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.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Impact analysis of primary and secondary research in radiology journals.

INTRODUCTION: Primary and secondary studies are considered the two major research categories. In this study, we examined the scientific and social media impact of primary and secondary publication types in papers published radiological journals during 2010-2020. MATERIALS AND METHODS: PubMed publication type tags were used to filter original articles and systematic review and meta-analysis (SR/MA) articles. Clarivate Web of Science was utilized to obtain a list of all radiology journals from the category "Radiology, Nuclear Medicine and Imaging" in Science Citation Index Expanded (SCIE). Automated approach was developed for programmatic extraction of bibliometric and Altmetric yearly citations of each included article using Dimensions API and Altmetric API with Python. Statistical analysis was performed to compare the citation rates between primary and secondary research articles. RESULTS: A total of 96,684 published articles from 2010 to 2020 were identified and their meta-data collected. The mean 2-year citation count following publication year was 5.8 for primary research and 10.2 for SR/MA articles (p < 0.001). Between 2010 and 2020, the mean number of citations per SR/MA article was 51.3 compared to 30.5 per primary research article (p < 0.001). Mean Altmetric score was 8.2 in SR/MA compared to 3.7 for primary research articles (p < 0.001). CONCLUSION: Secondary research studies have been increasing in impact in both academia and social media compared to primary research. Our results highlight the importance and impact of systematic reviews and meta-analysis articles as a scientifically influential study type in radiology.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

Region-specific interobserver agreement of the Alberta Stroke Program Early Computed Tomography Score: A meta-analysis.

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a widely used scoring system for evaluating ischemic stroke to determine therapeutic strategy. However, there is variation in the interobserver agreement of ASPECTS. This systematic review and meta-analysis aimed to investigate the interobserver agreement of total and regional ASPECTS. METHODS: A comprehensive search was conducted in the Web of Sciences, PubMed, and Scopus databases to identify relevant studies. Inclusion criteria were studies of noncontrast CT performed within 24 hours of ischemic stroke in the middle cerebral artery territory. RESULTS: A total of 20 studies, with 3482 patients, reporting interobserver agreement of total and regional ASPECTS were included in the meta-analysis. The interobserver agreement for total ASPECTS in studies using Kappa coefficient (κ) analysis was substantial (κ = .67, 95% confidence interval [CI]: .57-.78). In studies using intraclass correlation coefficient (ICC) analysis, agreement was excellent (ICC = .84, 95% CI: .77-.90). Interobserver agreement was higher in studies in which the observer was unblinded to clinical scenario in both groups (κ = .74, 95% CI: .59-.89, and ICC = .82, 95% CI: .79-.85). Per-region analysis showed that the caudate nucleus had the highest agreement (κ = .68, 95% CI: .60-.76, and ICC = .84, 95% CI: .74-.93), while M2 and internal capsule in Kappa studies (κ = .45, 95% CI: .34-.55 and κ = .47, 95% CI: .28-.66), and M4 and internal capsule in ICC studies (ICC = .54, 95% CI: .43-.64 and ICC = .55, 95% CI: .18-.91) had the lowest agreement. CONCLUSION: This meta-analysis demonstrates substantial to excellent interobserver agreement for total ASPECTS, which supports using this method for stroke treatment. However, findings emphasize the need to consider interobserver agreement in specific regions of ASPECTS for treatment decisions.

The impact of postoperative aspirin in patients undergoing Woven EndoBridge: a multicenter, institutional, propensity score-matched analysis.

