Search Results (308)

‘Korlaxiangli’ pear occupies a pivotal position in the pear industry of Xinjiang, with both its cultivation area and total output ranking first in the region. However, ‘Korlaxiangli’ is vulnerable to freezing injury and has suffered frequent frost damage in recent years. A cold-tolerant superior individual plant was identified via preliminary field surveys and designated as cold-tolerant superior line 15-25-15 (abbreviated as ‘HY15’). To facilitate the large-scale application of this germplasm, tissue culture technology was adopted for its rapid propagation. Using spring-collected young shoots and autumn-collected dormant buds as explants, the optimal proliferation medium was determined to be DKW supplemented with 1.0 mg/L of 6-BA and 0.5 mg/L of NAA, while the optimal rooting medium was identified as 1/2 MS containing 2.5 mg/L of NAA and 15 g/L of sucrose. Transcriptome analysis revealed eight candidate genes potentially associated with shoot proliferation, among which ARF3 and ARR12 might be associated with high proliferation efficiency. This study provides a theoretical foundation and practical technical support for the conservation, genetic improvement, and establishment of efficient propagation systems of elite pear germplasm resources. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with rising prevalence in the Middle East. Real-world comparative data on disease-modifying therapies from this region remain limited. This retrospective study compared the clinical outcomes and tolerability of fingolimod and interferon beta-1a (IFN-β1a) among patients with relapsing–remitting multiple sclerosis treated at a large public referral hospital in Jordan. Materials and Methods: All eligible RRMS patients received fingolimod or IFN-β1a at a single tertiary hospital. The annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and adverse effect frequencies were analyzed using descriptive and inferential statistics. A full-cohort inclusion approach was applied instead of sample-size calculation, as all available cases at Al-Basheer Hospital (Amman, Jordan) were included. Results: Fingolimod-treated patients showed a significantly higher ARR than those on IFN-β1a (0.51 vs. 0.26, p = 0.016), an association likely influenced by treatment sequencing and baseline disease activity. EDSS distributions were similar between treatment groups, with most patients demonstrating mild disability (EDSS ≤ 3.5). IFN-β1a was linked to injection site reactions, while fingolimod was better tolerated. Conclusions: The higher observed relapse rate among fingolimod-treated patients possibly reflects treatment sequencing and underlying disease severity rather than pharmacologic efficacy, as fingolimod was commonly prescribed as an escalation therapy. These findings highlight the importance of individualized treatment selection and underscore the need for prospective studies incorporating standardized baseline disease activity measures to better inform multiple sclerosis care in Jordan and the wider Middle Eastern region. Full article

Background: The aim of the study is (1) to assess safety of opioids in nursing mothers after cesarean delivery and in breastfed infants and (2) to evaluate the role of CYP2D6 genetics in maternal and infant clinical outcomes after cesarean delivery. Methods: A total of 210 mother–infant dyads were enrolled after cesarean delivery. Oxycodone 5 mg orally was administered every 4–6 h as needed as part of a standardized opioid-sparing ERAS protocol. Primary outcomes were opioid-related adverse effects, including maternal respiratory depression (RD) and postoperative nausea and vomiting (PONV) and neonatal composite side effects (i.e., RD monitoring, sedation, and limpness). Results: In total, 77% of mothers received opioids during postpartum hospital stay, none experienced respiratory depression, 13% reported PONV, and composite opioid-related side effects were observed in 13% of neonates. Compared to mothers without opioid consumption, higher in-hospital opioid consumption was borderline significantly associated with a higher risk of neonatal composite side effects (adjusted relative risk, aRR = 3.79; 95%CI: 1.01–14.28; p = 0.07), with a similar trend toward higher risk in maternal PONV (aRR = 2.56; 95%CI: 0.70–9.29; p = 0.36). Mothers with a CYP2D6 ultra-rapid metabolizer phenotype also showed higher rates of PONV and neonatal composite side effects compared with normal or intermediate phenotypes, although these associations were not statistically significant. Conclusions: Higher maternal in-hospital opioid consumption is associated with a higher risk of neonatal composite side effects. Using the lowest effective doses of opioids as needed could reduce the risk of opioid-related side effects in neonates. Preoperative genotyping may help identify mothers and breastfed neonates at increased risk for opioid-related adverse outcomes. Additional studies are needed to evaluate preoperative genotyping and to evaluate the causality of increased neonatal adverse outcomes. Full article

