs. -2.08%) and progesterone (+0.30% vs. -2.88%) coupled with marked reduction in levels of FSH (-38.18% vs. +12.97%) and cortisol (-26.87% vs. +17.16%). Concomitantly, AMH, SHBG, and free testosterone were also favorably modulated. Blood biochemistry, liver function tests, and vital signs confirmed the broad-spectrum safety of SheVari4®. SheVari4® significantly improved menopause-specific QOL and endocrine parameters in peri- and post-menopausal women, with a well-established safety profile.
Combination stresses are the primary obstacle that plants encounter in nature. Consequently, there is an urgent need for environmentally sustainable solutions. Arbuscular mycorrhizal fungi (AMF) constitute one such eco-friendly approach for promoting agricultural sustainability under heavy metals (HMs) contamination, drought, heat, and salinity stress conditions, owing to their well-documented role as biostimulants. Therefore, the present investigation aimed to assess the impact of combined HMs (Cr, Pb, and Cd; each at 100 mg L- 1) and salt stress (100 mM NaCl) on lettuce and to evaluate the potential of AMF inoculation to mitigate these combined stresses. AMF colonization effectively mitigated this adverse effect, as evidenced by increases in shoot fresh weight (12.97%), total pigment (76.74%), relative water content (RWC, 10.98%), glycine betaine (GB, 21.04%), and phenolic content (15.68%). Conversely, a substantial decrease in stress markers was observed, including lipid peroxidation (MDA, 11.03%), H2O2 content (20.66%), and reductions in the antioxidant enzymes (23.56% in POD, 22.38% in PPO, and 14.73% in phenylalanine ammonia-lyase [PAL]). The Start codon targeted (SCoT) analysis demonstrated that all of these were associated with a 51% retention of genome integrity, and the percentage of damaged nuclei was reduced by 25.78%, as confirmed by the comet assay. Both easily extractable (EE, 29.58%) and total extractable (TE, 36.42%) glomalin content were significantly increased by AMF colonization upon stress. Although AMF-colonized roots exhibited a higher concentration of Pb, Cr, and Cd during combined stress, the concentration of these metals in the shoots was lower. This reduction was attributed to the ability of AMF to reduce the root-shoot translocation by 74.39, 61.42, and 56.92% for Cr, Pb, and Cd, respectively. This method could be used to cultivate lettuce in contaminated locations by trapping HMs and Na+ ions in the roots, which are not edible, while allowing the edible shoots to develop. Thus, AMF could be used to protect food safety and agricultural output in contaminated areas.
Left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative to oral anticoagulation for stroke prevention in atrial fibrillation (AF). While early randomized trials established non-inferiority of LAAC versus warfarin, the comparative effectiveness of LAAC against contemporary direct oral anticoagulants (DOACs) remains less well characterized. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing percutaneous LAAC with oral anticoagulation-either warfarin or DOACs-in adults with non-valvular AF. PubMed/MEDLINE, Embase, and CENTRAL were searched from inception through May 2026. The primary outcome was a composite of stroke, systemic embolism (SE), and cardiovascular death. The key secondary outcome was major bleeding. Five RCTs comprising 6,116 patients were included. Pooled analysis demonstrated no significant difference between LAAC and oral anticoagulation for the composite primary outcome (RR 0.90; 95% CI 0.71-1.14; I²=34%). LAAC was associated with a statistically significant 24% reduction in major bleeding events compared with anticoagulation (RR 0.76; 95% CI 0.61-0.94; I²=0%). Individual secondary outcomes, including cardiovascular death, stroke, and SE, were not significantly different between groups. Subgroup analysis by anticoagulant class suggested a larger composite efficacy benefit of LAAC over warfarin (RR 0.69) than over DOACs (RR 0.98), consistent with the established intracranial hemorrhage reduction conferred by DOACs relative to warfarin. In conclusion, LAAC achieves comparable thromboembolic protection to oral anticoagulation while significantly reducing major bleeding, supporting its role as a viable alternative in appropriately selected patients with AF, particularly those at elevated bleeding risk.