BACKGROUND: The Woven EndoBridge (WEB) device is frequently used for the treatment of intracranial aneurysms. Postoperative management, including the use of aspirin, varies among clinicians and institutions, but its impact on the outcomes of the WEB has not been thoroughly investigated. METHODS: This was a retrospective, multicenter study involving 30 academic institutions in North America, South America, and Europe. Data from 1492 patients treated with the WEB device were included. Patients were categorized into two groups based on their postoperative use of aspirin (aspirin group: n=1124, non-aspirin group: n=368). Data points included patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Propensity score matching (PSM) was applied to balance variables between the two groups. RESULTS: Prior to PSM, the aspirin group exhibited significantly higher rates of modified Rankin scale (mRS) mRS 0-1 and mRS 0-2 (89.8% vs 73.4% and 94.1% vs 79.8%, p<0.001), lower rates of mortality (1.6% vs 8.6%, p<0.001), and higher major compaction rates (13.4% vs 7%, p<0.001). Post-PSM, the aspirin group showed significantly higher rates of retreatment (p=0.026) and major compaction (p=0.037) while maintaining its higher rates of good functional outcomes and lower mortality rates. In the multivariable regression, aspirin was associated with higher rates of mRS 0-1 (OR 2.166; 95% CI 1.16 to 4, p=0.016) and mRS 0-2 (OR 2.817; 95% CI 1.36 to 5.88, p=0.005) and lower rates of mortality (OR 0.228; 95% CI 0.06 to 0.83, p=0.025). However, it was associated with higher rates of retreatment (OR 2.471; 95% CI 1.11 to 5.51, p=0.027). CONCLUSIONS: Aspirin use post-WEB treatment may lead to better functional outcomes and lower mortality but with higher retreatment rates. These insights are crucial for postoperative management after WEB procedures, but further studies are necessary for validation.

The Effect of the COVID-19 Pandemic on Academic Research Gender Disparities in Radiology.

RATIONALE AND OBJECTIVES: Gender disparities have long existed in radiology. The COVID-19 pandemic disrupted research activities worldwide and have impacted gender disparities across medical specialties. This study investigates the effect of the COVID-19 pandemic on gender disparities in radiology academic authorship. MATERIALS AND METHODS: A retrospective observational study was conducted using data from 110 843 global and 23 977 US radiology articles. The gender of authors was determined using an automated gender inference tool. Descriptive statistics were applied to explore authorship changes overall globally, in the US as well as across countries and states. RESULTS: Female first-authorship increased globally from 16.9% to 17.6% (p < 0.001), and in the US, from 19.0% to 19.6% (p = 0.19) in the peri-COVID period. The combined female percentage increased from 19.7% to 20.0% globally (p = 0.021), and from 20.2% to 21.1% in the US (p = 0.006). Country-level analysis revealed significant increases in female authorship in Colombia, Denmark, Egypt, France, India, and Japan, while New Zealand demonstrated a decrease in female authorship. In the US, Florida, Indiana, Louisiana, Massachusetts, and Ohio experienced increases in female authorship, whereas South Carolina demonstrated a decrease in female authorship. CONCLUSION: In contrast with other medical fields, the study demonstrates that radiology experienced a slight increase in female authorship in radiology research globally and in the US during the COVID period. While the pandemic may have influenced these findings, further research is needed to establish regional causal relationships and identify best practices for promoting gender equity in radiology research.

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.

Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

Influential Radiology Figures and Organizations in Social Media.

PURPOSE: With social media becoming a vibrant hub for the radiology community, highlighting expert leaders and trustful conduits of information in the virtual field is proving crucial. The aim of this study was to identify and describe the most prominent and influential figures and organizational accounts to follow in radiology. METHODS: Influence scores for the topic "radiology" on Twitter (now known as X) were computed using the Right Relevance machine learning service. Top influencers were classified according to gender, geography, physician degree, areas of influence, subspecialization, influence score, title, affiliated institution, dual degree, medical school origin, content type, and research activity. Statistical analysis was performed assessing variable correlations. RESULTS: In the top quartile of influential figures, 87% were physicians, 60% men, and 93% located in the United States. Prevalent backgrounds included neuroradiology (21%), abdominal imaging (12%), and artificial intelligence (11%). Of the top 100 figures, 81% were US graduates, 97% held medical degrees, and 28% had dual degrees. Fifty-eight percent provided educational content. A majority held leadership positions (58%) and academic professorship titles (70%). The median h index, publication number, and citation number were 14, 49, and 881, respectively. No significant correlation was noted between influence score and academic rank or research output. CONCLUSIONS: Virtual presence is becoming integral to health care professions and academic spheres, unfolding great potential for enhancing the sense of belonging, advocacy, recruitment, and fostering new relationships. Having a core of influential leaders and organizations to follow can serve as a resource for the community members and aspiring students building a positive connected basis for radiology's thriving future.

Common Data Elements Analysis of Mechanical Thrombectomy Clinical Trials for Acute Ischemic Stroke with Large Core Infarct.

