Breast cancer is the most common cancer found in women including in Indonesia. Breast cancer patients are prone to have anxiety and it affects their quality of life. Interleukin-6 (IL-6) is one of the pro-tumorigenic cytokines that increases in breast cancer and is associated with worse prognosis and cancer metastasis. Several studies demonstrated the correlation between inflammatory cytokines and anxiety disorders. Therefore, this study aimed to determine the correlation between IL-6 and quality of life with anxiety syndrome in patients with late-stage breast cancer. This cross-sectional study involved women with late-stage breast cancer (Stage III and IV) in Haji Adam Malik General Hospital. IL-6 levels were assessed using Sandwich enzyme-linked immunosorbent assay (Sandwich-ELISA). The quality of life and anxiety syndromes were assessed using the European Organization for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire (EORTC QLQ-C30) and Hospital Anxiety and Depression Scale (HADS)-A questionnaire, respectively. Kruskal-Wallis test was used to determine the correlation between variables. A p-value < 0.05 was considered statistically significant. Fifty-nine women met the inclusion criteria. The analysis demonstrated that higher IL-6 levels (p < 0.001) and poor QoL (p < 0.001) were related to severe anxiety disorders in late-stage breast cancer patients. IL-6 level and quality of life were potentially used in the risk stratification and early detection of anxiety syndrome in late-stage breast cancer cases.
of this study was to evaluate the correlation between pre-treatment NLR and histopathological differentiation in colorectal cancer, and to assess the diagnostic accuracy of NLR as a predictive biomarker. A retrospective study was conducted at Adam Malik Haji Center General Hospital Medan, North Sumatera. Medical records of 45 colorectal cancer patients treated between January and December 2024 were reviewed. Pre-treatment NLR values were calculated from peripheral blood counts. Receiver Operating Characteristic (ROC) curve analysis was performed to determine diagnostic performance, and correlation analysis was used to assess the relationship between NLR and tumour grade. The mean NLR was 6.33±4.92. ROC analysis yielded an area under the curve (AUC) of 0.874, indicating excellent diagnostic ability. An NLR cutoff value of 6.25 provided a sensitivity of 87.5% and specificity of 72.5% for predicting poor histopathological differentiation. A moderate positive correlation (r=0.612; p<0.001) was found between higher NLR values and poorer differentiation. Pre-treatment NLR correlated with histopathological grade and showed promise as a simple, non-invasive biomarker for assessing tumour aggressiveness in colorectal cancer.
Serum prostate-specific antigen (PSA) concentrations decrease after hormone therapy for prostate cancer, with the nadir serving as a potentially useful prognostic biomarker. To support clinical use, we evaluated the association between PSA nadir values and survival outcomes, stratified by pre-treatment metastatic volume or, in patients with non-metastatic cancer, stratified by lymph node status. As part of the STAMPEDE platform trial, patients with metastatic or very high-risk non-metastatic prostate adenocarcinoma were recruited to five randomised, controlled, phase 3 trials conducted at 126 hospitals or oncology centres in Switzerland and the UK. Patients were randomly assigned to either standard of care (androgren deprivation therapy [ADT] alone or ADT plus docetaxel) or to one of five experimental treatment groups: ADT plus docetaxel with or without zoledronic acid, ADT plus abiraterone acetate with or without enzalutamide, or ADT plus prostate radiotherapy (only patients with metastatic disease). We used trial data from these participants to perform landmark analyses to test associations of PSA at 6, 12, and 24 weeks after randomisation with overall survival. Only patients with a PSA value were included in each landmark analysis. The Kaplan-Meier method was used to estimate 96-month overall survival rates and the corresponding 95% CIs for patients categorised by either metastatic volume or lymph node status. The STAMPEDE protocol platform is registered with ClinicalTrials.gov (NCT00268476), EUDRACT (2004-000193-31), and ISRCTN (ISRCTN78818544). This study included 7129 patients from the STAMPEDE platform, who were recruited between Oct 5, 2005, and Sept 2, 2016; 4438 had metastases and 2691 had very high-risk non-metastatic disease. Among