Search Results (3,862)

Background/Objectives: Substance use disorder (SUD) in pregnancy is an increasingly complex public health challenge that is known to worsen maternal and neonatal outcomes. Rates of polysubstance use are steadily rising. The objective of this study was to assess the impact of co-occurring opioid and stimulant use disorder on adverse pregnancy outcomes (APOs) among inpatient pregnancy hospitalizations. Methods: We conducted a cross-sectional analysis of inpatient pregnancy hospitalizations for delivery admissions from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) from 2016 to 2020. ICD-10 codes were used to identify patients with opioid and stimulant use disorder and with APOs. APO was defined as a composite to include hypertensive disorders of pregnancy, antepartum hemorrhage, postpartum hemorrhage, preterm birth, and fetal growth restriction. Multivariable logistic regression analyses were undertaken to predict the likelihood of APOs among pregnancy hospitalizations with opioid use, stimulant use, or co-occurring (opioid and stimulant) use disorders. Sociodemographic covariates, including age, race and/or ethnicity, insurance payor type, and income level, were accounted for. Results: From 2016 to 2020, 32,602 delivery hospitalizations complicated by stimulant or opioid use disorder were identified. Of these admissions, 21,049 (64.6%) had opioid use disorder, 9472 (29.1%) had stimulant use disorder, and 2081 (6.4%) had co-occurring opioid and stimulant use disorder. In the entire cohort, the prevalence of APOs was significantly highest among pregnancy delivery hospitalizations with co-occurring opioid use and stimulant use disorder (1136/2081—54.6%, p < 0.001), as compared with opioid use disorder (8923/21,049—42.4%) or stimulant use disorder alone (4654/9472—49.1%). Rates of APOs increased in subsequent years for all cohort groups. Adjusting for relevant sociodemographic covariates, co-occurring opioid and stimulant use disorder was an independent predictor of APO (aOR 3.65; CI 95%, 3.34–3.99). In comparison, opioid use disorder and stimulant use disorder were independent predictors of APOs with a less strong correlation, aOR 2.22 (CI 95%, 2.16–2.29) and aOR 2.89 (CI 95%, 2.77–3.02), respectively. Conclusions: Patients with co-occurring opioid and stimulant use disorder have the highest exposure risk for APOs, acting as an independent predictor for APOs when adjusting for sociodemographic covariates. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of childbearing age, and active disease during pregnancy is associated with increased maternal and fetal morbidity. Belimumab is an effective biologic therapy for active SLE; however, its use during pregnancy has long been limited by the scarcity of safety data. Recent evidence and updated international recommendations suggest that belimumab may be considered in selected cases when required to maintain maternal disease control. We report the case of a woman with SLE who experienced three consecutive pregnancies with live births between 2019 and 2024 while receiving belimumab, allowing an intra-individual comparison of different exposure strategies. During the first pregnancy, belimumab was discontinued at conception and was followed by a disease flare in late pregnancy and postpartum. In the second and third pregnancies, belimumab was continued until gestational week 20 following shared decision-making with the patient; nevertheless, disease flares occurred during the third trimester of both pregnancies. All pregnancies resulted in live births at term, with no congenital anomalies, placental insufficiency, or fetal growth restriction. One neonate from the third pregnancy developed early-onset neonatal sepsis and meningitis, which resolved completely after antibiotic treatment. All children are currently growing and developing normally. This case supports a risk-adapted approach to belimumab use during pregnancy. In selected women with SLE at high risk of disease reactivation, continuation of belimumab until mid-gestation may contribute to improved maternal disease control without evident adverse fetal outcomes. Full article

