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The development and application of evolutionary algorithms (EAs) and other metaheuristics for the optimisation of water resources systems has been an active research field for over two decades. Research to date has emphasized algorithmic improvements and individual applications in specific areas (e.g. model calibration, water distribution systems, groundwater management, river-basin planning and management, etc.). However, there has been limited synthesis between shared problem traits, common EA challenges, and needed advances across major applications. This paper clarifies the current status and future research directions for better solving key water resources problems using EAs. Advances in understanding fitness landscape properties and their effects on algorithm performance are critical. Future EA-based applications to real-world problems require a fundamental shift of focus towards improving problem formulations, understanding general theoretic frameworks for problem decompositions, major advances in EA computational efficiency, and most importantly aiding real decision-making in complex, uncertain application contexts.

AbstractAim:To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity.Methods:Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2.Results:The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity.Conclusion:This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity. [ABSTRACT FROM AUTHOR]

QSAR study of derivatives of testosterone has been made with the help of quantum mechanical parameters such as Absolute Hardness (η) and Electronegativity (χ). These two parameters have been derived with the help of density functional theory. The 3-D modeling and geometry optimization of all the compounds have been done with the help of PCMODEL software and semiempirical PM3 calculations performed with the help of WinMOPAC-7.21 software. The absolute hardness provides valuable information due to maximum hardness principle and used in development of QSAR. The information provided by electronegativity is not as clear as in case of absolute hardness. [Copyright &y& Elsevier]

Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 ( NUDT15 ) and thiopurine S -methyltransferase ( TPMT ) genotype, along side thiopurine S -methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted., (© 2024 Dunja Urbančič et al., published by Sciendo.)

Advances in research, including novel biomarker identification and patient stratification, have significantly improved the therapy for childhood acute lymphoblastic leukemia (ALL), though access to improved healthcare services varies across geographical regions. In an effort to evaluate the advances in therapeutic approaches, we performed a retrospective analysis of childhood ALL in Kosovo. Our retrospective analysis included 225 cases diagnosed between 2008 and 2023, representing 52% of 429 diagnosed childhood cancers. The average annual incidence was 14, with a median age diagnosis of seven years, and a male predominance (59.54%). Patients were categorized into risk groups, with the majority (43%) in the standard-risk category. We identified five different treatment protocols for this study period. Over 61% of patients achieved remission after the first chemotherapy cycle and we observed a 20% mortality rate. Survival analysis showed that 55% and 40% of patients achieved 2-year and 5-year event-free survival (EFS), respectively, with significant differences across risk groups. Treatment advancements significantly correlated with improved survival rates, achieving a 5-year overall survival (OS) of 88% in the currently used standardized AIEOP-BFM-2009 protocol. Our study emphasizes the need for continued research and customized care strategies to enhance clinical outcomes.

Competing Interests: The authors declare no competing interests.

Introduction and objectives Liver transplantation and its indications represent an increased burden on patients' health. This can be represented in a variety of ways, such as in emergency visits, unscheduled clinic visits, and unanticipated admissions. This study aims to analyze emergency department (ED) visits, the most common presenting complaints, and the outcomes of those visits. Methods A retrospective observational study was performed in which electronic medical records were reviewed for all patients who underwent liver transplantation and presented to the emergency department between October 2011 and October 2021. The following data were collected: demographics, comorbidities, liver transplant features, and emergency department visit data and outcomes. Recurrent visits were assessed and labeled as first, second, third, fourth, and fifth or more. Results A total of 699 patients and 5,225 visits were included in the analysis. Living donors accounted for 80% of all transplants. The mean post-operative length of stay was 22.6 ± 17.8. The majority of patients (74%) had at least one comorbidity, with diabetes (47%), hypertension (31%), and chronic kidney disease (CKD) (16%) being the commonest comorbidities; however, comorbidities were not associated with an increased risk of emergency department visits. Out of the 5,225 visits to the emergency department, 2,265 (41%) were within the first year. Emergency department visits in the first seven days after discharge amounted to 22% of total first visits. By 30 days, six months, and one year, they increased to 46%, 83%, and 91%, respectively. Living donor recipients had an average of 7.3 ED visits as compared to deceased donor recipients, who had an average of 8.4 ED visits. The most common presenting complaints were gastrointestinal (GI) symptoms (18%), infectious disease symptoms (9%), and respiratory symptoms (8%). There were a total of 296 patients who were readmitted at least once since discharge after liver transplantation. Conclusion The majority of first-time presentations to ED occurred in the first year post-transplant, marking this time period as critical for liver transplant patients. Our study also highlighted the continual presentations of liver transplant patients to the ED a few years post-transplant. This requires close scrutiny of the main causes of such presentations as well as comparison with other transplant cases to identify whether they are specific to liver transplants or not., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Aljumaa et al.)

