Real world use of tirzepatide in the treatment of type 2 diabetes in an Arab population.

AIM: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) dual receptor agonist (RA) that reduces glycated haemoglobin (HbA1c) and weight in patients with type 2 diabetes. We assessed the effectiveness of tirzepatide in real-world use in an Arab population. METHODS: Review of clinical data from a specialist outpatient diabetes centre; study time points and outcome measures were pre-specified. RESULTS: Tirzepatide was initiated in 8945 patients between 24 October 2022 and 31 December 2023. Of these, 3686 individuals reached 40 weeks of follow-up. At initiation, the mean ± SD age was 54.1 ± 11.5 years, body mass index 34.6 ± 6.0 kg/m2 and HbA1c 7.3 ± 1.5% (56 ± 17 mmol/mol); 2296 (62%) were switched to tirzepatide from another GLP-RA and 317 (8.6%) reported previous bariatric surgery. The maximum dose dispensed was ≥12.5 mg/week in 1087, 7.5-10.0 mg/week in 1688 and 2.5-5.0 mg/week in 911. The mean 40-week reduction in HbA1c was 0.6 ± 1.2% (8 ± 13 mmol/mol) and the reduction in weight was 4.5 ± 6.9 kg (4.8 ± 7.3%). GLP-RA-naïve patients experienced a significantly greater reduction in HbA1c [1.0 ± 1.3% (11 ± 14 mmol/mol) versus 0.5 ± 1.2% (6 ± 13 mmol/mol), p < .0001] and weight (7.2 ± 8.6 vs. 4.2 ± 6.6 kg, p < .0001) compared with previously exposed individuals. Post-metabolic bariatric surgery patients lost significantly more weight (7.8 ± 9.4 vs. 4.5 ± 7.0 kg, p < .0001). Improvements in blood pressure, lipid profile, and liver transaminases were noted at 40 weeks. Tirzepatide was well tolerated, with 288 (7.8%) of patients discontinuing treatment because of adverse effects, predominantly gastrointestinal. CONCLUSION: In real-world use, tirzepatide significantly reduced HbA1c levels and weight and was well tolerated. Previous GLP-RA use was associated with significantly lesser HbA1c and weight reduction, and previous metabolic bariatric surgery was associated with greater weight loss.

Interleukin-6-to-Albumin Ratio as a Superior Predictor of Mortality in End-Stage Kidney Disease Patients.

INTRODUCTION: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients. METHODS: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time. RESULTS: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality. CONCLUSIONS: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD.

Telomere length and telomere repeat-binding protein in children with sickle cell disease.

BACKGROUND: This study aimed to assess the telomere length and plasma telomere repeat-binding factor 2 (TRF2) levels in addition to other inflammatory markers in children with sickle cell disease (SCD). METHODS: We enrolled 106 children (90 SCD and 26 controls) aged 1-15 years from the Hematology unit of King Fahad Medical City (KFMC), Saudi Arabia. Genomic DNA extracted from blood and leukocyte TL was determined using quantitative reverse transcription PCR, whereas TRF2, C-reactive protein, interleukin-6, and DNA oxidative damage were determined by using respective commercially available assays. RESULTS: Leukocyte TL was inversely correlated with age in the SCD patients (r = -0.24, P = 0.02) and the controls (r = -0.68, P < 0.0001). In addition, SCD patients had significantly shorter TL (7.74 ± 0.81 kb) (P = 0.003) than controls (8.28 ± 0.73 kb). In contrast, no significant difference in TL among the SCD genotypes (HbSS and HbSß0) has been observed. A modest, positive correlation was seen between TL and reticulocyte % (r = 0.21; P = 0.06). There were no significant differences in the TL and TRF2 concentrations between subjects with HbSS and HbSß0 genotypes. CONCLUSIONS: Short leukocyte TL was significantly associated with SCD. An inverse association was observed between TL and hemoglobin. Hydroxyurea treatment revealed no impact on TL. IMPACT: This study explored the TL and plasma TRF2 in Saudi children with SCD. This is the first documentation that SCD children have shorter TL than their healthy counterparts, and no association between TL and TRF2 has been observed. Hydroxyurea treatment showed no impact on TL in children with SCD. This study is the first of its kind in children with SCD. It will pave the way for another study with a larger sample size in a diverse population to scrutinize these findings better.

Hybrid and Deep Learning Approach for Early Diagnosis of Lower Gastrointestinal Diseases.

