Search Results (6,998)

Objectives: To systematically evaluate the efficacy and safety of intraovarian platelet-rich plasma (PRP) administration in women with diminished ovarian reserve (DOR) and related conditions, given the growing clinical interest and the conflicting evidence from uncontrolled and controlled studies. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Comprehensive searches were performed in PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus up to January 2026. Eligible studies included randomized controlled trials (RCTs), prospective cohort studies, and before–after studies investigating PRP-based interventions in women diagnosed with DOR, premature ovarian insufficiency (POI), or poor ovarian response (POR). Given the limited availability of controlled data, these populations were analyzed together with cautious interpretation. Study quality was assessed using the Joanna Briggs Institute (JBI) checklists and the Critical Appraisal Skills Programme (CASP) tool for RCTs. Pooled estimates were calculated using random- or fixed-effects models depending on heterogeneity (I²). Results: Nineteen studies involving 1794 women were included, of which two were randomized controlled trials. In single-arm and before–after analyses, PRP administration was associated with increases in serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC), as well as a reduction in serum follicle-stimulating hormone (FSH). In addition, the number of metaphase II (MII) oocytes retrieved and transferable embryos increased following PRP treatment. However, pooled analyses of controlled studies, including RCTs, did not demonstrate consistent improvements in mature oocyte yield compared with control groups. In single-arm analyses, the pooled clinical pregnancy rate and live birth rate following PRP treatment were 15.5% (95% CI: 11.1–21.2%) and 10.7% (95% CI: 6.7–16.6%), respectively. No major procedure-related adverse events were reported across included studies. Conclusions: In conclusion, intraovarian PRP is associated with improvements in ovarian reserve markers such as AMH and AFC in uncontrolled studies. However, evidence from randomized controlled trials does not demonstrate a consistent benefit in pregnancy and live birth. Well-designed RCTs with standardized protocols are needed before clinical recommendation. Full article

Donor human milk (DHM) provided by human milk banks is considered the optimal feeding alternative to mother’s own milk for premature or medically compromised infants. Before distribution, DHM is subjected to Holder pasteurization (HoP) by milk banks to eliminate potential pathogens. In this study, FT-IR, GC and GC-MS were applied to characterize changes in the volatile organic compounds (VOCs) and lipid components of human milk (HM) samples that were treated by HoP. FT-IR analysis revealed changes in specific band regions, indicating modifications to triglycerides and fatty acid (FA) organization and possible disruption of the milk fat globule membrane. There was also an increase in ester groups, suggesting that HoP increases lipid oxidation. GC analysis showed a reduction in long-chain FAs, including certain omega-3 and omega-6 polyunsaturated FAs (PUFAs). GC-MS analysis showed that HoP-treated samples contained higher levels of alkanes, aldehydes, aromatics and ketones than raw HM. Conversely, other compounds, including furans, and alkynes, were found exclusively in pasteurized HM. These results show that HoP affects the lipid and VOC components of HM, highlighting the need for research into alternative pathogen elimination strategies in human milk bank practices. Full article

The stability of subsea tunnels is governed by the strong coupling among stress redistribution, damage evolution, and seepage flow (Stress–Damage–Seepage, SDS). The dynamic interplay, especially under high water pressure, often leads to catastrophic failures, yet its mechanisms, particularly the role of support timing, remain insufficiently understood due to limitations in conventional numerical methods. This study aims to unravel the SDS coupling mechanisms during tunnel excavation under high hydraulic head, and to quantitatively investigate how support timing influences the stability of the surrounding rock within this coupled system. A coupled Computational Fluid Dynamics and Discrete Element Method (CFD-DEM) framework was employed. In this approach, excavation-induced damage, crack propagation, and fluid–particle interactions are explicitly resolved at the particle scale, whereas the macroscopic permeability evolution is captured through an imposed empirical exponential relationship. Simulations were conducted under both steady-state and transient seepage conditions with varying stress ratios and water heads. High-head transient seepage intensifies SDS coupling, dynamically redistributing seepage forces to damage zone edges and amplifying damage. Support timing critically mediates this interaction: premature support risks tensile failure at the tunnel periphery, while delayed support allows a vicious cycle of shear failure and increased inflow. Optimal “timely” support, applied after initial deformation, diverts high seepage forces inward, minimizing final damage. The spatiotemporal synchronization of transient seepage forces with damage evolution is pivotal for stability. Support timing acts as a key control variable. The CFD-DEM framework effectively elucidates these micro-mechanisms, providing a scientific basis for the dynamic design of support in high-pressure subsea tunnels. Full article

