Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins-VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID-25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.

Total pancreatectomy, splenectomy and remnant gastrectomy for invasive intraductal papillary mucinous neoplasm (IPMN) after prior Roux-en-Y gastric bypass.

A female patient in her 50s presented with abdominal pain, nausea and jaundice. She had a history of prior Roux-en-Y gastric bypass and her body mass index was 52.5 kg/m2 Biochemical testing revealed a total bilirubin level of 14.3 mg/dL (normal<1.2 mg/dL) and carbohydrate antigen 19-9 of 38.3 units/mL (normal<36.0 units/mL). CT demonstrated a 3.2 cm pancreatic head mass, biliary and pancreatic duct dilation and cystic replacement of the pancreas. The findings were consistent with a diagnosis of mixed-type intraductal papillary mucinous neoplasm (IPMN) with invasive malignancy. The patient's Roux-en-Y anatomy precluded endoscopic biopsy, and she underwent upfront resection with diagnostic laparoscopy, open total pancreatectomy, splenectomy and remnant gastrectomy with reconstruction. Pathology confirmed T2N1 pancreatic adenocarcinoma, 1/29 lymph nodes positive and diffuse IPMN. She completed adjuvant chemotherapy. IPMNs have malignant potential and upfront surgical resection should be considered without biopsy in the appropriate clinical setting.

Unveiling the ESR1 Conformational Stability and Screening Potent Inhibitors for Breast Cancer Treatment

BACKGROUND: The current study recognizes the significance of estrogen receptor alpha (ERα) as a member of the nuclear receptor protein family, which holds a central role in the pathophysiology of breast cancer. ERα serves as a valuable prognostic marker, with its established relevance in predicting disease outcomes and treatment responses. METHOD: In this study, computational methods are utilized to search for suitable drug-like compounds that demonstrate analogous ligand binding kinetics to ERα. RESULTS: Docking-based simulation screened out the top 5 compounds - ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569 against the targeted protein. Further, their dynamics studies reveal that the compounds ZINC13377936 and NCI35753 exhibit the highest binding stability and affinity. CONCLUSION: Anticipating the competitive inhibition of ERα protein expression in breast cancer, we envision that both ZINC13377936 and NCI35753 compounds hold substantial promise as potential therapeutic agents. These candidates warrant thorough consideration for rigorous In vitro and In vivo evaluations within the context of clinical trials. The findings from this current investigation carry significant implications for the advancement of future diagnostic and therapeutic approaches for breast cancer.

Determinants of initiation, continuation and cessation of smokeless tobacco use among pregnant and lactating women: a qualitative study from low-income communities in urban India.

Smokeless tobacco (SLT) consumption increases the risk of cardiovascular diseases and cancer and leads to adverse reproductive health outcomes among women and newborns. This study examines the factors associated with initiation, continuation and cessation of SLT use among women in the reproductive age so as to formulate and include prevention and cessation interventions from its inception. The study was conducted in urban low-income communities in India. Using snowball and purposive sampling techniques, in-depth interviews were conducted with 20 pregnant and 22 lactating women who currently used SLT products. Data were analysed using thematic analysis with the help of QSR NVivo software. Findings revealed that factors such as people influencing usage change with different life stages including pre-marital and post-marital periods. Perceived health benefits, altered taste preferences during pregnancy and social influences were also studied. Women were found to be more aware of the harmful effects of tobacco during pregnancy than during breastfeeding. Social stigma around women consuming tobacco acted as a major driving factor for cessation. Most of the participants were willing to quit but were not aware of any technique or programme for cessation. The findings of the study highlight the need to develop behavioural change intervention tools, which are culturally and locally appropriate and have a gender-sensitive approach. Different socio-cultural factors associated with initiation/cessation at different life stages should also be taken into consideration while developing these tools.

Timing is everything: outcomes of 30,259 delayed cholecystectomies in New York State.

BACKGROUND: The timing of cholecystectomy in relation to outcomes has been debated. To our knowledge, there are no large population-based studies looking at outcomes and complications of delayed cholecystectomy [DC] (> 72 h after presentation). This study utilizes a statewide database to determine whether there are differences in patient outcomes for DC performed at 3-4 days, 5-6 days, and ≥ 7 days after presentation. METHODS: The New York SPARCS database was used to identify adult patients presenting with a diagnosis of acute cholecystitis from 2005 to 2017. Patients aged < 18, those with missing identifier or procedure-date information, those who underwent early cholecystectomy < 72 h or upon readmission, were excluded. Patients undergoing DC at 3-4 days, 5-6 days, and ≥ 7 days were compared in terms of overall complications, hospital length of stay (LOS), 30-day readmissions/emergency department (ED) visits, and 30-day mortality. RESULTS: 30,259 patients were identified. DCs were performed within 3-4 days (n = 19,845, 65.6%), 5-6 days (n = 6432, 21.3%), and ≥ 7 days (n = 3982, 13.2%). There was a stepwise deterioration in outcomes with increased delay to surgery (Fig. 1). When comparing 3-4 and ≥ 7 days, overall complications (OR = 0.418, 95% CI: 0.387-0.452), 30-day readmissions (OR = 0.609, 95% CI: 0.549-0.674), 30-day ED visits (OR = 0.697, 95% CI: 0.637-0.763), 30-day mortality (OR = 0.601, 95% CI: 0.400-0.904), and LOS (OR = 0.729, 95% CI: 0.710-0.748) were lower in the 3-4 day cohort. CONCLUSIONS: DC within 3-4 days is associated with fewer complications, readmissions and ED visits, and reduced LOS compared to DC at 5-6 or ≥ 7 days after presentation. In addition, 30-day mortality was also significantly different comparing 3-4 with ≥ 7-day cohorts. These data are important for guiding patients in the consent process and may point to choosing an earlier interval cholecystectomy for high-risk patients.