patients with metastasis and volumetric assessment, 2211 (55·9%) of 3956 had high-volume metastases, and among those with non-metastatic disease, 1033 (38·4%) were lymph node positive. A PSA concentration of 0·2 ng/mL or less was less frequent at 6 weeks or 12 weeks, but was associated with equivalent survival rates, compared with a PSA of 0·2 ng/mL or less at 24 weeks. Survival rates of PSA subcategories (≤0·2 ng/mL, >0·2 to 1·0 ng/mL, >1·0 to 3·0 ng/mL, and >3·0 ng/mL) differed by metastatic volume or, in patients with non-metastatic disease, by nodal status. Survival was longest for patients allocated to abiraterone with or without enzalutamide. Among patients with metastatic disease in the abiraterone with or without enzalutamide group who had a PSA of 0·2 ng/mL or less at 24 weeks, 96-month overall survival in patients with low-volume metastatic disease (64·1% [95% CI 57·8-69·8]) was higher than in patients with high-volume metastatic disease (44·6% [37·1-51·9]), but lower than in patients with non-metastatic, node-positive disease (79·4% [73·8-83·9]). 96-month overall survival was highest for patients with non-metastatic, node-negative disease (82·8% [95% CI 78·7-86·1]). Metastatic volume or nodal status influence survival rates associated with on-treatment serum PSA categories, including for undetectable PSA. Radiological features and serum PSA could be combined to better predict survival. PSA at 24 weeks showed strongest associations with overall survival, although a PSA concentration of 0·2 ng/mL or less at any timepoint predicted favourable outcome. These findings could inform prognosis and warrant evaluation for treatment selection in clinical trials. Cancer Research UK, Prostate Cancer UK, UK Medical Research Council, and John Black Charitable Foundation.
This study presents a computational QSPR framework for the analysis of protein-associated small molecular graphs by using machine learning under limited sample conditions. Protein related molecules were modeled as molecular graphs, and their structural characteristics were quantified using topological indices, physicochemical properties, and molecular complexity descriptors. To address the high dimensionality relative to the sample size (n = 20), univariate feature selection was employed to retain the most informative descriptors, and model performance was rigorously evaluated using Leave-One-Out Cross-Validation (LOOCV). An Artificial Neural Network (ANN) optimized with the L-BFGS algorithm was benchmarked against Support Vector Regression (SVR) to assess predictive robustness. The results demonstrate excellent predictive accuracy for mass related properties such as molecular weight, while revealing inherent limitations of topological descriptors for complex physicochemical properties including isoelectric point and hydrophobicity. The reporting of cross-validation uncertainty confirms the model stability and mitigates overfitting concerns, establishing the proposed framework as a reliable and interpretable approach for small-sample QSPR modeling with therapeutic relevance.
Perinatal depression and anxiety are major contributors to maternal morbidity, with a disproportionate burden in low- and middle-income countries. In Pakistan, common and modifiable biological risks, including anemia and vitamin D deficiency, may interact with psychosocial factors to influence perinatal mental health. This cohort study enrolled 152 pregnant women from a public hospital in Islamabad; 147 completed baseline assessments (12-32 weeks gestation) and 100 were followed at 6-8 weeks postpartum. Validated Urdu versions of the EPDS, GAD-7, and MSPSS were used alongside hemoglobin and vitamin D assessments at both time points. Longitudinal analyses were conducted using generalized linear mixed models, supplemented by cross-sectional and mediation analyses.Depression was prevalent antenatally (41.5%) and increased postpartum (57.0%), while anxiety declined from 25.2% to 12.0%. Higher hemoglobin was protective against antenatal depression (OR = 0.66) and anxiety (OR = 0.65), but not in longitudinal models. Vitamin D deficiency predicted postnatal depression (OR = 3.15), while sufficiency was associated with remission. Social support showed a strong protective effect (OR = 0.24) and mediated 40% of the hemoglobin-depression association. Baseline symptom severity was the strongest predictor of postpartum outcomes. These findings highlight a substantial burden and point to modifiable nutritional and psychosocial targets for intervention.
