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BioMedicine 2024Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and...
BACKGROUND
Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.
METHODS
Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline.
RESULTS
Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from justified the Lipinski's Rule of 5.
CONCLUSION
Viscosalactone obtained from may act as promising drug candidate to fight against metastatic breast cancer.
PubMed: 38939099
DOI: 10.37796/2211-8039.1448 -
BioImpacts : BI 2024Neuroglioma, a classification encompassing tumors arising from glial cells, exhibits variable aggressiveness and depends on tumor grade and stage. Unraveling the EGFR...
INTRODUCTION
Neuroglioma, a classification encompassing tumors arising from glial cells, exhibits variable aggressiveness and depends on tumor grade and stage. Unraveling the EGFR gene alterations, including amplifications (unaltered), deletions, and missense mutations (altered), is emerging in glioma. However, the precise understanding of emerging EGFR mutations and their role in neuroglioma remains limited. This study aims to identify specific EGFR mutations prevalent in neuroglioma patients and investigate their potential as therapeutic targets using FDA-approved drugs for repurposing approach.
METHODS
Neuroglioma patient's data were analyzed to identify the various mutations and survival rates. High throughput virtual screening (HTVS) of FDA-approved (1615) drugs using molecular docking and simulation was executed to determine the potential hits.
RESULTS
Neuroglioma patient samples (n=4251) analysis reveals 19% EGFR alterations with most missense mutations at V774M in exon 19. The Kaplan-Meier plots show that the overall survival rate was higher in the unaltered group than in the altered group. Docking studies resulted the best hits based on each target's higher docking score, minimum free energy (MMGBSA), minimum kd, ki, and IC50 values. MD simulations and their trajectories show that compounds ZINC000011679756 target unaltered EGFR and ZINC000003978005 targets altered EGFR, whereas ZINC000012503187 (Conivaptan, Benzazepine) and ZINC000068153186 (Dabrafenib, aminopyrimidine) target both the EGFRs. The shortlisted compounds demonstrate favorable residual interactions with their respective targets, forming highly stable complexes. Moreover, these shortlisted compounds have drug- like properties as assessed by ADMET profiling.
CONCLUSION
Therefore, compounds (ZINC000012503187 and ZINC000068153186) can effectively target both the unaltered/altered EGFRs as multi-target therapeutic repurposing drugs towards neuroglioma.
PubMed: 38938756
DOI: 10.34172/bi.2023.28876 -
Frontiers in Physiology 2024Monopterus albus is one of China's renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in aquaculture...
Monopterus albus is one of China's renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%-85.33%, which was significantly higher than that of the other three bait groups ( < 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) ( > 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups ( < 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO -N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups ( < 0.05), there was no significant difference in TAN content among the treatment groups ( > 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups ( < 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups ( > 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, could potentially serve as one of the alternative feeds during the initial stages of juveniles stocking.
PubMed: 38938746
DOI: 10.3389/fphys.2024.1403391 -
Frontiers in Cardiovascular Medicine 2024The relationship between the blood urea nitrogen to creatinine ratio (BCR) and the risk of in-hospital mortality among intensive care unit (ICU) patients diagnosed with...
BACKGROUND
The relationship between the blood urea nitrogen to creatinine ratio (BCR) and the risk of in-hospital mortality among intensive care unit (ICU) patients diagnosed with venous thromboembolism (VTE) remains unclear. This study aimed to assess the relationship between BCR upon admission to the ICU and in-hospital mortality in critically ill patients with VTE.
METHODS
This retrospective cohort study included patients diagnosed with VTE from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was in-hospital mortality. Univariate and multivariate logistic regression analyses were conducted to evaluate the prognostic significance of the BCR. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cut-off value of BCR. Additionally, survival analysis using a Kaplan-Meier curve was performed.
RESULTS
A total of 2,560 patients were included, with a median age of 64.5 years, and 55.5% were male. Overall, the in-hospital mortality rate was 14.6%. The optimal cut-off value of the BCR for predicting in-hospital mortality in critically ill VTE patients was 26.84. The rate of in-hospital mortality among patients categorized in the high BCR group was significantly higher compared to those in the low BCR group (22.6% vs. 12.2%, < 0.001). The multivariable logistic regression analysis results indicated that, even after accounting for potential confounding factors, patients with elevated BCR demonstrated a notably increased in-hospital mortality rate compared to those with lower BCR levels (all < 0.05), regardless of the model used. Patients in the high BCR group exhibited a 77.77% higher risk of in-hospital mortality than those in the low BCR group [hazard ratio (HR): 1.7777; 95% CI: 1.4016-2.2547].