Background/Objectives: Women treated with loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk of HPV detection during follow-up. We assessed whether HPV vaccination was associated with HPV positivity at the first post-treatment follow-up after LEEP. Methods: This retrospective population-based cohort included women aged 20–79 years treated by LEEP in Troms and Finnmark, Norway, during 2022–2024 (n = 1052). Vaccination status, timing, and vaccine product were obtained from the national immunization register (SYSVAK). Follow-up HPV results (overall HPV, HPV16, HPV18, and pooled other HPV types; Roche cobas 4800 channels) were retrieved from SymPathy. Results: Overall, 329/1052 women (31.3%) were HPV-positive at first follow-up. HPV positivity was 37.7% (200/530) among unvaccinated women and 24.7% (129/522) among vaccinated women (ARR 13.0 percentage points; 95% CI 7.5–18.6; RR 0.655; 95% CI 0.544–0.788; p = 5.2 × 10⁻⁶). HPV16 was detected in 5.9% vs. 9.4% (p = 0.0335), and pooled other HPV types in 18.0% vs. 28.7% (p = 4.3 × 10⁻⁵); HPV18 did not differ (2.9% vs. 2.5%; p = 0.671). In adjusted analyses, vaccination in the year of LEEP was associated with lower risk of follow-up HPV positivity (aRR 0.592; 95% CI 0.444–0.789; p = 0.000348). Conclusions: HPV vaccination before the first post-treatment follow-up was associated with lower HPV positivity after LEEP. As this outcome is a surrogate endpoint and residual confounding is possible, studies with standardized follow-up and long-term clinical endpoints are needed. Full article

The mechanism of generation of products with opposite handedness in the reactions of heterocyclic aldehydes with diallylboronates was studied by NMR experiments and DFT computations. The origin of this unusual phenomenon is a competition between monomeric and dimeric autoinductors that promote the formation of opposite enantiomers. Thus, NMR data suggest that racemic alcohol 3a, upon dimerization, provides almost exclusively the heterochiral dimeric boronate 5a(RS). This corresponds to the computed results predicting strongly exergonic dimerization with ΔΔG²⁹⁸ −6.5 kcal/mol. Dimerization of the chiral boronate 3a (R) with 82% ee yields 5a (RS) in which all available 3a(S) is bound. As a result, 3 species remain in the solution: (1) 5a(RS), producing a newly formed racemic product in the reaction with 1a, (2) 3a(R), reacting with 1a and yielding an R-configured newly formed product, and (3) 5a(RR), yielding selectively S-configured newly formed product according to computations. Taking into account the equilibria existing between monomers and dimers, the system is capable of demonstrating the experimentally observed random handedness of the newly formed product. Full article

The Yellow River Floodplain region of Shandong Province is dominated by silty soils that challenge geotechnical construction. Drilling–Mixing–Jetting (DMJ) Deep Cement Mixing Pile groups have been adopted to improve the geotechnical properties of the soil. This study conducted field tests to evaluate column strength and numerically investigated the effects of area replacement ratio (7.10%, 10.66% and 14.21%) and column spacing. It is observed that the DMJ-integrated columns demonstrate enhanced soil–cement strength in the Yellow River Floodplain region, with sample strengths varying between 2 and 8 MPa. The electrical resistivity of soil–cement shows a strong linear correlation (Pearson’s R > 0.75) with unconfined compressive strength. Settlement reduction ratios range between 32.11% and 94.75% and increase with higher area replacement ratio (ARR) and applied stress but decrease with larger column spacing. Bearing capacity improvement factors are found to be increased with ARR, while column spacing has minimal effect, with values between 423.89 kPa and 431.61 kPa. Lateral displacement decreased with column installation and increasing area replacement ratio (ARR), while the effect of column spacing was confined to depths near the column head. Full article