Candidemia and invasive candidiasis remain significant causes of late-onset sepsis and mortality in very-low-birth-weight infants, especially in low- and middle-income countries. This narrative review synthesizes studies published between 2008 and 2025 in Latin America, addressing epidemiology, species distribution, antifungal susceptibility patterns, risk factors, therapeutic approaches, and clinical outcomes, with international comparisons. Accordingly, we present a qualitative narrative synthesis (see Methods) rather than a formal year-over-year temporal trend quantification. Globally, five species predominate, namely Candida albicans, C. parapsilosis sensu lato (s.I.), Candida tropicalis, Nakaseomyces glabratus, and Pichia kudriavzevii, with a sustained increase in non-albicans species and growing resistance to fluconazole. In Latin America, the burden varies depending on the hospital setting; C. parapsilosis sensu lato (s.I.) predominates in NICUs, and Candidozyma auris has emerged, associated with nosocomial outbreaks and multidrug resistance. Factors such as extreme prematurity, prolonged catheter use, parenteral nutrition, and antibiotics are consistently associated with the risk of infection. Mortality remains high, influenced by diagnostic delays and species characteristics. Standardized microbiological surveillance, accurate identification, and strategies tailored to each clinical setting are required to improve outcomes in this vulnerable population. Full article

The arithmetic optimization algorithm (AOA) is a recently proposed swarm intelligence optimizer with a simple structure and few control parameters. However, the original AOA relies on a single update mechanism, which often leads to premature convergence and limited adaptability in complex optimization problems. To address these limitations, this paper proposes a multi-strategy improved arithmetic optimization algorithm (IAOA). The proposed algorithm constructs a heterogeneous strategy pool composed of six search strategies, including arithmetic update, differential evolution operators, competitive elite learning, interpolation-based acceleration, and curriculum education learning. Furthermore, an adaptive strategy regulation mechanism based on fitness improvement contribution is introduced to dynamically adjust the selection probability of each strategy. Extensive experiments conducted on the CEC2017 and CEC2022 benchmark suites demonstrate that IAOA achieves a superior optimization accuracy, convergence speed, and stability compared with several classical algorithms, recent metaheuristics, and AOA variants. Statistical tests including the Wilcoxon rank-sum test and Friedman mean rank test confirm the significance of the performance improvements. In addition, the algorithm is successfully applied to a three-dimensional path planning problem for amphibious unmanned aerial vehicles, demonstrating its effectiveness in solving complex engineering optimization problems. Full article

Fusarium ear rot (FER), caused by Fusarium verticillioides, is a devastating disease that substantially reduces maize yield and compromises kernel quality. To investigate the genetic and molecular basis of resistance, an F₂ population derived from a cross between the resistant inbred line 3IBZ2 and the susceptible inbred line KW5G321 was analysed. By integrating bulked segregant analysis sequencing (BSA-Seq) with RNA sequencing (RNA-Seq), a major quantitative trait locus (QTL), designated qFER4, was identified on chromosome 4. Genetic analysis further demonstrated that qFER4 confers resistance through partial dominance. Transcriptome profiling of the resistant line revealed 7684 and 7906 differentially expressed genes (DEGs) at 36 and 72 h post inoculation (hpi), respectively. These DEGs were significantly enriched in defence-related biological processes and pathways, including phenylpropanoid biosynthesis, jasmonic acid signalling, MAPK cascades, and plant-pathogen interactions. By combining QTL mapping with transcriptome analyses, four candidate genes within the qFER4 interval were screened. Sequence analysis identified extensive structural variations in the promoter and coding regions of Zm00001d053393, including a premature stop codon predicted to lead to a gain-of-function mutation. In contrast, the other three genes exhibited only minor promoter polymorphisms with identical coding sequences between the parental lines. Overall, this study identifies a novel major-effect QTL and candidate gene associated with FER resistance, providing a foundation for gene function and a valuable genetic resource for breeding FER-resistant maize varieties. Full article