Background/Objectives: Prostate cancer (PCa) cells are known to heavily depend on lipids to support their growth. We hypothesized that hyperlipidemic factors, for which inhibitors are already available and used to treat cardiovascular disease, would be dysregulated in metastatic PCa (mPCa). The goal of this case-control study, including 35 men per group, was to compare the levels of PCSK9, ANGPTL3, Apo CIII, leptin, and the lipid profile in patients with mPCa versus localized Gleason 8/9 PCa (lPCa) and patients at risk of developing PCa (controls). Methods: Protein levels were assessed using ELISAs, while lipids were measured using the Roche Cobas analytical platform. Results: The following circulating analytes were higher in mPCa: triglycerides (in mmol/L; controls 1.7 ± 1.2, lPCa 1.5 ± 0.7, mPCa 2.3 ± 1.2, p = 0.0004), Apo CIII (in µg/mL; control 110.7 ± 55.7, lPCa 115.0 ± 57.64, mPCa 159.9 ± 96.7, p = 0.0179), ANGPTL3 (in ng/mL; controls 41.7 ± 20.0, lPCa 42.8 ± 24.1, mPCa 57.3 ± 26.9, p = 0.0390), and leptin (in ng/mL, controls 9.6 ± 9.1, lPCa 8.2 ± 7.9, mPCa 17.7 ± 17.8, p < 0.0001). Surprisingly, PCSK9 levels were negatively correlated with LDL in the entire cohort. Conclusions: In this cohort of men, whole-body lipid metabolic rewiring is a feature restricted to the metastatic phase of prostate cancer, suggesting it may play a significant role in the progression toward more aggressive cancer forms. Given the availability of drugs targeting ANGPTL3 and Apo CIII, the therapeutic potential of these drugs should be evaluated in metastatic PCa. Full article

Background: Sleep disturbance and psychosocial stress are emerging contributors to hypertensive disorders of pregnancy. The present cohort was recruited during the COVID-19 period, a time marked by substantial changes in prenatal care delivery, social support, and daily routines, which may have influenced maternal sleep and stress burden. Objective: This study aimed to evaluate the independent and integrated associations between maternal sleep quality, psychological stress, and pregnancy outcomes in women at moderate to high risk for preeclampsia. Methods: In a single-center observational cohort of 170 pregnant women enrolled at 16 weeks’ gestation, sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Fitbit Sense 2™ wearable data, while stress was measured through the Perceived Stress Scale (PSS-10), Generalized Anxiety Disorder-7 (GAD-7), and morning salivary cortisol. Associations with preeclampsia, birth weight, gestational age, and NICU admission were analyzed using multivariate regression and receiver operating characteristic (ROC) models. The COVID-19 period was treated as the contextual background of recruitment rather than as a directly compared exposure. Results: Poorer subjective sleep quality (higher PSQI) correlated negatively with birth weight (r = −0.34, p = 0.008) and gestational age (r = −0.28, p = 0.04). Elevated morning cortisol was significantly associated with NICU admission (r = 0.28, p = 0.002). The combined sleep + stress model predicted birth weight (R² = 0.26, p = 0.003) and preeclampsia (pseudo R² = 0.15, p = 0.015) more accurately than individual domains, achieving an ROC-AUC of 0.86 (95% CI: 0.78–0.92). Conclusions: In high-risk pregnancies, integrated evaluation of sleep and stress parameters may improve the prediction of fetal growth impairment and preeclampsia beyond single-domain models. These findings support the incorporation of psychosocial and behavioral markers into antenatal risk stratification. Because no pre-pandemic or post-pandemic comparator group was included, the COVID-19 period should be interpreted as the contextual background of the study rather than as an independently tested exposure. Full article