Exclusive enteral nutrition (EEN) is an established induction therapy in pediatric Crohn's disease (CD); however, its role in adults remains less well defined. A systematic search was performed through December 2025. Eligible studies included randomized controlled trials (RCTs) and non-randomized studies evaluating EEN in adults (≥ 18 years) with active CD. The primary outcome was clinical remission, defined by validated disease activity indices. Risk of bias was assessed using RoB 2 and the Newcastle-Ottawa Scale. Random-effects models were applied to estimate pooled remission rates and relative risks. Forty studies, comprising 2459 patients, were included. In 23 real-world cohort studies (n = 1269), the pooled clinical remission rate with EEN was 66% (95% CI = 0.60-0.71, I2 = 69.9%, p < 0.0001). In five RCTs (n = 315) comparing corticosteroids with EEN, corticosteroids achieved higher remission rates compared with EEN (RR 0.65, 95% CI = 0.50-0.84; p = 0.0009). In eight RCTs (n = 301), remission rates did not differ significantly between elemental and non-elemental formulations (RR 1.04, 95% CI = 0.88-1.23). Sub-group analyses by protein type and lipid composition showed no differences in efficacy. In two studies, combination therapy with biologics plus EEN was associated with a higher clinical remission compared with biologics alone (RR 0.75; 95% CI = 0.67-0.84; p < 0.0001). Adverse events were generally mild, with poor palatability being most frequent. EEN induces clinical remission in adults with CD. It is less efficacious than corticosteroids to induce clinical remission. The efficacy of EEN is independent of formula composition. Given its favorable safety profile, EEN may represent a therapeutic option in select adult patients. PROSPERO registration number: CRD42023445039.
CO2 conversion to value-added fuels and chemicals under photocatalytic conversion is a sustainable solution towards reducing the increasing carbon emission in the atmosphere as well as aiding in clean energy production. Metal organic frameworks (MOFs), which are comprised of transition-metal nodes and multifunctional organic linkers have been found to be highly promising photocatalysts in CO2 reduction as they have a high surface area, structural, and CO2 adsorption capacity. Their photoresponsive property, caused by the transfer of the ligand-to-metal charge, or metal-oxo cluster excitation permits the effective generation and separation of charge carriers, necessary to drive multi-electron reduction reactions of CO2. This review offers a detailed description of the state-of-the-art MOF-based systems on the photoreduction of CO2 to major products of CH4, CH3OH, HCOOH, and CO. Specific attention is paid to the functionalization of linkers, deposition of metal nanoparticles, heterojunction, and co-catalysts engineering, which have a considerable impact on increasing its activity and selectivity of products. The mechanistic knowledge behind charge transfer, intermediate stabilization, and adsorption phenomena are explained in detail. Besides this, the review demonstrates the prevailing bottlenecks, such as charge recombination, low quantum yields, and poor long-term stability, and how machine learning methods could be used to speed up the prediction and optimization of high-performance MOF photocatalysts. Overall, MOFs still have an enormous potential in solar-based CO2 valorization, but improvements in stability and reactor integration are required before they can be used in practice.
Phylogenetic tree construction from homologous sequences is a fundamental approach for studying evolutionary relationships. However, in cases where sequence similarity is too low to generate reliable alignments, comparison of protein structure provides an alternative means for inferring deep evolutionary relationships. MD-phylogeny is a method that integrates structural comparison with molecular dynamics (MD) simulations to generate robust phylogenies for protein datasets within the twilight zone of sequence similarity. This approach uses well-established structural superposition methods for building trees from structure, with a method for generating structural variants using MD simulations, from which confidence scores analogous to bootstrapping can be derived.This protocol provides a step-by-step guide to performing MD-phylogeny, covering dataset selection, structural comparisons, tree construction, and the generation of statistical support through MD simulations.
