Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.

PURPOSE: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC. METHODS: The AVENGER 500 trial (ClinicalTrials.gov identifier: NCT03504423) is a global, randomized phase III trial conducted at 74 sites across six countries to investigate the efficacy and safety of devimistat in combination with mFFX (experimental arm) compared with standard-dose FFX (control arm) in treatment-naïve patients with mPC. Treatment, administered in once-every-2-weeks cycles until disease progression or intolerable toxicity, included intravenous devimistat at 500 mg/m2 total per day on days 1 and 3 in the experimental arm. The primary end point of the study was overall survival (OS). RESULTS: Five hundred and twenty-eight patients were randomly assigned (266 in the experimental arm and 262 in the control arm). The median OS was 11.10 months for devimistat plus mFFX versus 11.73 months for FFX (hazard ratio [HR], 0.95 [95% CI, 0.77 to 1.18]; P = .655) and median progression-free survival was 7.8 months versus 8.0 months, respectively (HR, 0.99 [95% CI, 0.76 to 1.29]; P = .94). Grade ≥3 treatment-emergent adverse events with >10% frequency in the devimistat plus mFFX arm versus the FFX arm were neutropenia (29.0% v 34.5%), diarrhea (11.2% v 19.6%), hypokalemia (13.1% v 14.9%), anemia (13.9% v 13.6%), thrombocytopenia (11.6% v 13.6%), and fatigue (10.8% v 11.5%), respectively. CONCLUSION: Devimistat in combination with mFFX did not improve long- and short-term mPC patient outcomes compared with standard FFX. There were no new toxicity signals with the addition of devimistat.

Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature.

Breast cancer remains a significant health challenge with complex molecular mechanisms. While many studies have explored genetic markers in breast carcinogenesis, few have studied the potential impact of pharmacological interventions such as Atorvastatin on its genetic landscape. This study aimed to elucidate the molecular distinctions between normal and tumor-adjacent tissues in breast cancer and to investigate the potential protective role of atorvastatin, primarily known for its lipid-lowering effects, against breast cancer. Searching the Gene Expression Omnibus database identified two datasets, GSE9574 and GSE20437, comparing normal breast tissues with tumor-adjacent samples, which were merged, and one dataset, GSE63427, comparing paired pre- and post-treated patients with atorvastatin. Post-ComBat application showed merged datasets' consistency, revealing 116 DEGs between normal and tumor-adjacent tissues. Although initial GSE63427 data analysis suggested a minimal impact of atorvastatin, 105 DEGs post-treatment were discovered. Thirteen genes emerged as key players, both affected by Atorvastatin and dysregulated in tumor-adjacent tissues. Pathway analysis spotlighted the significance of these genes in processes like inflammation, oxidative stress, apoptosis, and cell cycle control. Moreover, there was a noticeable interaction between these genes and the immunological microenvironment in tumor-adjacent tissues, with Atorvastatin potentially altering the suppressive immune landscape to favor anti-tumor immunity. Survival analysis further highlighted the prognostic potential of the 13-gene panel, with 12 genes associated with improved survival outcomes. The 13-gene signature offers promising insights into breast cancer's molecular mechanisms and atorvastatin's potential therapeutic role. The preliminary findings advocate for an in-depth exploration of atorvastatin's impact on.

Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database.

BACKGROUND: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging. OBJECTIVE: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. METHODS: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. RESULTS: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/. CONCLUSION: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

Methods for Bioinformatic Prediction of Genuine sRNAs from Outer Membrane Vesicles.

The molecular pathogenesis of Gram-negative bacteria remains a complex and incompletely understood phenomenon. Various factors are believed to contribute to the pathogenicity of these bacteria. One key mechanism utilized by Gram-negative bacteria is the production of outer membrane vesicles (OMVs), which are small spherical particles derived from the bacterial outer membrane. These OMVs are crucial in delivering virulence factors to the host, facilitating host-pathogen interactions. Within these OMVs, small regulatory RNAs (sRNAs) have been identified as important players in modulating the host immune response. One of the main challenges in studying OMVs and their cargo of sRNAs is the difficulty in isolating and purifying sufficient quantities of OMVs, as well as accurately predicting genuine sRNAs computationally. In this chapter, we present protocols aimed at overcoming these obstacles.