Background/Objectives: Placental vascular malperfusion, on both the maternal (MVM) and fetal (FVM) side, is a key mechanism linking hypertensive disorders of pregnancy, fetal growth restriction (FGR), stillbirth, preterm neonatal death and neonatal encephalopathy. Nevertheless, clinical use and medico-legal interpretation of placental findings remain inconsistent. To summarize recent evidence on the relationship between placental vascular malperfusion, perinatal mortality and neonatal brain injury, integrating standardized placental pathology with Doppler and angiogenic biomarkers, and to outline the main medico-legal implications. Methods: A PubMed search using the string “((placenta OR placental pathology) AND (stillbirth OR fetal death) AND (maternal vascular malperfusion OR fetal vascular malperfusion))” yielded 118 records. After excluding reviews, meta-analyses, case reports (except one illustrative SARS-CoV-2 placentitis case), non-human studies and papers without original histopathology, 33 studies were included: observational cohorts and case–control studies with standardized placental assessment, autopsy series, biomarker/Doppler cohorts, mechanistic work, one randomized trial protocol and a small number of focused clinical commentaries. Results: Across these studies, MVM emerges as the dominant placental lesion in pre-eclampsia, FGR and a large proportion of stillbirths, especially in early-onset disease and in association with maternal hypertension. FVM is strongly linked to stillbirth and term neonatal encephalopathy, and specific combinations of MVM, FVM and inflammatory lesions correspond to distinct patterns of brain injury. Large population-based cohorts confirm that maternal hypertensive disorders and placental malperfusion are major upstream causes of intrauterine hypoxia and preterm neonatal death. Doppler velocimetry and angiogenic biomarkers (PlGF, sFlt-1 and their ratio) are strongly associated with an increased likelihood of underlying MVM and adverse neonatal outcomes, although their predictive performance remains probabilistic and context-dependent rather than diagnostic. Mechanistic studies suggest roles for placental genomic instability and altered decidual immunity in defective placentation. Conclusions: Maternal and fetal vascular malperfusion represent converging pathways to FGR, stillbirth, preterm neonatal death and neonatal encephalopathy. Routine, standardized placental examination, interpreted together with Doppler and biomarker data, substantially improves causal attribution and timing of injury, with direct consequences for counselling, prevention and medico-legal assessment. Full article

Gypsum (CaSO₄·2H₂O) crystallization is highly sensitive to the supersaturation pathway, which governs the balance between nucleation and crystal growth and ultimately controls growth morphology. In this study, gypsum was synthesized via two contrasting routes—diffusion-controlled crystallization and rapid precipitation—using identical reactant systems to enable a direct comparison of distinct kinetic regimes. A polycarboxylate-based superplasticizer was incorporated to investigate pathway-dependent additive effects. Time-resolved observations reveal that rapid precipitation is characterized by high nucleation density under steep supersaturation, whereas diffusion-controlled crystallization proceeds under gradually increasing supersaturation with restricted nucleation and sustained anisotropic growth. Powder X-ray diffraction confirms the formation of phase-pure gypsum under all conditions. Scanning electron microscopy shows that the presence of the superplasticizer reduces crystal number density and modifies crystal habit in both pathways, although the extent and manifestation of these effects depend strongly on the governing kinetic regime. Under diffusion-controlled conditions, the increasing superplasticizer dosage promotes the transition from elongated to more tabular morphologies, while rapid precipitation results in dense, intergrown aggregates under high supersaturation. Overall, the results demonstrate that the effectiveness of the superplasticizer is not intrinsic but depends on the crystallization pathway. These findings provide new insight into how supersaturation profiles mediate the interplay between additive interactions and growth processes, enabling improved control over gypsum crystal morphology. Full article

The microstructure and mechanical behavior during 100 °C warm rolling of the high-Zn-content Al₈₀Zn₁₄Li₂Mg₂Cu₂ alloy were investigated. The alloy plate was warm-rolled to reductions of 40%, 60%, and 80%. Hardness and tensile strength decreased continuously with increased rolling up to 60%, demonstrating work softening, followed by a slight increase at 80% reduction, indicating work hardening. Systematic characterization revealed that this non-monotonic mechanical response arises from a competition between particle-stimulated nucleation (PSN)-assisted recrystallization and dislocation-driven hardening. The multi-scale intermetallic particles in this alloy play a dual role: coarse Al₅CuLi₃ particles generate high-strain particle deformation zones (PDZs) that serve as potent PSN sites, while fine nano particles pin the recrystallized grain boundaries and restrict their growth. The unusually low PSN activation temperature is attributed to the synergistic effects of the high PDZ storage energy and the progressive subgrain rotation mechanism within the PDZ. The ability to control PSN via micro- and nano-scale intermetallics presents a viable pathway for achieving grain refinement in Al-based alloys and enhancing the machinability of high-Zn-content Al alloys. Full article