Background: Folic acid supplementation (FAS) before and in early pregnancy prevents neural tube defects, but the benefits of extending FAS to late pregnancy on pregnancy outcomes remain unclear. We aimed to investigate the associations between duration of FAS and a spectrum of pregnancy outcomes, and to determine whether the associations were modified by maternal age or pre-pregnancy body mass index (BMI). Methods: This prospective multicenter study included 15,694 singleton pregnancies. We used mixed-effects log-binomial regression models to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHDs), pre-eclampsia, preterm birth, macrosomia, small (SGA) and large for gestational age (LGA), and the interaction effects of advanced maternal age and pre-pregnancy BMI. Results: Of 15,694 women, 4523 (28.8%) did not take FAS before or during pregnancy, 2854 (18.2%) took FAS only during peri-pregnancy, 921 (5.9%) took FAS from peri- to mid-pregnancy, and 7396 (47.1%) took it through late pregnancy. Compared with women without FAS, those supplemented until mid-pregnancy were associated with lower risks of GHDs (aRR 0.84, 95% CI 0.74, 0.96) and pre-eclampsia (aRR 0.81, 95% CI 0.67, 0.97). Supplementation until late pregnancy was associated with lower risks of preterm birth (aRR 0.67, 95% CI 0.59, 0.76), SGA (aRR 0.74, 95% CI 0.63, 0.87), and LGA (aRR 0.88, 95% CI 0.79, 0.97). Among women of advanced maternal age or with overweight/obesity, supplementation until mid-pregnancy was associated with higher risk of GDM. Conclusions: Extending FAS until mid-pregnancy is associated with lower risks of GHDs and preeclampsia, and extending it until late pregnancy is associated with lower risks of preterm birth, SGA, and LGA. However, women of advanced maternal age or with overweight/obesity should be cautious about prolonging FAS. Full article

Background/Objectives: Digitalization of intensive care units (ICUs) aims to enhance patient safety and efficiency through standardized documentation, real-time data integration, and clinical decision support. This study evaluated whether the implementation of a patient data management system (PDMS) was associated with improvements in quality of care, infection prevention, and patient outcomes in a trauma ICU. Methods: We conducted a single-center, retrospective, before–after cohort study comparing a pre-digitalization period (2021–2022) with a post-digitalization period (2025). Consecutive adult trauma ICU admissions were analyzed. The exposure was unit-wide adoption of a PDMS implemented in 2024. The primary outcome was ICU length of stay (LOS); secondary outcomes included ICU mortality, nosocomial infection rates (episodes per 1000 ICU-days), ventilation- and antibiotic-days, device utilization, and infection epidemiology. Prespecified sensitivity analyses were performed. Results: A total of 108 patients were included (43 pre- and 65 post-digitalization). Baseline characteristics were comparable between groups. Median ICU LOS decreased from 13.0 to 6.0 days (p = 0.02). Mortality declined from 18.6% to 6.2% (p = 0.06), and crude infection rates decreased from 42.2 to 30.8 per 1000 ICU-days (rate ratio 0.73; p = 0.28). Adjusted analyses showed no statistically significant differences for mortality (aOR 0.40; p = 0.45), infection rates (aIRR 0.88; p = 0.68), LOS (aRR 1.04; p = 0.87), ventilation-days (aRR 0.86; p = 0.65), or antibiotic-days (aRR 0.70; p = 0.30). Per-patient rates of ventilator-associated pneumonia and bloodstream infection were significantly lower after digitalization (both p = 0.04), and Acinetobacter spp. infections decreased markedly (7 to 0 cases; p = 0.001). Findings were consistent after exclusion of ICU stays < 24 h. Conclusions: ICU digitalization was associated with shorter unadjusted ICU stays and favorable trends in infection and mortality outcomes, though adjusted analyses were neutral. Larger multicenter studies incorporating device-day denominators and time-to-event analyses are needed to confirm the causal impact of digital transformation on ICU quality of care. Full article