Drought has consequences for microbial decomposition rates, including indirect effects through changes in plant litter chemistry. Here, we studied the impact of a decade-long drought on plant litter chemistry and microbial decomposition traits in a semi-arid ecosystem during an 18-month litter bag experiment. We investigated litter sourced from four conditions: grass and shrub vegetation under ambient and reduced precipitation. We hypothesized that litter chemistry drives microbial decomposition capabilities and enzyme activity due to vegetation differences and drought effects on litter chemistry. We found that carbohydrate-rich grass litter had a higher abundance of decomposition genes detected using metagenomics and enzyme activity than more recalcitrant shrub litter, which was richer in lignin and lipids; these patterns were related to substrate supply. Drought decreased some carbohydrate fractions in grass litter but did not change the lignin fraction in grass and shrub litter, suggesting that drought does not make litter more recalcitrant. Most decomposition genes and enzyme activities were not significantly affected by drought, thereby maintaining decomposition rates. Microbial community succession patterns-decreasing fungal abundance and increasing bacterial abundance with time-corresponded with decreasing chitin gene abundance and increasing peptidoglycan gene abundance over time, indicating microbial necromass recycling. We demonstrate minimal litter chemistry-mediated effects of drought but show significant changes in community composition and their decomposition capabilities over time, highlighting that complex microbial-chemical interactions under climate change can influence ecosystem-scale processes. Climate change is causing more severe and frequent droughts in semi-arid ecosystems, affecting soil microbes breaking down plant litter. Our research focuses on understanding the less studied pathway of drought impact on microbes via changes in plant litter chemistry. Drought can alter the plant litter chemistry by changing the composition and physiology of plants, which can alter microbial decomposition and ecosystem-level carbon cycling. We investigated litter decomposition traits of microbial communities in grass and shrub litter under long-term drought. There were significant changes in litter chemistry under drought but no increase in lignin fraction. Despite this, microbial communities maintained their decomposition capabilities under drought, highlighting the ability of microbes to adapt and continue functioning. We also demonstrate unique microbial community succession patterns and dead biomass recycling, which can have implications for carbon cycling rates in the ecosystem. This study sheds light on the complex microbial interactions that affect ecosystem functioning under climate change.
Skin burns are a major health concern that is caused by severe electric shocks, chemical and thermal exposure. The intense skin burns can cause the fibroblast cell death which can lead to the delayed wound healing. Direct ink write (DIW) printing is a promising three-dimensional (3D) printing technology that provides availability of different polymeric solutions and incorporation of bioactive agents within the polymeric blends with low material wastage. Herein, we fabricated a promising combination of ink consisting of sodium alginate (Na-ALG), guar gum (GG), and Ficus carica (FC) for DIW printing. The formulated scaffolds showed favorable rheological properties and layer fidelity. The scaffolds depicted appropriate intercrosslinked porous morphology that supported swelling ability. Na-ALG/GG/FC scaffolds were biodegradable, released gallic acid (GA) and demonstrated antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Scaffold exhibited biocompatibility of 109% on Day 7 with fibroblasts and released vascular endothelial growth factor (VEGF) which indicated formation of new blood vessels. Hence, Na-ALG/GG/FC scaffolds are a potential candidate for treating chronic wounds.
Given the severe morbidity, mortality, and substantial cost of periprosthetic joint infection (PJI), substantial research has been conducted to compare peri- and postoperative infection-prevention strategies. To our knowledge, there are no studies to date that have evaluated the one-year efficacy of intraoperative vancomycin powder and/or dilute povidone-iodine (DPI) lavage versus saline lavage in total joint arthroplasty. We previously reported no significant group differences at three months in a large multicenter randomized controlled trial. The present study reports 1-year outcomes of the same cohort. In this prospective, multicenter trial, 2,053 high-risk patients undergoing primary, unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to one of four intraoperative protocols: vancomycin powder, DPI, VPIP (combination), or saline lavage control. The primary outcome was 1-year PJI resulting in septic revision surgery. Analyses were conducted on a per-protocol basis using Chi-square tests stratified by procedure. At one year, complete follow-up was available for 798 THA and 1,032 TKA patients after accounting for withdrawals, loss to follow-up, and nine unrelated deaths. In the THA cohort, PJI occurred in 0.5% of vancomycin patients, 1.7% of iodine patients, 1.9% of VPIP patients, and 1.1% of saline patients (P = 0.62). In the TKA cohort, PJI occurred in 1.6% of vancomycin patients, none of the iodine patients, 2.0% of VPIP patients, and 0.4% of saline patients (P = 0.05). There were no significant differences between study groups at zero to three months (P = 0.14 for THA, P = 0.13 for TKA), three to 12 months (P = 0.67 for THA, P = 0.80 for TKA), or combined zero to 12 months (P = 0.62 for THA, P = 0.05 for TKA). There were no significant differences in 1-year PJI rates observed across prophylactic strategies in high-risk primary THA or TKA. These findings suggest that intraoperative antiseptic and antibiotic protocols may have limited influence on longer-term outcomes.