Femoral versus radial access for middle meningeal artery embolization for chronic subdural hematomas: multicenter propensity score matched study.

BACKGROUND: With transradial access (TRA) being more progressively used in neuroendovascular procedures, we compared TRA with transfemoral access (TFA) in middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH). METHODS: Consecutive patients undergoing MMAE for cSDH at 14 North American centers (2018-23) were included. TRA and TFA groups were compared using propensity score matching (PSM) controlling for: age, sex, concurrent surgery, previous surgery, hematoma thickness and side, midline shift, and pretreatment antithrombotics. The primary outcome was access site and overall complications, and procedure duration; secondary endpoints were surgical rescue, radiographic improvement, and technical success and length of stay. RESULTS: 872 patients (median age 73 years, 72.9% men) underwent 1070 MMAE procedures (54% TFA vs 46% TRA). Access site hematoma occurred in three TFA cases (0.5%; none required operative intervention) versus 0% in TRA (P=0.23), and radial-to-femoral conversion occurred in 1% of TRA cases. TRA was more used in right sided cSDH (58.4% vs 44.8%; P<0.001). Particle embolics were significantly higher in TFA while Onyx was higher in TRA (P<0.001). Following PSM, 150 matched pairs were generated. Particles were more utilized in the TFA group (53% vs 29.7%) and Onyx was more utilized in the TRA group (56.1% vs 31.5%) (P=0.001). Procedural duration was longer in the TRA group (median 68.5 min (IQR 43.1-95) vs 59 (42-84); P=0.038), and radiographic success was higher in the TFA group (87.3% vs 77.4%; P=0.036). No differences were noted in surgical rescue (8.4% vs 10.1%, P=0.35) or technical failures (2.4% vs 2%; P=0.67) between TFA and TRA. Sensitivity analysis in the standalone MMAE retained all associations but differences in procedural duration. CONCLUSIONS: In this study, TRA offered comparable outcomes to TFA in MMAE for cSDH in terms of access related and overall complications, technical feasibility, and functional outcomes. Procedural duration was slightly longer in the TRA group, and radiographic success was higher in the TFA group, with no differences in surgical rescue rates.

Predictors of Aneurysm Obliteration in Patients Treated with the WEB Device: Results of a Multicenter Retrospective Study.

BACKGROUND AND PURPOSE: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment. MATERIALS AND METHODS: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up. RESULTS: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis was observed in 485/537 (90.3%) of nonoccluded aneurysms. At the final follow-up, complete occlusion was achieved in 497/763 (65.1%) patients, and retreatment was required for 56/763 (7.3%) patients. On multivariable analysis, history of smoking, maximal aneurysm diameter, and the presence of an aneurysm wall branch were negative predictors of complete occlusion (OR, 0.5, 0.8, and 0.4, respectively). Maximal aneurysm diameter, the presence of an aneurysm wall branch, posterior circulation location, and male sex increase the chances of retreatment (OR, 1.2, 3.8, 3.0, and 2.3 respectively). Intraprocedural occlusion resulted in a 3-fold increase in the long-term occlusion rate and a 5-fold decrease in the retreatment rate (P < .001), offering a specificity of 87% and a positive predictive value of 85% for long-term occlusion. CONCLUSIONS: Intraprocedural occlusion can be used to predict the chance of long-term aneurysm occlusion and the need for retreatment after embolization with a WEB device. Smoking, aneurysm size, and the presence of an aneurysm wall branch are associated with decreased chances of successful treatment.

Epidemiological, and molecular investigation of Canine parvovirus-2 infection in Egypt.