In the background of sustainable development in the construction industry, recycled cement mortar (RCM) has emerged as a research hotspot due to its eco-friendly features, where mechanical properties serve as critical indicators for evaluating its engineering applicability. This study proposes an artificial neural network (ANN) model optimized by intelligent algorithms, including the GWO (grey wolf optimizer), PSO (particle swarm optimization), and a GA (genetic algorithm), to predict the compressive strength of recycled mortar. By integrating experimental and prediction data, we establish a comprehensive database with eight input variables, including the water–cement ratio (W/C), cement–sand ratio (C/S), fly ash content (FA), aggregate replacement rate (ARR), and curing age. The predictive performance of neural network models with different database sizes (database 1: experimental data of RCM; database 2: experimental data of RCM and ordinary mortar; database 3: model prediction data of RCM, experimental data of RCM, and ordinary mortar) is analyzed. The results show that the intelligent optimization algorithms significantly enhance the predictive performance of the ANN model. Among them, the PSO-ANN model demonstrates optimal performance, with R² = 0.92, MSE = 0.007, and MAE = 0.0632, followed by the GA-ANN model and the GWO-ANN model. SHAP analysis reveals that the W/C, C/S, and curing age are the key variables influencing the compression strength. Furthermore, the size of the dataset does not significantly influence the computation time for the above models but is primarily governed by the complexity of the optimization algorithms. This study provides an efficient data-driven method for the mix design of RCM and a theoretical support for its engineering applications. Full article

Background/Objectives: The widespread use of antibiotics in livestock has raised concerns about commensal gut bacteria, such as lactic acid bacteria (LAB), acting as reservoirs for antimicrobial resistance. This study aimed to characterize the antibiotic resistance profiles of LAB isolated from livestock feces by combining phenotypic susceptibility testing with whole-genome sequencing (WGS) to identify antibiotic resistance genes (ARGs) and their genomic context. Methods: Four LAB strains from farm animal fecal samples were subjected to antibiotic susceptibility testing for 9 antibiotics (ampicillin, gentamicin, kanamycin, clindamycin, chloramphenicol, erythromycin, streptomycin, tetracycline, and vancomycin) using MIC determinations. WGS was performed on each isolate to detect ARGs using curated databases and to determine the chromosomal or plasmid location of these genes. Results: All four isolates exhibited phenotypic resistance to at least one antibiotic class, most frequently to aminoglycosides. However, discrepancies between phenotype and genotype were noted: resistance to aminoglycosides was common despite the absence of known aminoglycoside-resistance genes, suggesting intrinsic, uptake-related mechanisms. In contrast, one strain carried the chromosomal lsa(D) gene but remained susceptible to clindamycin. WGS revealed that all strains harbored the chromosomal van(T) gene, while one isolate carried three additional plasmid-borne ARGs—erm(B), cat(A), and tet(W)—conferring resistance to macrolide–lincosamide–streptogramin antibiotics, chloramphenicol, and tetracycline. Another strain encoded van(Y), lsa(D), and arr on its chromosome. The detection of multiple plasmid-located ARGs in a single LAB isolate highlights their potential for horizontal gene transfer. Conclusions: This study provides a detailed phenotypic and genomic insight into antibiotic resistance in gut-derived LAB from livestock. The findings highlight that commensal LAB can harbor clinically relevant ARGs—sometimes on mobile genetic elements—without always expressing corresponding resistance phenotypes. Such LAB may serve as a hidden reservoir for antibiotic resistance, raising the risk of ARG dissemination through the food chain. These results underscore the importance of vigilant monitoring and genomic screening of LAB, especially those considered for use in foods or feed, to ensure they do not contribute to the spread of antimicrobial resistance. Full article