Inflammatory myofibroblastic tumors (IMT) are mesenchymal neoplasms of intermediate malignant potential, characterized by recurrent gene fusions in potentially targetable receptor tyrosine kinases. Primary thoracic IMTs are rare, and their molecular landscape remains incompletely characterized. A ten-year retrospective (2014-2024) clinicopathological analysis of primary thoracic IMTs was done. Histomorphological evaluation and molecular characterization by a graded approach incorporating immunohistochemistry, fluorescence-in-situ hybridization, multiplex reverse-transcription polymerase chain reaction, and next-generation targeted panel sequencing were performed for the common implicated driver fusions. Thirty IMTs involving the lung (n=17), tracheobronchial tree (n=12), and pleura (n=1) were identified. Median age at diagnosis was 18 years (range: 2 to 51 years), including 14 paediatric and 16 adult patients. Male: female ratio was 2.2:1 and 1.3:1, in adults and children, respectively. Majority (22/30, 73.3%) showed cellular spindle-cell pattern with lymphoplasmacytic inflammation. None showed significant atypia, necrosis, or mitotic activity. Molecular characterisation achieved in 22/30 cases revealed 73.3% (16/22) ALK-IMTs, 23% (5/22) ROS1-IMTs, and a single NTRK3-IMT. No statistically significant differences were seen among molecular subgroups, although ALK-IMTs were diagnosed at a higher median age (24.5 years) as compared to ROS1-IMTs (15 years). On follow-up (median follow up period: 24 months), local recurrence was observed in 23% (3/13) patients, all harbouring ALK-IMTs, one of whom was successfully treated with ALK inhibitor therapy; no disease-related deaths were recorded. Primary thoracic IMT affects children and young adults. Majority are driven by ALK gene rearrangements, followed by ROS1 alterations, underscoring role of molecular profiling in potential therapeutic stratification.
Coronary artery disease (CAD), peripheral arterial disease (PAD), and ischemic stroke (IS) are the principal manifestations of atherosclerotic cardiovascular diseases (ASCVDs). Here we systematically explored the shared and distinct genetic underpinnings of these ASCVDs. SNP-based heritability estimates were calculated using GCTA-GREML in a subset of the UK Biobank, where 8000 controls and equally sized cases were randomly selected for the three ASCVDs separately. Genetic correlations and causal relations were analyzed among three ASCVDs, 13 risk factors and three comorbid conditions using summary data of respective genome-wide association studies (GWASs). Cross-trait meta-analyses and pathway analyses were conducted to investigate shared and distinct risk loci, as well as pathway activities. Overall, CAD showed the highest SNP-based heritability estimate (23.7 ± 3.3%), which was significantly higher than that of PAD (15.1 ± 2.3%) and IS (9.1 ± 2.8%). Genetic correlations were modest, being largest for CAD-PAD (rg = 0.65), and similar for CAD-IS (rg = 0.47) and PAD-IS (rg = 0.48). Of 233 significant risk loci, 71 (30.5%) were shared by three, and 159 (68.2%) by at least two ASCVDs. Analyses of genetic correlations, Mendelian randomization, and pathway enrichment revealed significant differences between respective ASCVDs. Specially, lipid traits were more strongly associated with CAD and PAD than IS; diabetes mellitus and lifestyle factors affected predominantly PAD, while blood coagulation/clotting pathways and atrial fibrillation were predominantly associated with IS. Interestingly, pathways related to vascular remodeling and inflammation were significantly enriched by genes affecting all ASCVD. The genetic foundation of the three ASCVDs varies substantially, including genetically-mediated effects of associated risk factors and pathways, suggesting commonalities but also differences in the pathogenesis of atherosclerosis in respective arterial beds. Shared genetic features of ASCVDs may be particularly informative for drug target identification.