CONCLUSION
An elevated BCR level was independently linked with an increased risk of in-hospital mortality among critically ill patients diagnosed with VTE. Given its widespread availability and ease of measurement, BCR could be a valuable tool for risk stratification and prognostic prediction in VTE patients.
PubMed: 38938654
DOI: 10.3389/fcvm.2024.1400915 -
The Journal of Poultry Science 2024This study evaluated the effects of whole flaxseed (WFS), fish oil (FO), and different sources of Se, Zn, and Fe (inorganic, organic, and nano-source) on egg production,...
This study evaluated the effects of whole flaxseed (WFS), fish oil (FO), and different sources of Se, Zn, and Fe (inorganic, organic, and nano-source) on egg production, quality, sensory attributes, and serum protein metabolites in laying hens. A total of 144 hens were divided into six groups with six replicates of four hens each. Hens were fed six diets as follows: 1) control diet; 2) 7.5%WFS+1.5%FO; 3) 7.5%WFS+1.5%FO+175 mg/kg vitamin E (VE); 4) 7.5%WFS+1.5%FO+175 mg/kg VE + inorganic sources of Se, Zn, and Fe (ISeZnFe); 5) 7.5%WFS+1.5%FO+175 mg/kg VE + organic sources of Se, Zn, and Fe (OSeZnFe); 6) 7.5%WFS+1.5%FO+175 mg/kg VE + nano-source of Se, Zn, and Fe (NSeZnFe) from 40-50 weeks of age. Laying hens fed 7.5% WFS, 1.5% FO, and different sources of trace elements in their diets had no negative effects on laying rate, egg weight, egg mass, feed intake, feed conversion ratio, body weight change, or survival rate compared to that of hens fed the control diet. Dietary treatments did not negatively affect the external and internal egg characteristics or egg sensory attributes. Feeding 7.5%WFS+1.5%FO+VE+ISeZnFe positively influenced yolk color in fresh eggs. Dietary treatments had a significant impact on egg nutritional composition, with the highest levels of macronutrients found in eggs from hens fed the 7.5%WFS+1.5%FO+VE+NSeZnFe treatment. The highest plasma globulin concentrations were observed in hens fed organic and nano-source trace elements. The same diets reduced plasma uric acid levels. Based on these findings, the inclusion of organic or nano-source trace minerals in diets containing WFS and FO positively affected egg quality and hen protein metabolites.
PubMed: 38938590
DOI: 10.2141/jpsa.2024021 -
Frontiers in Pediatrics 2024Congenital Heart Disease (CHD) is the most common congenital disorder and a leading cause of infant mortality. Despite improved survival rates, patients with CHD often...
INTRODUCTION
Congenital Heart Disease (CHD) is the most common congenital disorder and a leading cause of infant mortality. Despite improved survival rates, patients with CHD often face malnutrition due to increased metabolic demands, feeding difficulties, and gastrointestinal dysfunction. Malnutrition in CHD is linked to poor short and long-term clinical outcomes. Gastrostomy (GT) is frequently used for long-term enteral support, and laparoscopic GT (LGT) has demonstrated advantages in children without CHD. This study evaluated a modified Georgeson's percutaneous LGT technique and its perioperative complications in children with CHD.
METHODS
We performed an analytical retrospective cohort study from 2018 to 2022, including patients younger than 24 months with a diagnosis of CHD who underwent LGT. The primary outcome evaluated was the presence of complications during surgery and the first thirty postoperative days. Complications were graded using Clavien-Dindo's (CD) classification. Sociodemographic, clinical, and procedure-related variables were collected. A bivariate analysis was performed using STATA 15, and a < 0.05 was considered statistically significant.
RESULTS
Seventy-eight patients were eligible (male 56.41%, Median age 129.5 days, weight: 4.83 kg). The median surgery time was 35 min. The complication rate was 24.36%. The most frequent complications were GT site infection (10.26%), followed by leakage (8.97%) and granuloma formation (6.41%). Conversion to open surgery was significantly associated with postoperative complications ( = 0.002).
CONCLUSION
This modified technique is well-tolerated in children with CHD, demonstrating a low rate of CD grade 3A/3B complications and no grade 4 or 5 complications.
PubMed: 38938503
DOI: 10.3389/fped.2024.1405793 -
British Journal of Haematology Jun 2024Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase...
Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a survival expectation of a few months. In this phase II trial, we assessed the efficacy and safety of the carfilzomib-lenalidomide-dexamethasone (KRD) combination in MCL patients who were relapsed/refractory (R/R) or intolerant to BTKi and in need of treatment. The primary objective of the study was to evaluate the antitumor efficacy of the KRD combination in terms of 12-month overall survival (12-month OS). From September 2019 to December 2020, 16 patients were enrolled from 11 Italian centers. After a median follow-up of 2.37 months (95% CI 0.92-6.47), the 12-month OS was 13%. The rate of grade 3-4 adverse events (AEs) was 35%, and the overall response rate (ORR) was 19%. These results led to the premature termination of enrollment, as defined in the protocol stopping rules. The efficacy of the KRD combination in advanced-stage MCL patients who are R/R to BTKi is unsatisfactory and too toxic.