Every year, nearly two million people die as a result of gastrointestinal (GI) disorders. Lower gastrointestinal tract tumors are one of the leading causes of death worldwide. Thus, early detection of the type of tumor is of great importance in the survival of patients. Additionally, removing benign tumors in their early stages has more risks than benefits. Video endoscopy technology is essential for imaging the GI tract and identifying disorders such as bleeding, ulcers, polyps, and malignant tumors. Videography generates 5000 frames, which require extensive analysis and take a long time to follow all frames. Thus, artificial intelligence techniques, which have a higher ability to diagnose and assist physicians in making accurate diagnostic decisions, solve these challenges. In this study, many multi-methodologies were developed, where the work was divided into four proposed systems; each system has more than one diagnostic method. The first proposed system utilizes artificial neural networks (ANN) and feed-forward neural networks (FFNN) algorithms based on extracting hybrid features by three algorithms: local binary pattern (LBP), gray level co-occurrence matrix (GLCM), and fuzzy color histogram (FCH) algorithms. The second proposed system uses pre-trained CNN models which are the GoogLeNet and AlexNet based on the extraction of deep feature maps and their classification with high accuracy. The third proposed method uses hybrid techniques consisting of two blocks: the first block of CNN models (GoogLeNet and AlexNet) to extract feature maps; the second block is the support vector machine (SVM) algorithm for classifying deep feature maps. The fourth proposed system uses ANN and FFNN based on the hybrid features between CNN models (GoogLeNet and AlexNet) and LBP, GLCM and FCH algorithms. All the proposed systems achieved superior results in diagnosing endoscopic images for the early detection of lower gastrointestinal diseases. All systems produced promising results; the FFNN classifier based on the hybrid features extracted by GoogLeNet, LBP, GLCM and FCH achieved an accuracy of 99.3%, precision of 99.2%, sensitivity of 99%, specificity of 100%, and AUC of 99.87%.

Bariatric surgery in the treatment of patients with obesity and type 1 diabetes: A retrospective study of clinical data.

AIM: To evaluate the effectiveness and safety of bariatric surgery in patients with coexisting type 1 diabetes and obesity who choose to undergo bariatric surgery for weight management. MATERIALS AND METHODS: We conducted a retrospective, longitudinal review of the clinical data of patients with type 1 diabetes, followed up at our centre after bariatric surgery had been performed elsewhere. RESULTS: Sixty-one patients were included, of whom 51% were women, and 57 (93%) were Emirati Arab, three (5%) were other Arab, and one (2%) was White in ethnic origin. The mean age at surgery was 31 years. A total of 42 patients (69%) underwent sleeve gastrectomy, 17 (28%) gastric bypass, and two (3%) gastric banding. In 48 patients with complete follow-up data, improvements were observed at 12 months in the median (interquartile range [IQR]) values for body mass index (BMI; 38.5 [34.9-40.9] to 26.1 [24.2-29.6] kg/m2 , P <0.001), glycated haemoglobin concentration (8.6 [7.8-9.2]% to 7.8 [7.2-8.5]%; P <0.001), daily insulin dose (1.0 [0.7-1.2] to 0.8 [0.6-0.9] units/kg/d; P <0.001), systolic blood pressure (127 [116-136] to 116 [110-120] mmHg; P <0.001), total cholesterol: high-density lipoprotein cholesterol ratio (3.4 [2.9-4.3] to 3.0 [2.6-3.5]; P <0.001), and albuminuria. In 32 patients followed up at 3 years, the median (IQR) reduction in BMI was 10.4 (5.9-11.7) kg/m2 , 50% reduced or stopped antihypertensive medication and 58% reduced or stopped lipid-modifying medication. Three patients each reported a single episode of diabetic ketoacidosis; in one case this was due to cessation of insulin treatment. CONCLUSIONS: In our cohort of patients with obesity and type 1 diabetes, bariatric surgery led to significant improvements in weight and cardiometabolic variables, with modest improvements in glycaemia. Few adverse events were reported.

Inhibition of jasmonate-mediated plant defences by the fungal metabolite higginsianin B.

Infection of Arabidopsis thaliana by the ascomycete fungus Colletotrichum higginsianum is characterized by an early symptomless biotrophic phase followed by a destructive necrotrophic phase. The fungal genome contains 77 secondary metabolism-related biosynthetic gene clusters, whose expression during the infection process is tightly regulated. Deleting CclA, a chromatin regulator involved in the repression of some biosynthetic gene clusters through H3K4 trimethylation, allowed overproduction of three families of terpenoids and isolation of 12 different molecules. These natural products were tested in combination with methyl jasmonate, an elicitor of jasmonate responses, for their capacity to alter defence gene induction in Arabidopsis. Higginsianin B inhibited methyl jasmonate-triggered expression of the defence reporter VSP1p:GUS, suggesting it may block bioactive jasmonoyl isoleucine (JA-Ile) synthesis or signalling in planta. Using the JA-Ile sensor Jas9-VENUS, we found that higginsianin B, but not three other structurally related molecules, suppressed JA-Ile signalling by preventing the degradation of JAZ proteins, the repressors of jasmonate responses. Higginsianin B likely blocks the 26S proteasome-dependent degradation of JAZ proteins because it inhibited chymotrypsin- and caspase-like protease activities. The inhibition of target degradation by higginsianin B also extended to auxin signalling, as higginsianin B treatment reduced auxin-dependent expression of DR5p:GUS. Overall, our data indicate that specific fungal secondary metabolites can act similarly to protein effectors to subvert plant immune and developmental responses.