Soil- and plant-associated fungi and bacteria are an important part of many ecosystems as they can affect plant health, growth and stress tolerance. However, it remains poorly understood whether the microbiomes differ between conifer species growing in the same site conditions and between tree ecosystem compartments. The main aim of the study was to describe and compare the microbiomes of Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) H. Karst.), growing in a boreal forest common garden experiment on adjacent forest plots, to analyse the tree species effect on the composition of the needle and surface soil organic-mineral horizon microbiomes. The needle and surface soil organic-mineral horizon bacterial and fungal microbiomes were simultaneously analysed by full-length 16S and ITS sequencing on a long-read sequencing platform; however, the bacterial analysis was restricted to soil samples. The highly abundant bacterial phyla in both pine and spruce soil were Actinomycetota, Pseudomonadota, Planctomycetota and Acidobacteriota. The dominant fungal phyla in pine and spruce surface organic-mineral soil was Basidiomycota, while the needles were dominated by Ascomycota. The results showed an effect of tree species on the soil bacterial and fungal microbiomes and needle fungal microbiomes based on alpha diversity, which was higher for Norway spruce compared to Scots pine. The results indicated that Norway spruce might be able to support higher microbial diversity, which could potentially be due to differences in needle longevity, root exudates, litter input and its degradation, between pine and spruce. Furthermore, the results indicated distinct microbiomes between the soil and needle compartments. Full article

The widespread utilization of plastic materials across various industrial sectors drives a continuous increase in global polymer demand. The exponential production growth generates severe environmental challenges regarding municipal solid waste management, as substantial fractions of post-consumer residuals enter landfills due to limited recycling infrastructure. Mitigating the global environmental burden requires the implementation of advanced recovery strategies to transition polymer waste into viable secondary feedstocks. Consequently, deploying efficient sorting techniques constitutes a fundamental requirement to integrate plastic materials into formal waste management protocols and optimize recycling yields. Technological innovations currently drive the transition from traditional manual segregation towards highly sophisticated automated sensor-based sorting architectures, maximizing separation efficiency. In this context, the present study comprehensively reviews pretreatment classification techniques engineered to fractionate heterogeneous waste streams into high-purity material flows. Rather than restricting the analysis to polyolefins, this review encompasses a broad spectrum of commodity polymers predominantly found in urban solid waste environments. Full article

Background: Cardiometabolic diseases are a leading cause of premature mortality globally, yet longitudinal national mortality patterns remain insufficiently characterised in Gulf Cooperation Council settings. This study examines national trends in cardiometabolic mortality alongside health system financing, capacity, and utilization in Kuwait between 2010 and 2022. Methods: A national ecological time-series analysis used Ministry of Health administrative data covering mortality, cardiac care unit (CCU) capacity and discharges, cardiovascular procedural volumes, and MOH expenditure. Cause-specific outcomes included circulatory disease, ischaemic heart disease (IHD), cerebrovascular disease, hypertensive disease, and diabetes mellitus. Ordinary least squares regression estimated annual trends; pre-COVID restricted models (2010–2019) separated secular from pandemic-period effects. Results: All-cause deaths rose significantly from 5448 (2010) to 8041 (2022; β = +373.5/year; p = 0.001), peaking at 10,938 in 2021. Circulatory disease mortality rates increased over the full series but not pre-COVID, indicating pandemic-era acceleration. IHD death counts rose significantly in both models (β = +68.4 and +67.0/year; p < 0.01); IHD rates showed no significant trend, implicating demographic growth. Diabetes demonstrated the strongest signal: significant increases in death counts (β = +36.5/year; p < 0.001) and mortality rates (β = +0.689/100,000/year; p = 0.002), rising progressively across all time blocks. Hypertensive mortality declined significantly (β = −0.113/year; p = 0.002). MOH expenditure, CCU capacity, and CCU discharges increased significantly, demonstrating sustained structural expansion of cardiovascular services. Conclusions: Rising cardiometabolic mortality—driven prominently by diabetes—occurred alongside sustained health system expansion in Kuwait, indicating that tertiary capacity growth alone is insufficient to offset underlying epidemiological pressures. These findings underscore the urgency of strengthening upstream cardiometabolic prevention, integrated diabetes surveillance, and long-term metabolic risk control as central pillars of sustainable NCD policy. Full article