BACKGROUND: Clinical trials addressing large core acute ischemic stroke (AIS) are ongoing across multiple international groups. Future development of clinical guidelines depends on meta-analyses of these trials calling for a degree of homogeneity of elements across the studies. This common data element study aims to provide an overview of key features of pertinent large core infarct trials. METHODS: PubMed and ClinicalTrials.gov databases were screened for published and ongoing clinical trials assessing mechanical thrombectomy in patients with AIS with large core infarct. Nested Knowledge AutoLit living review platform was utilized to categorize primary and secondary outcomes as well as inclusion and exclusion criteria for patient selection in the trials. RESULTS: The most reported data element was ASPECTS score but with varied definitions of what constitutes large core. Non-utility-weighted modified Rankin score (mRS) was reported in 6/7 studies as the primary outcome, while the utility-weighted mRS was the outcome of interest in the TESLA trial, all of them at the 3 months mark, with only LASTE looking for mRS shift at the 6 months mark. Secondary outcomes had more variations. Mortality is reported separately only in 4/7 trials, all at the 3­month mark. Additionally, the TENSION trial reported the frequency of serious adverse events, including mortality, at the 1­week and 12-month mark. DISCUSSION: Overall, in large core trials there is a large degree of heterogeneity in the collected data elements. Differences in definition and timepoints render reaching a unified standard difficult, which hinders high quality meta-analyses and cohesive evidence-driven synthesis.

Long-term outcomes of flow diversion for unruptured intracranial aneurysms: a systematic review and meta-analysis.

BACKGROUND: Flow diverters have been widely used in clinical practice for more than a decade. However, most outcome data are limited to 1 year timepoints. This study aims to offer meta-analysis data on long-term (>1 year) safety and effectiveness results for patients with aneurysms treated with flow diverters. METHODS: PubMed, Web of Science, Embase, and SCOPUS were searched up to February 24, 2022 using the AutoLit platform. We included primary studies assessing the long-term outcomes for flow diverter devices to manage unruptured internal carotid artery aneurysms with a follow-up period of >1 year. The meta-analysis was carried out using Comprehensive Meta-Analysis software (CMA). RESULTS: Eleven studies were included in the meta-analysis. The pooled occlusion rates after flow diversion treatment for unruptured intracranial brain aneurysms were 77%, 87.4%, 84.5%, 89.4%, 96% for 1 year, 1-2 years, 2 years, 3 years, and 5 years follow-up, respectively. The in-stent stenosis rate was 4.8% and the retreatment rate for the long-term follow-up period was 5%. No delayed rupture of the aneurysm was reported, and there was one case of delayed ischemic stroke. The sensitivity analysis of the prospective studies showed a complete occlusion rate of 83.5% and 85.2% for 1 and 3 years of follow-up, respectively. CONCLUSION: Flow diverters are safe and effective in short- and long-term follow-up and rarely cause serious delayed side effects.

Operator assessment versus core laboratory adjudication of recanalization following endovascular treatment of acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Successful recanalization after endovascular thrombectomy serves as the primary endpoint in clinical trials and is a crucial predictor of long-term outcomes. Radiographic outcomes for various interventions have been shown to vary based on the type of interpreter, including the site interventionalist compared with an independent reader. OBJECTIVE: To compare angiographic outcomes in stroke thrombectomy procedures based on the type of reader. METHODS: A systematic literature search was conducted in Medline, EMBASE, Scopus, and Web-of-Science through February 2022. We included primary studies that reported core laboratory-read and operator angiographic outcomes after mechanical thrombectomy for ischemic stroke. Furthermore, study-defined successful recanalization data were collected. RESULTS: Eight studies were included with 4797 patients, 51.2% of whom were male. Four thousand, four hundred and thirty-one patients had core readings, and 4211 had operator readings. Study-defined successful recanalization was significantly higher for operator (84%, 3543/4211) examinations than for core laboratory-read (78.4%, 3476/4431) examinations (p<0.001; OR=1.462, 95% CI 1.175 to 1.819). The modified Thrombolysis in Cerebral Infarction (mTICI) scale score of ≥2 b was higher for operator (85%, 3341/3929) examinations than for core laboratory-read (78.6%, 3107/3952) examinations (p<0.001; OR=1.349, 95% CI 1.071 to 1.701). mTICI 3 was significantly higher for operator (54.6%, 1000/1832) examinations than for core laboratory-read (39.9%, 731/1832) examinations (p<0.001; OR=1.823, 95% CI 1.598 to 2.081). CONCLUSION: Operator angiographic reads are statistically significantly higher than core laboratory-read readings following stroke thrombectomy, especially for complete recanalization. These differences should be considered when interpreting reports of angiographic outcomes after thrombectomy.