While previous studies have correlated blastocyst expansion with pregnancy, there is limited evidence regarding post-warming characteristics and specifically the capability of the vitrified and warmed blastocyst to re-expand fully to the pre-vitrification state. This study aimed to examine the effect of blastocyst re-expansion on clinical pregnancy rates (CPRs) in frozen embryo transfer (FET) cycles. In this retrospective cohort, FET patients were stratified into "collapsed" and "re-expanded" groups and further categorized into good (≥ 3BB) or low (<3BB) embryo quality at time of vitrification. Patients were age-matched on a 1:2 ratio for comparison between the collapsed (n=165) and re-expanded (n=330) groups. The primary outcome of clinical pregnancy rate (CPR), in addition to secondary pregnancy outcomes, was reported. Chi-square tests of independence and Cramer's V test were performed to examine the association between CPR of collapsed versus re-expanded blastocysts; embryo quality; and age (< 38 years vs ≥ 38 years). Odds ratios with 95% confidence intervals were reported. A total of 5,996 patients underwent frozen embryo transfer (FET) between 2005 and 2012, of whom 165 (2.8%) received a collapsed blastocyst. Patients were age-matched in a 1:2 ratio in comparison to patients who implanted a re-expanded blastocyst (n = 330). Clinical pregnancy rate (CPR) was 28.5% in the re-expanded group compared with 15.8% in the collapsed group (OR = 2.145, 95% CI [1.324, 3.473]). There was a significant association between CPR and blastocyst expansion, χ²(1, N = 496) = 9.901, p = .002, with a small effect size (V = 0.14). CPR was also significantly associated with embryo quality (p = .017) and age (p < .001), regardless of embryo expansion. Our findings suggest that the transfer of a collapsed blastocyst during FET is associated with a lower CPR than a re-expanded blastocyst. Despite these differences, a viable pregnancy can be achieved after the transfer of a collapsed blastocyst, especially in younger patients with good quality embryos at the time of vitrification.
Preeclampsia remains a major cause of maternal and fetal morbidity worldwide, originating from abnormal placental development and reduced perfusion. Conventional Doppler indices, although widely used, are limited in sensitivity, reproducibility, and early detection. Advances in three-dimensional power Doppler ultrasound (3D PD-US) and its vascular indices - vascularization index (VI), flow index (FI), and vascular FI (VFI) - offer semiquantitative evaluation of intraplacental microvascular function. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines, this structured narrative synthesis reviewed literature from PubMed, Scopus, and EMBASE (2000-July 2025). A total of 1174 records were identified; after removing 328 duplicates, 846 titles and abstracts were screened, 137 full-text articles were assessed for eligibility, and 74 studies were included in the final synthesis assessing Doppler-based perfusion, biomarkers, or artificial intelligence (AI) integration in preeclampsia. Findings consistently demonstrate reduced VI, FI, and VFI in affected pregnancies, with FI showing the strongest reproducibility across cohorts. Emerging AI models trained on voxel-level Doppler data and angiogenic biomarkers such as placental growth factor and soluble fms-like tyrosine kinase-1 achieved high predictive accuracies (area under the curve 0.85-0.91) for early disease risk, although external validation remains limited. Integration of 3D PD-US indices with AI and biomarkers may enable early risk stratification, personalized monitoring, and informed timing of intervention. Heterogeneity in imaging protocols and the absence of meta-analytic pooling remain key limitations. Placental perfusion, re-envisioned through advanced imaging and AI analytics, emerges as a cornerstone biomarker for anticipatory, precision-based obstetric care.