IMPORTANCE: Canine parvovirus enteritis (CPE) is a contagious viral disease of dogs caused by the canine parvovirus-2 (CPV-2) associated with high morbidity and mortality rates. CPV-2 has a high global evolutionary rate. Molecular characterization of CPV-2 and understanding its epidemiology are essential for controlling CPV-2 infections. OBJECTIVE: This study examined the risk factors and survival outcomes of dogs infected with CPV-2. Molecular characterization of CPV-2 genotypes circulating in Egypt was performed to determine the evolution of CPV-2 nationally and globally. METHODS: An age-matched case-control study was conducted on 47 control and 47 CPV-infected dogs. Conditional logistic regression analysis examined the association between the potential risk factors and CPE in dogs. Survival analysis was performed to determine the survival pattern of the infected dogs. Thirteen fecal samples from infected dogs were collected to confirm the CPV genotype by CPV-2 VP2 gene sequencing, assembly of nucleotide sequences, and phylogenic analysis. RESULTS: Unvaccinated and roamer dogs had eight and 2.3 times higher risks of CPV infection than vaccinated dogs and non-roamer dogs, respectively. The risk of death from CPE was high among dogs without routine visits to veterinary clinics and among non-roamer dogs. Molecular characterization of CPV-2 confirmed its genotype identity and relationship with the CPV-2 c and b clade types. CONCLUSIONS AND RELEVANCE: This study highlights the potential factors for CPE control, especially vaccination and preventing dogs from roaming freely outside houses. Isolated CPV genotypes are closely related to southern Asian genotypes, suggesting a substantial opportunity for global transmission.

Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis.

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.

The Era of Radial-Specific Catheters: A Multicenter Comparison of the Armadillo and RIST Catheters in Transradial Procedures.

BACKGROUND AND OBJECTIVES: As the radial approach is gaining popularity in neurointervention, new radial-specific catheters are being manufactured while taking into consideration the smaller size of the radial artery, different trajectories of angles into the great vessels from the arm, and subsequent force vectors. We compared outcomes of transradial procedures performed using the Armadillo catheter (Q'Apel Medical Inc.) and the RIST radial guide catheter (Medtronic). METHODS: This is a retrospective multicenter study comparing outcomes of transradial neuroendovascular procedures using the Armadillo and RIST catheters at 2 institutions between 2021 and 2024. RESULTS: The study comprised 206 patients, 96 of whom underwent procedures using the Armadillo and 110 using the RIST. Age and sex were comparable across cohorts. In most procedures, 1 target vessel was catheterized (Armadillo: 94.8% vs 89.1%, P = .29) with no significant difference between cohorts. The use of an intermediate catheter was minimal in both cohorts (Armadillo 5.2% vs RIST: 2.7%, P = .36), and the median number of major vessel catheterization did not significantly differ between cohorts (Armadillo: 1 [1-4] vs RIST: 1 [0-6], P = .21). Failure to catheterize the target vessel was encountered in 1 case in each cohort (Armadillo: 1.0% vs RIST: 0.9%, P = .18), and the rate did not significantly differ between cohorts. Similarly, the rate of conversion to femoral access was comparable between cohorts (Armadillo: 2.1% vs RIST: 1.8%, P = .55). There was no significant difference in access site complications (Armadillo: 1% vs RIST: 2.8%, P = .55) or neurological complications (Armadillo: 3.1% vs RIST: 5.5%, P = .42) between cohorts. CONCLUSION: No significant difference in successful catheterization of target vessels, procedure duration, triaxial system use, complication rates, or the need for transfemoral cross-over was observed between both catheters. Both devices offer high and comparable rates of technical success and low morbidity rates.

A non-invasive AI-based system for precise grading of anosmia in COVID-19 using neuroimaging.

COVID-19 (Coronavirus), an acute respiratory disorder, is caused by SARS-CoV-2 (coronavirus severe acute respiratory syndrome). The high prevalence of COVID-19 infection has drawn attention to a frequent illness symptom: olfactory and gustatory dysfunction. The primary purpose of this manuscript is to create a Computer-Assisted Diagnostic (CAD) system to determine whether a COVID-19 patient has normal, mild, or severe anosmia. To achieve this goal, we used fluid-attenuated inversion recovery (FLAIR) Magnetic Resonance Imaging (FLAIR-MRI) and Diffusion Tensor Imaging (DTI) to extract the appearance, morphological, and diffusivity markers from the olfactory nerve. The proposed system begins with the identification of the olfactory nerve, which is performed by a skilled expert or radiologist. It then proceeds to carry out the subsequent primary steps: (i) extract appearance markers (i.e., 1 s t and 2 n d order markers), morphology/shape markers (i.e., spherical harmonics), and diffusivity markers (i.e., Fractional Anisotropy (FA) & Mean Diffusivity (MD)), (ii) apply markers fusion based on the integrated markers, and (iii) determine the decision and corresponding performance metrics based on the most-promising classifier. The current study is unusual in that it ensemble bags the learned and fine-tuned ML classifiers and diagnoses olfactory bulb (OB) anosmia using majority voting. In the 5-fold approach, it achieved an accuracy of 94.1%, a balanced accuracy (BAC) of 92.18%, precision of 91.6%, recall of 90.61%, specificity of 93.75%, F1 score of 89.82%, and Intersection over Union (IoU) of 82.62%. In the 10-fold approach, stacking continued to demonstrate impressive results with an accuracy of 94.43%, BAC of 93.0%, precision of 92.03%, recall of 91.39%, specificity of 94.61%, F1 score of 91.23%, and IoU of 84.56%. In the leave-one-subject-out (LOSO) approach, the model continues to exhibit notable outcomes, achieving an accuracy of 91.6%, BAC of 90.27%, precision of 88.55%, recall of 87.96%, specificity of 92.59%, F1 score of 87.94%, and IoU of 78.69%. These results indicate that stacking and majority voting are crucial components of the CAD system, contributing significantly to the overall performance improvements. The proposed technology can help doctors assess which patients need more intensive clinical care.