Background and objective Sounds carrying inaudible high-frequency components (HFCs) above 20 kHz can alter brain activity, autonomic tone, and subjective state, a cluster of responses termed the hypersonic effect. However, only single physiological domains have been examined till now; therefore, whether central, autonomic, and subjective indices move together under one stimulus in the same participants remains unresolved. This study measured electroencephalographic (EEG), heart rate variability (HRV), and subjective responses simultaneously to characterize the layered response to HFC-containing sound. Methods Twenty healthy adult men completed a participant-blind crossover protocol in which the order of the two conditions was randomized and counterbalanced (10 received the wide-band sound first, 10 the audible-only sound first): an audible-band sound limited to ≤20 kHz (low frequency (LF)) and a wide-band sound containing the HFC (low frequency plus high frequency (LFHF)). Each condition comprised five minutes of pre-exposure rest, 10 minutes of sound presentation (analyzed as Audio1 and Audio2), and five minutes of post-exposure rest (Post). EEG centro-parieto-occipital (CPO) Alpha-2 relative power, normalized HRV indices, and 20 semantic-differential (SD) ratings were analyzed as changes from the pre-exposure baseline. Aligned rank transform analysis of variance (ART-ANOVA; condition × time) was used, with epoch-specific Wilcoxon signed-rank condition contrasts (Bonferroni correction, m = 3); effect sizes are the rank-biserial correlation (r). Results EEG Alpha-2 showed a trend-level main effect of condition (ART-ANOVA F = 3.59, p = 0.074), with no effect of time or condition-by-time interaction. The condition-by-time interaction was not significant; in pre-specified epoch comparisons, the condition contrast was significant during the second half of presentation (Audio2: Bonferroni-corrected p = 0.025, r = 0.657, indicating a large effect) and showed a trend after presentation (Post: corrected p = 0.089, r = 0.552). For HRV, relative low-frequency power (LF%) was significantly lower under LFHF at Post (corrected p = 0.025, r = -0.657, indicating a large effect; median difference -10.1 percentage points, 95% confidence interval -17.0 to -2.9), indicating a reduction in the relative low-frequency component of normalized HRV. None of the 20 SD items differed between conditions (all p > 0.10). Conclusions Under these conditions, HFC-containing sound was associated with a trend-level increase in posterior Alpha-2 activity, most evident in pre-specified comparisons during the second half of presentation, and a lower relative LF component of normalized HRV after exposure, without significant differences in subjective ratings. These preliminary findings suggest a possible central-to-autonomic pattern that can be quantified using noninvasive physiological recordings and support further study of HFC-containing sound as an environmental, non-pharmacological approach.