Correction to: Efficacy of pulsed Nd:YAG laser in the treatment of patients with knee osteoarthritis: a randomized controlled trial.

The institutional affiliation of Dr. Aly Elsayed Mohamed Elsayed should be as follow.

Routine clinical use of liraglutide 3 mg for the treatment of obesity: Outcomes in non-surgical and bariatric surgery patients.

In this study we prospectively collected data on the use of liraglutide 3 mg in obese Arab patients. As part of routine care, 2092 patients were dispensed liraglutide 3 mg. Median age was 38 years and 77% were women. Median baseline weight was 95 kg and body mass index was 36.6 kg/m2 . Of the patients, 188 (9%) had previous bariatric surgery. Seven hundred and eighty-seven patients were treated for ≥16 weeks and their median (interquartile range) weight loss was 6.0 (2.4-9.4) kg, equivalent to 6.4% (2.6%-9.7%) of baseline weight (P < 0.0001, n = 787). Of those treated for ≥16 weeks, 474 (60%) achieved a weight loss of >5% of baseline weight while 182 (23%) achieved >10% weight loss. There was no difference in percentage weight loss between postbariatric surgery (n = 76) and non-surgical patients (n = 711). As a result of adverse events, mainly gastrointestinal symptoms, 140 (6.7%) of the patients stopped treatment. One patient developed acute pancreatitis in the context of gallstone disease but made an uneventful recovery. Liraglutide 3 mg was well tolerated and resulted in weight loss in routine clinical care similar to that seen in randomized controlled trials.

Chemical Activation of EDS1/PAD4 Signaling Leading to Pathogen Resistance in Arabidopsis.

In a chemical screen we identified thaxtomin A (TXA), a phytotoxin from plant pathogenic Streptomyces scabies, as a selective and potent activator of FLAVIN-DEPENDENT MONOOXYGENASE1 (FMO1) expression in Arabidopsis (Arabidopsis thaliana). TXA induction of FMO1 was unrelated to the production of reactive oxygen species (ROS), plant cell death or its known inhibition of cellulose synthesis. TXA-stimulated FMO1 expression was strictly dependent on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) and PHYTOALEXIN DEFICIENT4 (PAD4) but independent of salicylic acid (SA) synthesis via ISOCHORISMATE SYNTHASE1 (ICS1). TXA induced the expression of several EDS1/PAD4-regulated genes, including EDS1, PAD4, SENESCENCE ASSOCIATED GENE101 (SAG101), ICS1, AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) and PATHOGENESIS-RELATED PROTEIN1 (PR1), and accumulation of SA. Notably, enhanced ALD1 expression did not result in accumulation of the product pipecolic acid (PIP), which promotes FMO1 expression during biologically induced systemic acquired resistance. TXA treatment preferentially stimulated expression of PAD4 compared with EDS1, which was mirrored by PAD4 protein accumulation, suggesting that TXA leads to increased PAD4 availability to form EDS1-PAD4 signaling complexes. Also, TXA treatment of Arabidopsis plants led to enhanced disease resistance to bacterial and oomycete infection, which was dependent on EDS1 and PAD4, as well as on FMO1 and ICS1. Collectively, the data identify TXA as a potentially useful chemical tool to conditionally activate and interrogate EDS1- and PAD4-controlled pathways in plant immunity.

Efficacy of pulsed Nd:YAG laser in the treatment of patients with knee osteoarthritis: a randomized controlled trial.

The purpose of this study was to investigate the effects of pulsed Nd:YAG laser plus glucosamine/chondroitin sulfate (GCS) in patients with knee osteoarthritis (KOA) by examining changes in pain and knee function, as well as synovial thickness (ST) and femoral cartilage thickness (FCT). Sixty-seven male patients participated, with a mean (SD) age of 53.85 (4.39) years, weight of 84.01 (4.70) kg, height of 171.51 (3.96) cm, and BMI of 28.56 (1.22). Group 1 was treated with high-intensity laser therapy (HILT), GCS, and exercises (HILT + GCS + EX). Group 2 was treated with GCS plus exercises (GCS + EX), and group 3 received placebo laser plus exercises (PL + EX). The outcomes measured were pain level and functional disability using the visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. ST and FCT were measured by ultrasound examination. Statistical analyses were performed to compare differences between baseline and after 6 weeks of treatment and then after 3 months of follow-up. Statistical significance was set at p < 0.05. VAS and WOMAC were significantly decreased in all groups after 6 weeks, with nonsignificant differences between 6 weeks and 3 months of follow-up. ST was significantly decreased in the HILT + GCS + EX group posttreatment, with nonsignificant decreases in the GCS + EX and PL + EX groups, as well as nonsignificant differences to FCT in all groups. Overall, pulsed Nd:YAG laser combined with GCS and exercises was more effective than GCS + EX and exercises alone in the treatment of KOA patients.