Introduction: An increasing number of pediatric patients with inherited metabolic disorders are reaching adulthood. In addition, many patients are diagnosed for the first time in adult life due to improved awareness of these disorders and the availability of advanced diagnostic technology. Knowledge of these inherited metabolic disorders in adults is crucial for the emergency physician to promptly recognize their acute illness and appropriately manage them in the emergency department., Objective: This review provides an overview of various inherited metabolic disorders which present to the emergency department with acute metabolic decompensation., Evaluation and Management: Acute illness in these patients is often triggered by a catabolic event such as intercurrent illness, fasting, postpartum, or use of certain medication. It may present in a variety of ways related to severe hyperammonemia, metabolic acidosis, leucine encephalopathy or hypoglycemia. In this review, we describe the clinical presentation, evaluation and immediate management of their critical illness in the emergency department., Conclusion: Acute metabolic decompensation is a life-threatening condition. The emergency physician is usually the first provider to evaluate these patients when they present to the emergency department. Early recognition of their illness and prompt management of these cases improve patient outcomes., Competing Interests: Declaration of Competing Interest All authors declare no competing interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objective: The epidemiology of Nipah virus (NiV) was shortly seen in many Asian countries like Malaysia, Bangladesh and India most recently. Nipah virus also synonym as bat born virus is transmitted primarily by fruit bats. The 2 different strains transmitted are Hendra (highly pathogenic) and Cedar (non-pathogenic). The present study was attempt to develop recombinant protein based reagents for molecular diagnosis of Nipah., Materials and Methods: The different primer sets were developed using bioinformatics software DNASTAR. The E. coli cells were used for recombinant protein expression., Results: The NiV 'G' region primers were designed and amplified for 1 kb fragment and cloned. The NiV 'G' fragments were sub-cloned in pET-28(+) B and pGEX-5x-1. Recombinant protein thus obtained in soluble form in both the cases was essayed using western blot. The result showed the protein expression yield was more in pET-28(+) B with low stability and vice versa for pGEX-5x-1., Conclusion: The antibodies raised from the protein can be used as diagnostic reagent for detection of NiV. Thus, a new diagnostic technique can be industrialized.

Known as systemic sclerosis (SSc), this autoimmune rheumatic disease has vast pathogenesis on many organs, including kidneys. It can lead to the point where the patient's survival relies entirely on dialysis. This report has basically focused on scleroderma renal crisis (SRC), which is the most serious renal manifestation of SSc, characterized by renal failure and sudden onset of hypertension. A 44-year-old man was hospitalized with hypertension, headache, vertigo, nausea, rhinorrhea, reflux, dysphagia, dyspnea (Fc II), visual impairment, mechanical arthralgia, and edema (+3) accompanied by a rare skin lesion. Raynaud's phenomenon was also remarkable in fingers and toes. According to signs and symptoms, SSc diagnosed and the proper treatment was applied. It is of great importance that in the case of malignant hypertension in patients with scleroderma, renal crisis always be kept in mind.

The dorsal raphe nucleus (DRN) is a major serotonin (5-hydroxytryptamine, 5-HT)-producing region in the central nervous system. It receives glutamatergic inputs from several brain regions, which are reciprocally modulated by serotonergic signals. We investigated whether serotonin 5-HT 4 receptors (5-HT 4 Rs) play a role in the development of glutamatergic control of the DRN, with an emphasis on cortical inputs. Double-label immunohistochemistry and confocal microscopy were used to quantify vesicular glutamate transporter 1 (vGluT1)-immunoreactive terminals in the DRN of mice with a null-mutation in the 5-HT 4 R gene. We found no significant change in the overall density of vGluT1-positive terminals in homozygous and heterozygous mice, but heterozygous mice had a significantly higher density of vGluT1-positive terminals contacting serotonergic neurons. These results suggest that altered 5-HT 4 R expression may affect the development of cortical glutamatergic control of the DRN., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Emergency color codes were developed to alert healthcare personnel in a hospital to critical situations. They are often developed independently by each hospital, leading to variability. This could be a source of confusion to healthcare personnel, who move frequently between hospitals and may work at multiple hospitals. This study evaluated the variability of emergency codes for different critical events in hospitals in Riyadh., Methods: A prospective, cross-sectional survey was carried out on a representative sample of hospitals. Twenty-four of 28 hospitals took part in the study. Semi-structured questionnaires were completed by the Quality/Safety Department of each hospital, on general hospital characteristics, emergency department characteristics, code-response mock-up, code determination, emergency codes used and code meanings., Results: Thirty-four different codes were used across hospitals. The codes used most variably were yellow (10 meanings), orange, black, green (7 meanings each), and gray (5 meanings), while the most consistently used code was 'Code Red' for 'Fire' in 75% of hospitals. Another source of variability was the use of non-color codes, representing 7.7% of total codes., Conclusions: There is large variability in the type and meaning of emergency codes between hospitals in Riyadh City, reflecting a lack of standardization. Hospitals use color and non-color emergency codes, which could cause confusion to responders and mitigate the effectiveness and speed of response in critical events.