Human adenoviruses (HAdVs) may cause and are responsible for a broad range of pediatric illnesses. Although several cases are self-limiting, certain children may develop complications requiring pediatric intensive care (PICU). To address the role of HAdVs in children, we aimed to characterize the 10-year clinical spectrum of pediatric HAdVs infections and to identify factors associated with hospitalization and severe disease. This retrospective observational cohort study analyzed the clinical course of children (< 18 years) with laboratory-confirmed HAdV infection episodes treated at a tertiary pediatric center between 2014 and 2024. Demographic features, comorbidities, laboratory results, respiratory support requirements, PICU, and clinical outcomes were collected. The severe outcome was defined as a composite endpoint including PICU admission, invasive mechanical ventilation, and/or 30-day mortality. A total of 877 HAdV infection episodes were included, whereas 276 (31.5%) of the patients were hospitalized. Among hospitalized patients, 32.2% required respiratory support, 18.8% required PICU care, and the 30-day mortality was 2.5%. Overall, 104 children (11.9%) developed severe disease. Underlying medical conditions were significantly more frequent among children with severe disease, while those without underlying disease were more common in the non-severe group (69.8% vs. 22.1%; p < 0.001). Viral coinfections were detected in 35.8% of patients but were not associated with increased hospitalization or severity. In multivariable analysis, male sex (OR 2.30, 95% CI 1.23-4.29; p = 0.009), neurologic disease (OR 2.12, 95% CI 1.01-4.42; p = 0.045), cardiac disease (OR 3.27, 95% CI 1.49-7.17; p = 0.003), and hematopoietic stem cell transplantation (HSCT) (OR 4.32, 95% CI 1.36-13.7; p = 0.013) were independently associated with severe outcome.Conclusion: Human adenovirus infection represents a notable clinical burden in children, with a considerable proportion requiring hospitalization and developing severe disease. Underlying neurologic and cardiac diseases, as well as HSCT, were key risk factors for severe outcome, whereas viral coinfections were common but not associated with worse clinical outcome.
Although Doxorubicin (Dox) is an effective anticancer drug, it can cause severe cardiotoxicity. While several mechanisms have been proposed to explain Dox-induced cardiomyopathy (DIC), strategies to prevent it remain limited. In previous research on isolated cardiomyocytes, we identified that Empagliflozin (EMPA), an antidiabetic drug, mitigated Dox-induced ER stress and apoptosis. In this in vivo study using rats, we further investigated EMPA's potential in preventing and treating DIC. Rats administered a cumulative dose of 15 mg/kg Dox exhibited significant cardiovascular damage, including left ventricular cavity dilation, decreased left ventricular ejection fraction (LVEF), ER dilation, mitochondrial defects and vacuole formation. These structural changes were linked to the activation of ER-stress pathways (PERK, IRE1 and ATF6) and upregulation of apoptotic proteins initiated by ER stress. When EMPA (10 mg/kg/day) was administered either prophylactically or concurrently with Dox, it significantly attenuated adverse LV remodelling and preserved LVEF. Additionally, EMPA prevented ER stress and subsequent apoptosis in the myocardium of the Dox + EMPA-treated group. These findings suggest that EMPA offers cardioprotective benefits in DIC, likely through the inhibition of ER-stress-induced myocardial injury.
The present study evaluated the biocontrol potential of soilborne Bacillus strains isolated from the largely unexplored soils of Khyber Pakhtunkhwa, Pakistan, against two globally significant lepidopteran pests, the white-marked tussock moth (Orgyia leucostigma) and the wax moth (Galleria mellonella). Among the isolates screened, Bacillus subtilis F1 exhibited high insecticidal activity, causing 74-77% mortality of larvae within 48 h when treated with whole-cell suspensions. In comparison, treatment with cell-free culture metabolites resulted in moderate mortality (20-23%), indicating that the primary insecticidal effect is largely cell-mediated, with extracellular metabolites contributing a secondary role. While the specific compounds responsible for the metabolite activity were not characterized in this study, previous reports suggested that Bacillus spp. may secrete proteins, enzymes, or secondary metabolites with insecticidal properties, which could explain the observed larval mortality. These findings demonstrated that infection, colonization, or combined cell-associated factors play a major role in larval mortality. To our knowledge, this is the first report of dual larvicidal activity of an indigenous B. subtilis strain against both O. leucostigma and G. mellonella. The present study also highlighted the presence of promising biocontrol agents in underexplored soil ecosystems, supporting their potential application in sustainable insect pest management. The online version contains supplementary material available at 10.1007/s13205-026-04779-y.