Characterisation of sRNAs enriched in outer membrane vesicles of pathogenic Flavobacterium psychrophilum causing Bacterial Cold Water Disease in rainbow trout.

Flavobacterium psychrophilum (Fp) causes Bacterial Cold Water Disease in salmonids. During host-pathogen interactions, gram-negative bacteria, such as Fp, release external membrane vesicles (OMVs) harbouring cargos, such as DNA, RNA and virulence factors. This study aimed to characterise the potential role of the OMVs' small RNAs (sRNAs) in the Fp-rainbow trout host-pathogen interactions. sRNAs carried within OMVs were isolated from Fp. RNA-Seq datasets from whole-cell Fp and their isolated OMVs indicated substantial enrichment of specific sRNAs in the OMVs compared to the parent cell. Many of the OMV-packaged sRNAs were located in the pathogenicity islands of Fp. Conservation of sRNAs in 65 strains with variable degrees of virulence was reported. Dual RNA-Seq of host and pathogen transcriptomes on day 5 post-infection of Fp -resistant and -susceptible rainbow trout genetic lines revealed correlated expression of OMV-packaged sRNAs and their predicted host's immune gene targets. In vitro, treatment of the rainbow trout epithelial cell line RTgill-W1 with OMVs showed signs of cytotoxicity accompanied by dynamic changes in the expression of host genes when profiled 24 h following treatment. The OMV-treated cells, similar to the Fp -resistant fish, showed downregulated expression of the suppressor of cytokine signalling 1 (SOCS1) gene, suggesting induction of phagosomal maturation. Other signs of modulating the host gene expression following OMV-treatment include favouring elements from the phagocytic, endocytic and antigen presentation pathways in addition to HSP70, HSP90 and cochaperone proteins, which provide evidence for a potential role of OMVs in boosting the host immune response. In conclusion, the study identified novel microbial targets and inherent characteristics of OMVs that could open up new avenues of treatment and prevention of fish infections.

Predictors of methotrexate adherence and patient's awareness of it in rheumatoid arthritis and its effect on quality of life.

Introduction: Adherence studies among rheumatoid arthritis (RA) patients, in Egypt and throughout the Middle East region, are lacking. This study aimed to evaluate methotrexate (MTX) adherence in Rheumatoid arthritis (RA) patients and to identify specific non-adherence predictors. Methods: A cross-sectional observational study included 300 RA patients who were administered MTX for at least one year. The survey was completed through direct interviews. The demographic patient data were collected (age, education, sex, work status, disease duration, duration of MTX administration and current dose). Patients' adherence to MTX predictors for non-adherence, MTX side effects and functional disability were assessed in the study. Results: Majority of respondents showed good MTX adherence, and more than 50% of patient's experienced MTX side effects. A large percentage of participants showed low knowledge about MTX nature and side effects. Most participants reported no or some difficulty in quality of life-related activities and functional disability. Conclusion: MTX adherence and awareness were positively correlated to many variables, including, age, educational level and disease duration, which in turn has its positive impact on the patient's quality of life. Still, more research is needed to determine the impact of non-adherence on the patient's health outcomes.