Inhibition of agonist-induced M₂ muscarinic receptor (M₂R) activation by functional anti-M₂R autoantibodies has been associated with cardiac parasympathetic dysfunction in patients with chronic Chagas disease (CD). This study explored the allosteric nature of that inhibitory effect by assessing the ability of serum IgG from patients with CD and dysautonomia (DCD IgG) to modulate the interaction between M₂R and β-arrestins in HEK 293T cells using bioluminescence resonance energy transfer. DCD IgG alone did not stimulate arrestin-2 or arrestin-3 recruitment. When cells were preincubated with DCD IgG and then treated with carbachol, arrestin-2 translocation decreased in a concentration-dependent manner, while arrestin-3 recruitment remained unaffected. Inhibition curve analysis showed a submaximal inhibitory effect (68.1 ± 2.4%) and a Hill slope less than −1 (−4.03 ± 0.39). Carbachol concentration–response assays after preincubation with DCD IgG revealed a noncompetitive inhibition of arrestin-2 recruitment, with no change in arrestin-3 translocation. Unlikely, simultaneous exposure to DCD IgG and carbachol potentiated agonist-induced Arr-2 recruitment. We conclude that anti-M₂R autoantibodies selectively inhibit agonist-induced arrestin-2 recruitment, acting as negative allosteric modulators of agonist efficacy. The direction of autoantibody-induced allosteric modulation depends on the timing of IgG application relative to the agonist and the duration of receptor exposure to autoantibodies. Full article

Acer truncatum Bunge exhibits remarkable cold tolerance at the mature seedling stage, yet the mechanisms governing its seed germination under low-temperature conditions remain poorly understood. To elucidate the molecular and physiological mechanisms underlying low-temperature germination in A. truncatum seeds, we selected A. truncatum seeds as the experimental material. The seeds were evenly divided into two groups and subjected to germination under 25 °C (control) and 4 °C (low-temperature stress) conditions, followed by transcriptome sequencing and physiological and biochemical analyses. Transcriptome sequencing analyzed differential genes and physiological indicators. Fourteen transcription factor families were identified (ARR-B, AP2-EREBP, bHLH, NAC, FAR1, MADS, WRKY, AB13VP1, bZIP, C3H, CROS, LOB, TCP, and SBP). These regulate seed germination under abiotic/biotic stress. GO term enrichment occurred in biological processes. KEGG enrichment involved carbon metabolism, the glutathione pathway, the citrate cycle, and glycolysis. Most genes were upregulated. Citrate cycle and glycolysis correlated with seed activity, promoting germination. The glutathione cycle greatly improves the stress resistance of seed germination. There were 1804 genes that were upregulated and 8075 genes that were downregulated during seed germination. Among differential genes, CBF 5 was significantly downregulated but most WRKY families and LEA14-A were upregulated to maintain cell homeostasis. Meanwhile, GSH, SOD, POD, and proline (Pro) levels increased with prolonged stress. MDA rose initially, then declined. Soluble protein content first increased, then decreased, but remained higher than controls. Seeds germinated under low temperature, but germination potential was slightly lower than at room temperature. We propose that LEA protein, antioxidant enzymes, and Pro accumulation enhance cold tolerance. This study elucidates the physiological and molecular mechanisms underlying seed germination, advancing the understanding of cold tolerance in A. truncatum. Full article

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of hypertension and albuminuria in a cohort of people with HIV (PWHIV) with high rates of viral suppression. Methods: This is a cross-sectional study of 183 HAART-experienced PWHIV. Hypertension, defined as office systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg and albuminuria, was defined as a sex-based albumin–creatinine ratio (ACR) of >355 mg/g for females and >250 mg/g for males. Univariable and multivariable logistic regression was conducted to identify the association of hypertension and albuminuria with demographic, clinical, and HIV-specific factors. Results: The prevalence of hypertension was 43.9% (n = 74) and albuminuria was 22.4% (n = 41). In the multivariable analysis, factors independently associated with prevalence of HTN were older age, overweight/obesity, and diabetes mellitus. TDF-based ART was explored as a potential factor but did not reach statistical significance (aRR = 1.85, p = 0.065). For albuminuria, older age, diabetes mellitus, and duration of HAART (aRR = 1.03 per year) were revealed as independent predictors. Conclusions: The results of this study demonstrate that the development of hypertension is primarily driven by traditional metabolic risk factors. However, the progression to albuminuria appears to be influenced not only by these comorbidities but also by long-term HIV disease and HAART exposure. These findings underline the critical need for the screening and management of hypertension and other comorbidities to mitigate the risk of long-term cardiovascular and renal complications in this aging population of PWHIV. Full article