Bioactive secondary metabolites from marine Actinomyces sp. AW6 with an evaluation of ADME-related physicochemical properties.

This study was designed to evaluate the antimicrobial, antioxidant, and cytotoxic potentials of the marine actinomycetes spp. isolated from the Red Sea water, Hurghada, Egypt. Out of 80 actinomycetes isolates, one isolate AW6 was selected based on its antioxidant activity (IC50 about 5.24 µg/mL which scavenged 91% of formed DPPH free radicals) and antimicrobial potential against E. coli, S. aureus, B. subtilis, and P. aeruginosa, A. niger, and C. albicans. The strain was identified based on phenotypic and genotypic analysis, and deposited in the GenBank with accession number OK090864.1. Cultivation of the selected strain on rice, chromatographic purification, and structural elucidation led to the isolation of two compounds C1: umbelliferone, and C2: 1-methoxy-3-methyl-8-hydroxy-anthraquinone. The antimicrobial activity of the obtained compounds showed that C1 and C2 have low antibacterial activity toward S. aureus and E. coli with no pronounced activity toward P. aeruginosa, C. albicans, and A. niger. Additionally, the antioxidant activity of C1 and C2 revealed that C2 has a good antioxidant activity, with DPPH scavenging activity reaching (55.25%), followed by C1 (30.20%). Moreover, both compounds displayed anti-Gyr-B enzyme activity with IC50 value of (3.79 ± 0.21 µM) for C1, and (IC50 = 13 ± 0.71 µM) for C2. The ADME-related physicochemical properties of the obtained compound were predicted using SwissADME web tools and the ProToxii webserver was used to estimate in silico toxicity.

Design, synthesis, docking, and anticancer evaluations of phthalazines as VEGFR-2 inhibitors.

Twenty new N-substituted-4-phenylphthalazin-1-amine derivatives were designed, synthesized, and evaluated for their anticancer activities against HepG2, HCT-116, and MCF-7 cells as VEGFR-2 inhibitors. HCT-116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 7f was found to be the most potent derivative among all the tested compounds against the three cancer cell lines, with 50% inhibition concentration, IC50 = 3.97, 4.83, and 4.58 µM, respectively, which is more potent than both sorafenib (IC50 = 9.18, 5.47, and 7.26 µM, respectively) and doxorubicin (IC50 = 7.94, 8.07, and 6.75 µM, respectively). Fifteen of the synthesized derivatives were selected to evaluate their inhibitory activities against VEGFR-2. Compound 7f was found to be the most potent derivative that inhibited VEGFR-2 at an IC50 value of 0.08 µM, which is more potent than sorafenib (IC50 = 0.10 µM). Compound 8c inhibited VEGFR-2 at an IC50 value of 0.10 µM, which is equipotent to sorafenib. Moreover, compound 7a showed very good activity with IC50 values of 0.11 µM, which is nearly equipotent to sorafenib. In addition, compounds 7d, 7c, and 7g possessed very good VEGFR-2-inhibitory activity, with IC50 values of 0.14, 0.17, and 0.23 µM, respectively.

Activity of probiotics from food origin for oxalate degradation.

Kidney stones composed of oxalate are a significant health problem. It has been suggested that modification of the intestinal microbiota to reduce the amount of oxalate in the digestive system could be an effective treatment. There have been several studies into the use of lactic acid bacteria for the degradation of intestinal oxalates. We isolated 88 lactic acid bacteria strains from a range of dairy products, and screened for their ability to degrade oxalate. Using the oxalate-degrading Enzymatic Activity Index and the viable cell counts, five strains of Lactobacillus fermentum and two strains of Lactobacillus gastricus were identified as having strong oxalate degradation abilities, and were further investigated. All seven strains were able to tolerate acid (pH 4 and 3), bile salts (0.3%), phenol (0.3%), and to produce exopolysaccharides. They were resistant to a wide range of antibiotics. Among these strains, Lactobacillus fermentum NRAMJ5 and Lactobacillus gastricus NRAMJ2 were, therefore, good candidates as probiotics for managing hyperoxaluria.

Design and discovery of new antiproliferative 1,2,4-triazin-3(2H)-ones as tubulin polymerization inhibitors targeting colchicine binding site.