This study aimed to evaluate the clinical and radiological outcomes of tibial plateau fractures involving the medial plateau by comparing an extended medial approach with medial femoral epicondyle osteotomy (med ECO) to a conventional approach without epicondyle osteotomy (non-ECO). A retrospective cohort study was conducted at two level one trauma-centers. All fractures of the medial tibial plateau (OA/OTA Type B or C) treated with med ECO were classified according to the AO/OTA and 10-segment classification using pre-operative CT scans. A comparative cohort study was performed against non-ECO patients based on age, sex, body mass index (BMI), injury mechanism, and fracture patterns. The quality of fracture reduction was determined by post-operative CT scans. Functional outcomes and postoperative complications were assessed over a minimum follow-up of 2 years. Twenty-nine patients (mean age: 50.2 ± 10.2 years, mean follow-up 71.65 ± 18.9 months) were analyzed. Both groups consisted of patients with severe tibial plateau fractures, knee dislocations, high-velocity trauma and polytrauma and concomitant injuries requiring an average hospital stay of 24.9 ± 12.4 days. Radiological outcomes showed a medial fracture step > 2 mm in 10 cases (med ECO n = 5, non-ECO n = 5) and a gap > 5 mm in 8 cases (med ECO n = 3, non-ECO n = 5). The mean radiological Rasmussen score was 13.8 ± 2.8 (med ECO 14.1 ± 2.8 vs. non-ECO 13.4 ± 3.0, p > 0.05). The mean Knee Injury and Osteoarthritis Outcome Score (KOOS) was 60.4 ± 16.9 (med ECO 61.3 ± 12.7 vs. non-ECO 59.5 + 16.2, p > 0.05) and the International Knee Documentation Committee score (IKDC score) was 56.6 ± 16.9 (med ECO 58.8 ± 19.0 vs. non-ECO 52.6 ± 14.4, p > 0.05). Both med ECO and non-ECO demonstrated good radiological results. No significant differences were observed in clinical and radiological outcomes during follow-up. However, severe medial tibial plateau fractures are devastating knee injuries, being a challenge to the functional outcome of patients due to multiple concomitant injuries. Thus, medial epicondyle osteotomy should be reserved for specific fractures, considering the added morbidity and invasiveness associated with the procedure. Retrospective Cohort Study, Level of Evidence = III.
Experimental evidence suggests that the human endometrium expresses receptors for human chorionic gonadotropin (hCG), and activation of these receptors may enhance embryo implantation. Numerous studies have explored the effects of intrauterine hCG injection on embryo transfer (ET) outcomes; however, the impact of systemic hCG administration has been investigated in comparatively fewer studies. This study aimed to evaluate the effects of intramuscular administration of 5000 IU hCG on the outcomes of frozen-thawed ET in hormonal replacement cycles using a gonadotropin-releasing hormone (GnRH)-agonist protocol. This randomized controlled trial (RCT, registered April 22, 2021) was conducted at the ROYAN Institute, a tertiary referral center in Tehran, Iran, between July 2020 and August 2022. A total of 200 infertile women undergoing cleavage-stage frozen-thawed ET were enrolled. Inclusion criteria were age <40 years, body mass index <30 kg/m2, and the availability of at least three frozen embryos of good or excellent quality. Participants were randomly assigned to either an intervention group receiving intramuscular hCG (5000 IU administered three times: 72 hours before ET, on the day of ET, and 72 hours after ET) or a control group without hCG. A total of 188 participants completed the trial (93 in the intervention group and 95 in the control group). No significant differences were observed in implantation rate (P=0.903), chemical pregnancy (P=0.912), clinical pregnancy (P=0.999), pregnancy complications (P=0.480), preterm labor (P=0.853), or live birth rate (P=0.233). However, the miscarriage rate was lower in the intervention group. This reduction approached significance per cycle (P=0.059) and reached statistical significance per pregnancy (P=0.011). Intramuscular hCG administration in hormonal replacement cycles with a GnRH-agonist does not significantly affect overall frozen-thawed ET outcomes at the cleavage stage but may be associated with a lower miscarriage rate among those who achieve pregnancy (registration number: NCT04855383).
This study examines how macroeconomic, energy, demographic, and trade factors are associated with CO2 emissions across country income groups using World Bank World development indicators (WDI) data (1990-2023). A set of deep learning models (multilayer perceptron (MLP), recurrent neural network (RNN), long short-term memory (LSTM)) is evaluated to capture non-linear patterns, and the MLP yields the best predictive accuracy. To interpret the main predictors underlying model performance, random forest (RF) feature-importance and correlation analyses are conducted, revealing systematic heterogeneity across development stages: In lower-income countries, emission patterns are more strongly linked to the energy mix and natural-resource endowments, whereas in middle- and high-income economies they are increasingly associated with trade exposure, fuel dependence, industrial activity, and demographic pressures. These findings should be interpreted as predictive associations rather than causal effects and support the design of differentiated mitigation policies aligned with countries' structural characteristics, rather than uniform global targets, to improve both effectiveness and equity in emission reduction strategies.