Salt stress severely restricts grape (Vitis vinifera L.) production. Serine/arginine-rich (SR) proteins, as a class of RNA-binding proteins, play important roles in plant growth, development and stress responses. However, the function and regulatory mechanism of VvSR34a in grape salt tolerance remain unclear. In this study, grape callus and cutting seedlings were used as materials to explore the role and molecular mechanism of VvSR34a in grape salt stress response. The results showed that, under 100 mM NaCl treatment, the relative level of VvSR34a in grape callus exhibited a ‘first increase and then decrease’ pattern, reaching a peak at 2 h, and the gene was localized in the nucleus. Transgenic experiments confirmed that the overexpression of VvSR34a significantly enhanced salt tolerance in grape callus and cuttings, as evidenced by better growth status, higher chlorophyll content and root activity, as well as lower electrolyte leakage and malondialdehyde (MDA) content under salt stress. In contrast, the silencing of VvSR34a significantly increased salt sensitivity in grapes. Y2H and LCI assays verified that VvSR34a physically interacts with VvCOP9. VvCOP9 may play a negative regulatory role in the salt stress response of the grapevine, and through the loss of the high salt-tolerant phenotype in the VvSR34a/VvCOP9-RNAi lines, it demonstrated that VvCOP9 is genetically upstream of VvSR34a. Furthermore, the ubiquitination and degradation assay demonstrated that VvCOP9 can significantly promote the degradation of VvSR34a. RNA-seq analysis showed that a total of 2834 differentially expressed genes and 202 alternative splicing events were detected in VvSR34a overexpression lines. These differentially expressed genes were significantly enriched in ATPase activity, redox and hormone signaling pathways. This study demonstrates that VvSR34a positively regulates salt tolerance in grapes, providing an important theoretical basis for molecular breeding of salt-tolerant grapevines. Full article

The regulation of the cardiomyocyte cell cycle is central to understanding heart regeneration. In adult mammals, cardiomyocytes withdraw from the cell cycle, limiting their ability to proliferate and repair heart tissue after injury. This process is controlled by intrinsic genetic programs and extrinsic signals, which together restrict the regenerative response in mature hearts. Understanding the mechanisms that regulate cardiomyocyte cell cycle activity is therefore critical for advancing cardiac regenerative medicine. In this review, we provide a comparative and integrated overview of cardiomyocyte cell cycle regulation in lower vertebrates and mammals, and discuss the major intrinsic factors that govern this process, including cyclin/CDK pathways, transcription factors and co-activators, oxygen and metabolic regulation, and epigenetic mechanisms. We also review the influence of hormones and growth factors, as well as the supportive roles of nonmyocyte populations in heart regeneration. By integrating findings across species, developmental stages, and regulatory levels, these findings highlight the complex regulatory network controlling cardiomyocyte proliferation and provide insight into potential therapeutic strategies for stimulating cardiac repair in the adult mammalian heart. Full article