Off-Label use of Woven EndoBridge device for intracranial brain aneurysm treatment: Modeling of occlusion outcome.

INTRODUCTION: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes. METHODS: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95 % confidence intervals (CI) were reported. RESULTS: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95 % CI 1.25-2.82), larger neck diameter (OR 1.69, 95 % CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95 % CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors. CONCLUSION: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed.

Evaluation of the expression of fibrosis-related genes as non-invasive diagnostic biomarkers for cirrhotic HCV-infected patients.

Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects' PBMCs, and the serum level of TGFß2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFß1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-ß2 transcript and elevated levels of the TGF-ß2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFß1, TGIF1 transcripts, and TGFß2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-ß1, and TGF-ß2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-ß and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.

Sex-based disparities in ascending aortic aneurysm surgery outcomes: a comprehensive analysis of 1148 consecutive patients with propensity-score matching.

BACKGROUND: Women undergoing cardiac surgery have been historically recognized to carry higher periprocedural mortality risk. We aimed to investigate the influence of sex on clinical presentation, perioperative, and long-term outcomes in patients who undergo surgery for ascending aortic aneurysm. METHODS: We conducted a retrospective review of 1148 consecutive patients (380 [33.1%] female) who underwent thoracic aortic surgery under moderate hypothermic circulatory arrest for ascending aortic aneurysms between 2001 and 2021. Baseline and operative characteristics, in-hospital mortality, and survival were compared between male and female patients before and after propensity-score-matched (PSM) analysis. RESULTS: Women were significantly older (median age: 69 [IQR: 63-75] vs. 67 [IQR: 58-73]; P < 0.001), while men had a higher prevalence of aortic valve stenosis, bicuspid valve and coronary artery disease at the time of surgery (P < 0.05). After PSM, EuroSCORE II (4.36 [2.68; 6.87] vs. 3.22 [1.85; 5.31]; p < 0.001), and indexed aortic diameter were significantly higher in female patients (2.94 [2.68; 3.30] vs. 2.58 [2.38; 2.81] cm/m2, p < 0.001). In the matched cohort, men were more likely to experience postoperative delirium (18.1% vs. 11.5%; P = 0.002), and postoperative neurological deficits (6.7% vs. 3.0%, P = 0.044),. Female patients were more likely to receive postoperative packed red blood cells (p = 0.036) and fresh frozen plasma (p = 0.049). In-hospital and 30-day mortality was similar between both groups. Long-term survival was comparable between both groups with 88% vs. 88% at 5 years, 76% vs. 71% at 10 years, and 59% vs. 47% at 15 years. CONCLUSION: Female patients required more transfusions, while males had a higher incidence of postoperative delirium and neurological deficits. Differences in preoperative age and timing of surgery between the sexes could be attributed to variations in comorbidity profiles and the greater prevalence of concomitant surgery indications in males.

Application of edible nanocomposites from chitosan/fenugreek seed mucilage/selenium nanoparticles for protecting lemon from green mold.

Green (Penicillium digitatum) mold can severely endanger the citrus fruits production and quality. Targeting the protection of lemon fruits from green mold infestations with nanobiotechnology approach, the fenugreek seed mucilage (FM) was extracted and exploited for biosynthesis of selenium (SeNPs) nanoparticles; their nanocomposites (NCs) with chitosan (CT) was constructed and employed as antifungal materials and edible coating (ECs) to protect lemon fruits against green mold. The nanoparticles formation and conjugations were verified by infrared (FTIR) analysis and electron microscopy. The FM-synthesized SeNPs had particles average of 8.35 nm, were the NCs of them with CT had size mean of 49.33 nm and charged with +22.8 mV. The CT/FM/SeNPs composite exhibited superior antifungal actions toward P. digitatum isolates, up to 32.2 mm inhibition diameter and 12.5 mg/mL inhibitory concentration, which exceeded the actions of imazilil. The microscopic screening of exposed P. digitatum to NCs clarified their mycelial destructive action within 30 h. The coating of infected lemons with fabricated NCs led to complete elimination of green mold development after 10 days of coating, without any infestation remarks. The innovative fabrication of NCs from CT/FM/SeNPs is strongly suggested to protect citrus crops from green mold and preserve fruits quality.