Background and Objectives: Evidence on epilepsy surgery from Central Asia is limited, reflecting the real-world challenges of developing this service in low- and middle-income settings. We evaluated one-year seizure outcomes after resective surgery for drug-resistant focal epilepsy at a single center in Kazakhstan, and we assessed whether the use of advanced presurgical imaging was associated with seizure freedom. Materials and Methods: A retrospective cohort study was conducted, including consecutive adults who underwent curative-intent resective epilepsy surgery from 2017 to 2023. Outcomes at 12 months or more post-surgery were classified using the Engel criteria. Logistic regression was used to examine associations between the advanced presurgical diagnostic tool and achieving an Engel class I outcome. Crude and adjusted risk ratios (RRs) for not achieving Engel I were estimated using modified Poisson regression with robust SEs. Results: Among 112 patients (median age 31 years; median epilepsy duration 19 years), 76% underwent temporal lobe procedures and 71% had lobectomies. At one year, 74 patients were seizure-free (Engel II: 15.2%, III: 11.6%, IV: 7.1%). Year-to-year Engel I rates varied without a significant linear trend from 2018 to 2023. In bivariable analyses, MRI-defined atrophy (RR, 3.14) and mixed lesions (RR, 2.62) were associated with a higher risk of not achieving Engel I, whereas longer epilepsy duration was linked to a lower risk (RR, 0.97 per year). In adjusted models, predictors of not achieving Engel I included generalized tonic–clonic seizures (aRR, 1.96), atrophy (aRR, 2.98), mixed lesions (aRR, 2.45), and undergoing any advanced diagnostic test (aRR, 3.38). Longer epilepsy durations remained protective (aRR 0.95 per year). In modality-specific logistic models, fMRI use was associated with higher odds of Engel I (aOR 3.39), and MR spectroscopy was associated with lower odds (aOR 0.33). Conclusions: In this Central Asian single-center cohort, about two-thirds of adults achieved complete seizure freedom one year after resective surgery—comparable to international benchmarks. Advanced imaging modalities showed divergent associations with outcomes, likely reflecting confounding by indication. These findings support the feasibility of effective epilepsy surgery in a low-resource context and the value of targeted use of advanced imaging. Full article

Background/Objectives: Myomectomy is the preferred treatment for women with uterine fibroids who desire to preserve their fertility. This study aimed to compare perinatal outcomes between Mexican women with and without a history of myomectomy, matched in a 1:2 ratio based on maternal age and parity. Methods: A retrospective cohort study was conducted involving women with and without a history of myomectomy who received prenatal care and delivered at a tertiary care hospital in Mexico City. Women with comorbidities such as pregestational diabetes, chronic hypertension, autoimmune diseases, nephropathy, cardiomyopathy, and cancer were excluded from the study. Group 1 consisted of women with a history of myomectomy, and Group 2 included matched women without such a history. The following perinatal outcomes were evaluated: miscarriage, preterm birth, cesarean section, obstetric hemorrhage, placenta previa, surgical adhesions, and obstetric hysterectomy. Adjusted relative risk (aRR) with 95% confidence intervals (CI) was calculated. Results: A total of 122 women were analyzed in group 1, and 244 in group 2. The risk of obstetric hemorrhage aRR 7.5 (95% CI 3.9–11.9), surgical adhesions aRR 11.8 (5.3–20.7), and placenta accreta aRR 15.3 (1.3–111) were significantly higher in Group 1 compared to Group 2. Other outcomes, including miscarriage, preterm birth, cesarean section, placenta previa, and obstetric hysterectomy, were similar between groups. Conclusions: Mexican pregnant women with a history of myomectomy have a higher risk of obstetric hemorrhage, surgical adhesions, and placenta accreta compared to those without such a history. Full article