Tumor initiation and metastatic progression are driven by context-dependent genetic alterations that disrupt tumor suppressor pathways, metabolic homeostasis, and signaling networks. However, the initial drivers that transform normal cells into malignant ones and their context dependency remain elusive. To address this, we aimed to systematically identify and characterize these drivers across cancer types, species, and microenvironments. We constructed customized clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) knockout (KO) libraries targeting high-frequency mutated and downregulated genes associated with liver hepatocellular carcinoma (LIHC) and breast carcinoma (BRCA) and conducted parallel functional screens in non-cancerous mouse and human fibroblast cell lines under two-dimensional (2D), three-dimensional (3D), and in vivo conditions. Strikingly, TP53 and NF1 emerged as pan-context drivers consistently enriched across immortalization, tumorigenesis, and metastasis in both LIHC and BRCA settings, while most other identified drivers were largely species-, tissue-, and microenvironment-specific with limited cross-model overlap. Despite this heterogeneity, all drivers converge on core pathways including epigenetic regulation, metabolic reprogramming, and growth factor signaling. Unlike prior studies on established cancer cells, this work defines the genetic barriers restricting the malignant transformation of primary normal cells, offering a new framework for early cancer evolution. Full article

Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (Fon), severely restricts the sustainable development of the global watermelon industry. While conventional chemical fungicides of this disease have triggered prominent ecological issues, Bacillus-based microbial biocontrol, which combines inherent environmental compatibility with stable control efficacy, has emerged as a key green alternative to chemical management. However, the biocontrol potential of Bacillus sonorensis against this disease has not yet been fully investigated. In this study, we isolated 56 bacterial strains from healthy watermelon rhizosphere soil, and obtained a Fon-antagonistic strain A-5 with the strongest activity (70.15% mycelial inhibition rate), which was identified as B. sonorensis via polyphasic taxonomic analysis. In vitro assays showed that the sterile fermentation filtrate of strain A-5 had a maximum 81.05% inhibition rate against Fon, and its volatile organic compounds also significantly suppressed Fon growth, with broad-spectrum antifungal activity against four common phytopathogenic fungi. Functional tests confirmed that strain A-5 could secrete cell wall-degrading enzymes, produce siderophores and synthesize indole-3-acetic acid, and 17 antimicrobial secondary metabolite biosynthetic gene clusters were identified in its genome. Pot experiments verified that strain A-5 had a 78.04% relative control efficacy against watermelon Fusarium wilt, which significantly reduced seedling disease incidence and upregulated defense-related antioxidant enzyme activities in watermelon leaves. In general, B. sonorensis A-5 is a promising novel biocontrol agent for green management of watermelon Fusarium wilt. Full article

Preterm birth interrupts critical phases of lung development and is associated with long-term alterations in respiratory structure and function. While bronchopulmonary dysplasia (BPD) has traditionally been considered the principal determinant of adverse outcomes, accumulating evidence indicates that prematurity per se contributes substantially to persistent pulmonary impairment. Lung function trajectories in preterm-born children frequently track along lower percentiles from infancy into adolescence and early adulthood, with limited catch-up growth and increased vulnerability to chronic airflow limitation. Assessment of lung function requires a developmentally tailored approach, as feasibility and interpretability vary across age groups. In infancy, non-volitional techniques such as tidal breathing flow-volume loop analysis and raised-volume rapid thoracoabdominal compression allow early evaluation of respiratory mechanics. During toddlerhood, methodological limitations persist, although emerging technologies may expand feasibility. In preschool children, impulse oscillometry enables detection of small airway dysfunction, often preceding spirometric abnormalities. From school age onward, spirometry, body plethysmography, diffusing capacity, and multiple breath washout provide complementary information on obstructive, restrictive, and gas-exchange impairments. Longitudinal studies demonstrate that reduced lung function is not confined to children with BPD and may predispose to early-onset chronic obstructive pulmonary disease-like phenotypes. Early identification of abnormal trajectories and modifiable risk factors supports structured long-term follow-up and preventive strategies. Standardization of age-specific assessment protocols and harmonization of reference values are essential to improve risk stratification and optimize long-term respiratory outcomes in this vulnerable population. Full article