Thirty-five new colchicine binding site inhibitors have been designed and synthesized based on the 1,2,4-triazin-3(2H)-one nucleus. Such molecules were synthesized through a cascade reaction between readily accessible α-amino ketones and phenyl carbazate as a masked N-isocyanate precursor. The synthesized derivatives are cisoid restricted combretastatin A4 analogues containing 1,2,4-triazin-3(2H)-one in place of the olefinic bond, and they have the same essential pharmacophoric features of colchicine binding site inhibitors. The synthesized compounds were evaluated in vitro for their antiproliferative activities against a panel of three human cancer cell lines (MCF-7, HepG-2, and HCT-116), using colchicine as a positive control. Among them, two compounds 5i and 6i demonstrated a significant antiproliferative effect against all cell lines with IC50 ranging from 8.2 - 18.2 µM. Further investigation was carried out for the most active cytotoxic agents as tubulin polymerization inhibitors. Compounds 5i and 6i effectively inhibited microtubule assembly with IC50 values ranging from 3.9 to 7.8 µM. Tubulin polymerization assay results were found to be comparable with the cytotoxicity results. The cell cycle analysis revealed significant G2/M cell cycle arrest of the analogue 5i in HepG-2 cells. The most active compounds 4i, 4j, 5 g, 5i and 6i did not induce significant cell death in normal human lung cells Wl-38, suggesting their selectivity against cancer cells. Also, These compounds upregulated the level of active caspase-3 and boosted the levels of the pro-apoptotic protein Bax by five to seven folds in comparison to the control. Moreover, apoptosis analyses were conducted for compound 5i to evaluate its apoptotic potential. Finally, in silico studies were conducted to reveal the probable interaction with the colchicine binding site. ADME prediction study of the designed compounds showed that they are not only with promising tubulin polymerization inhibitory activity but also with favorable pharmacokinetic and drug-likeness properties.

Formation of electroactive biofilms derived by nanostructured anodes surfaces.

Microbial fuel cells (MFCs) have significant interest in the research community due to their ability to generate electricity from biodegradable organic matters. Anode materials and their morphological structures play a crucial role in the formation of electroactive biofilms that enable the direct electron transfer. In this work, modified electrodes with nanomaterials, such as multiwalled carbon nanotubes (MWCNTs), reduced graphene oxide (rGO), Al2O3/rGO or MnO2/MWCNTs nanocomposites were synthesized, characterized and utilized to support the growth of electrochemically active biofilms. The MFC's performance is optimized using anode-respiring strains isolated from biofilm-anode surface, while the adjusted operation is conducted with the consortium of (Enterobacter sp.). Besides the formation of matured biofilm on its surface, MnO2/MWCNTs nanocomposite produced the highest electrical potential outputs (710 mV) combined with the highest power density (372 mW/m2). Thus, a correlation between the anode nanostructured materials and the progression of the electrochemically active biofilms formation is presented, allowing new thoughts for enhancing the MFC's performance for potential applications ranging from wastewater treatment to power sources.

Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of quinazolin-4(3H)-one derivatives as potential PPARγ and SUR agonists.

Peroxisome proliferator-activated receptor gamma (PPARγ) and sulfonylurea receptor (SUR) play crucial roles in management of type-2 diabetes mellitus. In this study, a series of novel quinazoline-4(3H)-one-sulfonylurea hybrids were designed and synthesized as dual PPARγ and SUR agonists. The synthesized compounds were evaluated for their in vivo anti-hyperglycemic activities against STZ-induced hyperglycemic rats. Four compounds (19a, 19d, 19f and 25g) demonstrated potent activities with reduction in blood glucose levels of 40.43, 46.42, 41.23 and 42.50 %, respectively. The most active ten compounds were further evaluated in vitro for their PPARγ binding affinities and insulin-secreting abilities. Compounds 19b, 19d, 19f, 25f and 25g exhibited the highest affinities against PPARγ with IC50 values of 0.371, 0.350, 0.369, 0.408 and 0.353µM, respectively. In addition, compounds 19d, 19f, and 25d showed the highest insulin-secreting activities with EC50 values of 0.97, 1.01 and 1.15µM, respectively. Furthermore, molecular docking and pharmacophore generation techniques were carried out to investigate binding patterns and fit values of the designed compounds with PPARγ and SUR, respectively. Also, two QSAR models were generated to explore the structural requirements controlling the different biological activities of the synthesized compounds against PPARγ and SUR.