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Full article

Background: The potent topoisomerase I inhibitor SN-38, the active metabolite of irinotecan, is limited in clinical application due to severe systemic toxicity. Prodrug strategies enabling selective activation in the tumor microenvironment offer a promising approach to improve its therapeutic index. This study aims to rationally design, synthesize, and systematically evaluate novel disulfide-based SN-38 prodrugs engineered for redox-responsive activation in hypoxic tumors. Methods: Two novel disulfide-based SN-38 prodrugs (SN-38-CSS and SN-38-LSS) were designed and synthesized; SN-38-CSS incorporates a constrained cis-piperazine-fused six-membered cyclic disulfide linker, while SN-38-LSS contains a linear disulfide tether, to differentially exploit the upregulated thioredoxin (Trx/TrxR) system in hypoxic tumor microenvironments. Results: Both prodrugs demonstrated high stability under physiological pH conditions and in human plasma, minimizing premature release. Crucially, they exhibited selective, rapid degradation in the presence of dithiol reductants (TCEP and DTT), mimicking Trx system activity, while remaining stable towards monothiols (GSH, L-Cys). In vitro cytotoxicity assays revealed that the prodrugs exhibited significantly reduced toxicity compared to SN-38 under normoxic conditions across most tested cell lines. However, under hypoxic conditions, their activity was significantly restored. Specifically, SN-38-CSS exhibited cytotoxicity comparable to SN-38 against MCF-7 and NCI-N87 cells, whereas SN-38-LSS showed lower activation efficiency. Conclusions: SN-38-CSS is identified as a promising redox and hypoxia dual-responsive prodrug candidate, highlighting the strategic use of cyclic disulfide linkers for achieving high selectivity and controlled drug release within the tumor microenvironment. Full article

In the field of oil reservoir engineering, the development of large-dip-angle reservoirs poses significant challenges due to their strong heterogeneity, pronounced gravity effects, and inefficient water flooding sweep, all contributing to suboptimal oil recovery rates. This study aims to address these challenges by focusing on the core issue of optimizing water injection development strategies for such reservoirs. A numerical simulation mechanism model is constructed based on actual large-dip-angle reservoir A, and the impact of key parameters—including reservoir dip angle, permeability, injection–production well spacing, water injection intensity, and crude oil viscosity—on oil recovery is systematically analyzed under the “water injection at structural lows and oil production at structural highs” high-pressure water injection development mode. The simulation results reveal that the oil recovery rate increases with higher dip angles, permeability, injection–production well spacing, and water injection intensity; however, excessive water injection intensity or crude oil viscosity can lead to premature water breakthrough, reducing efficiency. Using the analytic hierarchy process, the primary controlling factors are ranked as permeability > crude oil viscosity > reservoir dip angle > water injection intensity > injection–production well spacing. Furthermore, development theory charts are established to guide the selection of appropriate water injection intensities for different injection–production well distances and permeabilities. This study offers valuable theoretical insights for optimizing water injection development in large-dip-angle reservoirs, thereby enhancing oil recovery and economic benefits and laying a foundation for future research and practical applications in similar reservoir settings. Full article

Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits of antiviral therapy in extremely preterm neonates remain unclear, as this group is largely excluded from clinical trials. Case presentation: We report a case of symptomatic cCMV infection in an extremely preterm infant born at 26 weeks and 2 days of gestation to a mother with primary CMV infection during the second trimester. High CMV viral loads were detected in urine and plasma shortly after birth. On day of life (DOL) 3, respiratory deterioration required intubation, with radiological findings consistent with CMV pneumonia and positive bronchoaspirate samples. Intravenous ganciclovir was initiated on DOL 16 and administered for six weeks, followed by oral valganciclovir for six months. Treatment was associated with a favourable clinical and virological response and no significant hematological toxicity. Ophthalmologic and audiological evaluations were normal. Neurodevelopmental assessment with Bayley III at one year of corrected age demonstrated age-appropriate performance across all domains. Discussion: A structured literature review identified 10 case reports, including 13 extremely preterm infants treated for cCMV infection. Antiviral dosing regimens were heterogeneous. The most frequent manifestations prompting treatment were laboratory abnormalities (92.3%), particularly thrombocytopenia and leukopenia or neutropenia. Neuroimaging abnormalities and intrauterine growth restriction or small for gestational age were each reported in 53.8% of cases. Long-term neurodevelopmental outcomes were normal in 38.5% of infants. Conclusions: Antiviral therapy for cCMV infection with ganciclovir and valgancyclovir in premature neonates is feasible and safe with careful monitoring, and appears to provide benefits. Nevertheless, well-designed studies that include pharmacokinetics and pharmacodynamics, virologic monitoring, and long term outcomes of development, vision and hearing are urgently needed. Full article

Background and Objectives: To evaluate the impact of liver cirrhosis on pregnancy outcomes using a large-scale, propensity score-matched cohort, with adjustment for numerous confounding variables. Materials and Methods: From a total of 3,701,876 pregnancies (women aged 18–49) from 1 January 2010, to 31 December 2024, after propensity score matching, 2498 pregnancies with cirrhosis and 2498 pregnancies without cirrhosis in TrinetX database were included in our analysis. To adjust for potential confounding, pregnancies in the cirrhosis group were matched 1:1 to those without cirrhosis using propensity scores derived from demographic, lifestyle, comorbidity, and laboratory characteristics. Relative risks (RRs), risk differences (RDs), and corresponding 95% confidence intervals (CIs) were calculated for pregnancy-related outcomes. Subgroup analyses stratified by maternal age were further performed to assess potential effect modification. Main outcomes included Gestational diabetes mellitus, preeclampsia, premature rupture membranes, preterm birth, miscarriage, stillbirth, placental abruption, dystocia, postpartum hemorrhagia, and cesarean delivery. Results: After matching, 2485 women were included in each group, with well-balanced baseline characteristics. Compared with women without cirrhosis, those with cirrhosis had a higher risk of pregnancy-related outcomes, including gestational diabetes mellitus (15.5% vs. 11.9%; RR = 1.30; 95% CI, 1.13–1.50, p < 0.001), preeclampsia (8.6% vs. 5.7%; RR = 1.52; 95% CI, 1.24–1.87, p < 0.001), and preterm birth (9.0% vs. 4.9%; RR = 1.85; 95% CI, 1.49–2.29, p < 0.001). Cirrhosis during pregnancy was also associated with a higher risk of miscarriage (6.6% vs. 4.8%), stillbirth (1.3% vs. 0.5%), placental abruption (1.8% vs. 0.8%), postpartum hemorrhage (6.9% vs. 4.3%), and cesarean delivery (20% vs. 17.2%). The limitations include the lack of detailed data on cirrhosis severity. Conclusions: Pregnancy with liver cirrhosis is associated with increased risks of diverse maternal and neonatal complications. Our findings highlight the importance of multidisciplinary management and individualized care planning in order to reduce adverse outcomes. Full article