PubMed: 38938122
DOI: 10.1111/bjh.19617 -
Journal of Cardiothoracic Surgery Jun 2024Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is...
BACKGROUND
Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.
METHODS
This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.
RESULTS
During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07-4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24-12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12-0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13-0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).
CONCLUSIONS
In type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.
Topics: Humans; Male; Female; Retrospective Studies; Platelet Aggregation Inhibitors; Subclavian Artery; Middle Aged; Aortic Dissection; Endovascular Procedures; Aortic Aneurysm, Thoracic; Aged; Clopidogrel; Aspirin; Aorta, Thoracic; Treatment Outcome; Blood Vessel Prosthesis Implantation; Postoperative Complications; Endovascular Aneurysm Repair
PubMed: 38937841
DOI: 10.1186/s13019-024-02932-3 -
BMC Medical Informatics and Decision... Jun 2024Pancreatic cancer possesses a high prevalence and mortality rate among other cancers. Despite the low survival rate of this cancer type, the early prediction of this...
BACKGROUND AND AIM
Pancreatic cancer possesses a high prevalence and mortality rate among other cancers. Despite the low survival rate of this cancer type, the early prediction of this disease has a crucial role in decreasing the mortality rate and improving the prognosis. So, this study.
MATERIALS AND METHODS
In this retrospective study, we used 654 alive and dead PC cases to establish the prediction model for PC. The six chosen machine learning algorithms and prognostic factors were utilized to build the prediction models. The importance of the predictive factors was assessed using the relative importance of a high-performing algorithm.
RESULTS
The XG-Boost with AU-ROC of 0.933 (95% CI= [0.906-0.958]) and AU-ROC of 0.836 (95% CI= [0.789-0.865] in internal and external validation modes were considered as the best-performing model for predicting the mortality risk of PC. The factors, including tumor size, smoking, and chemotherapy, were considered the most influential for prediction.
CONCLUSION
The XG-Boost gained more performance efficiency in predicting the mortality risk of PC patients, so this model can promote the clinical solutions that doctors can achieve in healthcare environments to decrease the mortality risk of these patients.
Topics: Humans; Pancreatic Neoplasms; Retrospective Studies; Male; Female; Middle Aged; Aged; Machine Learning; Risk Assessment; Prognosis; Models, Statistical; Adult; Algorithms
PubMed: 38937795
DOI: 10.1186/s12911-024-02590-4 -
BMC Health Services Research Jun 2024This study investigates the incidence of violence escalation among psychiatric emergency patients admitted to general emergency departments in hospitals in central... (Observational Study)
Observational Study
Incident of violence escalation of patients with psychiatric emergencies boarding in the emergency department in the central region of Thailand and its association: a prospective observational study.
BACKGROUND
This study investigates the incidence of violence escalation among psychiatric emergency patients admitted to general emergency departments in hospitals in central Thailand. In addition, patient and service delivery system factors associated with the survival time of violence escalation in 16 emergency departments in the central region of Thailand are determined. This is a prospective observational study, and the study sample includes 507 psychiatric emergency patients who are ≥ 18 years old. The patients are selected through stratified random and purposive sampling.
METHODS
Patient data-including demographic data, emergency services used, and clinical characteristics-are analyzed using descriptive statistics. The Kaplan-Meier method estimates the violence escalation curve, and the log-rank test compares the violence escalation-free time between the levels of the violent behavior group. In addition, univariable and multivariable Cox proportional hazard analyses are performed to investigate the factors affecting violence escalation.
RESULTS
The incidence of violence escalation in psychiatric emergency patients in the emergency department is 7.3%, whereas the incidence rate of violence escalation is 3 per 100 psychiatric emergency patient visit hours. Factors affecting violence escalation include the violent behavior score at triage (aHR = 2.004; 95% CI: 1.051-3.823) and the nurse competency score (aHR = 0.147; 95% CI: 0.032-0.680).
CONCLUSIONS
Assessing the violent behavior of psychiatric emergency patients at triage may assist emergency providers in monitoring patient behavior and providing early intervention to prevent the escalation of violent behavior. Furthermore, training emergency nurses in psychiatric emergency care is necessary.
Topics: Humans; Thailand; Prospective Studies; Male; Female; Emergency Service, Hospital; Adult; Violence; Incidence; Middle Aged; Mental Disorders
PubMed: 38937780
DOI: 10.1186/s12913-024-11228-0