Background Effective deep brain stimulation (DBS) requires precise visualisation of the target on magnetic resonance imaging (MRI). However, on clinical 3 Tesla (T) MRI these targets are often imperfectly delineated, introducing potential error. Higher magnetic field strength e.g. 7T MRI ought to improve visualisation via resolution or contrast. Our aim was to appraise current evidence for proposed improvements with 7T MRI for DBS implantation. Specifically, we wanted to consider evidence for improvements in target visualisation, the imaging sequences that can leverage improvements, and how better MRI quality translated into clinical outcomes. Methods A scoping review was performed across multiple databases (PubMed and EMBASE). Search criteria included the terms ('7 Tesla' OR '7T') AND ('deep brain stimulation' OR 'thalamus' OR 'basal ganglia' OR 'globus pallidus' OR 'zona incerta' OR 'pedunculopontine' OR 'subthalamic nucleus'). Studies were selected based on target visualisation, sequence appraisal, or clinical application. Quantitative data were extracted for meta-analysis. Results 66 papers were identified. Target visualisation was improved with better signal- and contrast-to-noise ratio compared to 1.5T or 3T MRI, while manual segmentations of the subthalamic nucleus at 7T showed high inter-rater reliability (Dice = 0.75, 10 studies). Gradient echo sequences and quantitative susceptibility mapping offered the best demarcation and tissue contrast of basal ganglia structures. Clinical studies have demonstrating promising results with novel targets and targeting strategies, but not when simply implementing 7T MRI data in existing targeting approaches. Conclusions 7T MRI offers objectively better data quality that translates to better delineation of DBS targets. However, to translate these benefits into improved clinical outcomes will require a development of DBS planning and targeting approaches rather than just utilising current practices. In the future, there is significant potential for establishing larger multi-centre series, exploring new sequences, and developing novel clinical trials to test for improvements in patient outcomes.
Background: Alcohol-induced hypertension (HTN) is linked to a 2.3-fold increase in cardiovascular-related death.Objective: We aimed to identify temporal trends in alcohol-induced HTN mortality among United States (US) adults stratified by year, sex, age, race, and region.Methods: Data on alcohol-induced HTN mortality among adults (≥25 years) in the US from 1999 to 2020 were extracted from the CDC WONDER database, utilizing ICD-10 codes. Crude (CMRs) and age-adjusted mortality rates (AAMRs) were calculated. Temporal trends in AAMRs were assessed using Joinpoint regression. Mortality forecasts through 2030 were generated using the ARIMA model in STATA software (version 17.0).Results: From 1999 to 2020, 50,793 alcohol-induced HTN-related deaths were recorded in the US, with an overall AAMR of 0.858 per 100,000. The AAMR increased from 0.279 (95% CI: 0.257-0.302) in 1999 to 1.348 (95% CI: 1.305-1.390) in 2018, rising further to 2.014 (95% CI: 1.963-2.066) in 2020. Mortality was higher in males (AAMR 2.16) than in females (0.55). The highest burden occurred among American Indians/Alaska Natives (AAMR 2.392), while the lowest was observed in Asians/Pacific Islanders (0.206). The Western region had the highest AAMR (1.116). CMR peaked among individuals aged 55-64 years (2.416), with slightly higher rates in rural areas. Forecast analysis projected the overall AAMR to increase from 2.01 in 2020 to 4.18 by 2030.Conclusion: Rising mortality from alcohol-induced HTN highlights an urgent need for strengthened control policies for alcohol use, early identification of hazardous drinking, and integrated management of hypertension and alcohol use to reduce preventable cardiovascular mortality in the US.