Precast reinforced concrete (RC) structures offer advantages in terms of construction efficiency and quality control; however, their seismic performance is governed by the behavior of the beam–column connections. This study presents an experimental investigation of the cyclic response of precast RC beam–column joints that include a composite steel connection, designed to enhance strength, stiffness, and damage control in critical regions. A composite joint specimen was tested under displacement-controlled cyclic loading, and its behavior was compared with that of a corresponding pure RC connection. Experimental results showed that the composite configuration effectively prevented premature failure at the beam–column interface, relocated plastic hinges away from the joint core, and significantly improved the load-carrying capacity, stiffness, and energy dissipation. To interpret the experimental observations and examine the internal stress transfer and evolution of damage, a three-dimensional nonlinear finite-element model was developed. The simulations reproduced the observed modes of failure, shapes of deformation, hysteretic responses, and moment distribution trends, particularly in the post-yield and strain-hardening ranges. Although the pinching effects observed experimentally were not fully captured numerically, the overall levels of agreement in the ultimate strength and plastic hinge locations were satisfactory. The combined results indicate that composite steel-reinforced precast beam–column joints represent a promising solution for improving seismic performance. Full article

Background/Objectives: Stroke is a leading cause of mortality and disability in Saudi Arabia; however, national estimates of stroke-related rehabilitation needs remain limited. This study quantified temporal trends in stroke incidence, prevalence, premature mortality, and disability from 1990 to 2021. It also examined disparities in stroke-related disability by subtype, sex, and age in 2021 and projected rehabilitation demand to 2030 to inform health system planning under Vision 2030. Methods: We conducted a secondary analysis of Global Burden of Disease (GBD) 2021 estimates for Saudi Arabia. Age-standardized rates for incidence, prevalence, years of life lost (YLLs), and years lived with disability (YLDs) were extracted for overall stroke and three subtypes: ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Temporal trends were evaluated using log-linear regression to estimate the average annual percentage change (AAPC). YLDs were mapped to severity levels and four rehabilitation modalities, physiotherapy (PT), occupational therapy (OT), speech–language therapy (SLT), and multidisciplinary comprehensive rehabilitation (MCR), using utilization probabilities informed by the literature. Projections to 2030 incorporated national population forecasts and included 95% prediction intervals and sensitivity analyses. Results: From 1990 to 2021, age-standardized stroke incidence declined from 166.3 to 130.7 per 100,000 (−21.4%; AAPC, −0.86%, p = 0.004), prevalence from 982.4 to 965.2 per 100,000 (−1.8%; AAPC, −0.10%, p = 0.056), and YLL rates from 3209.0 to 1893.4 per 100,000 (−41.0%; AAPC, −1.76%, p < 0.001). In contrast, YLD rates declined modestly from 133.5 to 129.9 per 100,000 (−2.7%; AAPC, −0.13%; p = 0.032). Despite these reductions in age-standardized rates, absolute stroke-related YLDs more than tripled, increasing from approximately 10,900 (95% UI: 8100–13,900) in 1990 to 36,245 (95% UI: 26,600–46,100) in 2021, largely driven by population growth and aging. In 2021, ischemic stroke accounted for 71.1% of total YLDs, followed by ICH (20.3%) and SAH (8.5%). Among adults aged 15–49 years, females had higher hemorrhagic YLD rates than males, with particularly pronounced differences for SAH (female-to-male ratio, 1.5–1.7). By 2030, the projected YLD-equivalent workload, a standardized proxy measure of relative service demand rather than a direct headcount of required therapists, is expected to increase to 29,758 for PT, 21,809 for OT, 14,879 for SLT, and 15,083 for MCR. Sensitivity analyses showed that rehabilitation demand estimates were sensitive to assumptions regarding severity distribution, with a hemorrhagic-weighted scenario increasing projected MCR demand by 6.8%. Conclusions: The increasing absolute burden of stroke-related disability in Saudi Arabia, despite declining age-standardized rates and substantial reductions in premature mortality, highlights the necessity to expand rehabilitation capacity. Scaling community-based, outpatient, and telerehabilitation services in alignment with the Health Sector Transformation Program and integrating disability-informed planning into Vision 2030 should be prioritized. Full article