New prospective insecticidal agents based on thiazolo[4,5-b]quinoxaline derivatives against cotton leafworm Spodoptera litura (Fabricius): Design, synthesis, toxicological, morphology, histological, and biomedical studies.

In this study, a new series of thiazolo[4,5-b]quinoxaline derivatives 3-8 were synthesized by treating 2,3-dichloroquinoxaline with thiosemicarbazone and thiourea derivatives under reflux conditions. The chemical structure of the newly designed derivatives was conducted using spectroscopic techniques. The insecticidal bioassay of the designed derivatives was evaluated against the 2nd and 4th larvae of S. litura after five days as toxicity agents via median lethal concentration (LC50) and the lethal time values (LT50). The results indicated that all the tested compounds had insecticidal effects against both instar larvae of S. litura with variable values. Among them, thiazolo[4,5-b]quinoxaline derivative 3 was the most toxic, with LC50 = 261.88 and 433.68 ppm against 2nd and 4th instar larvae, respectively. Moreover, the thiazolo[4,5-b]quinoxaline derivative 3 required the least time to kill the 50% population (LT50) of 2nd larvae were 20.88, 13.2, and 15.84 hs with 625, 1250, and 2500 ppm, respectively, while for the 4th larval instar were 2.75, 2.08, and 1.76 days with concentrations of 625, 1250, and 2500 ppm, respectively. Larvae's morphological and histological studies for the most active derivative 3 were investigated. According to SEM analysis, the exterior morphology of the cuticle and head capsule was affected. In addition, there were some histological alterations in the cuticle layers and the midgut tissues. Columnar cells began breaking down, and vacuolization occurred in the peritrophic membrane. Moreover, treating 4th S litura larvae hemolymph with compound 3 showed significant changes in biochemical analysis, such as total proteins, GPT, GOT, acetylcholinesterase (AChE), and alkaline phosphatase (AlP). Finally, the toxicity prediction of the most active derivative revealed non-corrosive, non-irritant to the eye, non-respiratory toxicity, non-sensitivity to the skin, non-hepatotoxic, and don't have toxicity on minnow toxicity and T. pyriformis indicating a good toxicity profile for human.

Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α-glucosidase, α-amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation.

A new series of quinoxaline-sulfonamide derivatives 3-12 were synthesized using fragment-based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline-sulfonamide derivatives were evaluated for antidiabetic and anti-Alzheimer's potential against α-glucosidase, α-amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against α-amylase and α-glucosidase with inhibitory percentages between 24.34 ± 0.01%-63.09 ± 0.02% and 28.95 ± 0.04%-75.36 ± 0.01%, respectively. Surprisingly, bis-sulfonamide quinoxaline derivative 4 revealed the most potent activity with inhibitory percentages of 75.36 ± 0.01% and 63.09 ± 0.02% against α-glucosidase and α-amylase compared to acarbose (IP = 57.79 ± 0.01% and 67.33 ± 0.01%), respectively. Moreover, the quinoxaline derivative 3 exhibited potency as α-glucosidase and α-amylase inhibitory with a minute decline from compound 4 and acarbose with inhibitory percentages of 44.93 ± 0.01% and 38.95 ± 0.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide-quinoxaline derivative 3 emerged as the most active member with inhibitory percentage of 41.92 ± 0.02% compared with donepezil (IP = 67.27 ± 0.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

Ruptured Anterior Inferior Cerebellar Artery Aneurysm From a Persistent Trigeminal Artery: A Case Report.

Persistent trigeminal artery (PTA) is the most common remnant of the primitive carotid-vertebrobasilar anastomoses, which typically form and obliterate during the early stages of human embryonic development. While PTA can be non-pathologic and is usually an incidental finding, it is also associated with various other vascular abnormalities, such as arteriovenous malformations and fistulae, but most commonly cerebral aneurysms. In these cases, aneurysms are usually reported in the anterior cerebral circulation or in the PTA trunk itself; to date, only one report exists of an associated aneurysm in the posterior circulation (basilar artery). These associated vascular pathologies are not only a source of morbidity and mortality but can also complicate subsequent endovascular treatment due to different flow patterns and increased vessel tortuosity. In this case report, we present the first reported case of PTA-associated aneurysm in the anterior inferior cerebellar artery and its resulting impact on the endovascular treatment of this aneurysm.