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent a growing global health burden, affecting nearly one in ten adults worldwide. CKD is associated with high morbidity, premature mortality, reduced quality of life and enormous healthcare costs, and is primarily driven by dialysis and kidney transplantation. The silent and progressive nature of CKD means that most patients are diagnosed late, when irreversible damage has already occurred and costly kidney replacement therapies (KRT) become necessary. Dialysis services are resource-intensive, requiring significant infrastructure, specialized staff, and consumables, which makes them especially challenging to sustain in low- and middle-income countries. Traditional models of nephrology, care center-based dialysis and fragmented follow-up are increasingly inadequate in meeting the demands of a rising CKD population. These challenges highlight the urgent need for innovative approaches that enhance efficiency, improve patient outcomes, and expand access. Objective: This review aims to analyze the current landscape of information and communication technology (ICT) applications in nephrology and to evaluate how digital innovations are reconfiguring kidney therapy. Specifically, it seeks to identify the major ICT tools that are currently in use, assess their clinical and operational impact, and discuss their role in creating more sustainable, patient-centered kidney care models. This study reviews and analyzes ICT tools that are reconfiguring nephrology, including remote monitoring, AI, wearables, patient engagement apps and data dashboards. Methods: Narrative and scoping review of recent innovations in nephrology, including remote patient monitoring (RPM), telehealth, artificial intelligence (AI) analytics, wearable sensors, and clinical decision support platforms. Results: ICT tools such as Sharesource, Versia, telenephrology platforms, medical assistant for Chronic Care Service (MACCS), AI-based predictive analytics, wearable devices and patient engagement apps have improved patient outcomes, adherence, and early detection of complications. Key metrics include technique survival, hospitalization rate, patient-reported outcomes, workflow efficiency, and prediction accuracy. The relevant literature describing the potential of digital health technologies, including ICT platforms, artificial intelligence tools, and remote monitoring systems, to transform nephrology care was retrieved and screened for inclusion in this narrative review. Conclusions: ICT has shifted nephrology from reactive to proactive care, enhancing accessibility, patient empowerment and clinical efficiency. Future directions include precision nephrology, fully wearable kidneys, AI integration and large language models for education and triage. Challenges include digital divide, regulatory heterogeneity, cost and the need for long-term evidence. Full article

Background: The multifactorial pathogenesis of bronchopulmonary dysplasia (BPD) includes prematurity, inflammation, and oxidative stress. Photobiomodulation therapy (PBMT) using near-infrared (NIR) laser sources was found to have anti-inflammatory effects in several respiratory disorders. Our aim was to evaluate whether PBMT could reduce inflammation in an in vitro model of BPD. Materials and Methods: Precision-cut lung slices (PCLSs) from premature rabbits were exposed to lipopolysaccharide (LPS) and treated with three PBMT protocols (A, B, and C) differing for the treatment parameter such as fluence (energy delivered per unit area, laser A: 7.09, laser B: 7.41, laser C: 7.01 J/cm²) and exposure time (25, 20, 12 s, respectively). The expression level of TNFα and IL-6 was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) after 2 or 6 h from PBMT. Results: PBMT protocols A and B reduced IL-6 and TNFα mRNA at both timepoints, although the effect was less pronounced after 6 h than after 2 h. Furthermore, protocol A, which involved intermediate fluence and longer laser exposure, was more effective than protocol B. Conclusions: PBMT with NIR laser sources has an effective anti-inflammatory effect in an in vitro model of BPD, such as PCLSs from premature rabbits pretreated with LPS. These encouraging results support the planning of further studies in animal models of BPD and help identify the most effective PBMT protocol to use. Full article