Serum hepatocyte growth factor is associated with truncal fat mass and increased mortality in chronic kidney disease stage 5 patients with protein-energy wasting.

BACKGROUND: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis. METHODS: In 224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids. Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by subjective global assessment (SGA) were recorded at baseline. Patients were followed up for 5 years. RESULTS: Serum HGF levels were higher in patients with high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR: 2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL] than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI and non-PEW). Multivariate linear regression showed that TFMI was an independent predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high HGF and presence of PEW had worse all-cause mortality after adjusting for age, gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35). CONCLUSIONS: Increased TFMI was an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated HGF level increased the mortality risk in the presence of PEW. These results suggest a central role of HGF in the metabolic and nutritional alterations in CKD stage 5 patients.

Infarct Size Reduction in an Anterior ST-Elevation Myocardial Infarction Following "Optimized" Supersaturated Oxygen Therapy.

This comprehensive case report documents the treatment of a 37-year-old female patient who presented with anterior ST-elevation myocardial infarction (STEMI). The patient underwent percutaneous coronary intervention (PCI), followed by an innovative therapy - optimized supersaturated oxygen therapy (SSO2). This therapy was chosen due to its potential to enhance myocardial salvage, particularly in severe MI cases like the patient. The report meticulously details the patient's clinical course, including the diagnostic procedures and the rationale behind opting for SSO2 therapy. It highlights the significant improvements observed post-therapy: enhanced left ventricular (LV) function and a remarkable reduction in the size of the LV apical aneurysm. These outcomes suggest a direct benefit of SSO2 in reducing myocardial damage. Finally, the report discusses the broader implications of these findings. It underscores the potential of optimized SSO2 therapy in clinical settings, particularly for patients with anterior MI. The case exemplifies how advanced therapeutic interventions like SSO2 can play a pivotal role in improving clinical outcomes post-MI, thereby advocating for its consideration in similar clinical scenarios.

Handgrip strength and mortality in a cohort of kidney failure patients: Comparative analysis of different normalization methods.

OBJECTIVES: Reduced handgrip strength (HGS) is associated with adverse clinical outcomes. We analyzed and compared associations of HGS with mortality risk in dialysis patients, using different normalization methods of HGS. METHODS: HGS and clinical and laboratory parameters were measured in a cohort of 446 incident dialysis patients (median age 56 y, 62% men). The area under the receiver operating characteristic curve (AUROC) was used to compare different normalization methods of HGS as predictors of mortality: absolute HGS in kilograms; HGS normalized to height, weight, or body mass index; and HGS of a reference population of sex-matched controls (percentage of the mean HGS value [HGS%]). Multivariate linear regression analysis was used to assess HGS predictors. Competing risk regression analysis was used to evaluate 5-year all-cause mortality risk. Differences in survival time between HGS% tertiles were quantitated by analyzing the restricted mean survival time. RESULTS: The AUROC for HGS% was higher than the AUROCs for absolute or normalized HGS values. Compared with the high HGS% tertile, low HGS% (subdistribution hazard ratio [sHR] = 2.36; 95% CI, 1.19-3.70) and middle HGS% (sHR = 1.79; 95% CI, 1.12-2.74) tertiles were independently associated with higher all-cause mortality and those with high HGS% tertile survived on average 7.95 mo (95% CI, 3.61-12.28) and 18.99 mo (95% CI, 14.42-23.57) longer compared with middle and low HGS% tertile, respectively. CONCLUSIONS: HGS% was a strong predictor of all-cause mortality risk in incident dialysis patients and a better discriminator of survival than absolute HGS or HGS normalized to body size dimensions.

From theory to practice: An integrated TTF-UTAUT study on electric vehicle adoption behavior.

In Industry 4.0, the adoption of new technology has played a major role in the transportation sector, especially in the electric vehicles (EVs) domain. Nevertheless, consumer attitudes towards EVs have been difficult to gauge but researchers have tried to solve this puzzle. The prior literature indicates that individual attitudes and technology factors are vital to understanding users' adoption of EVs. Thus, the main aim is to meticulously investigate the unexplored realm of EV adoption within nations traditionally reliant on oil, exemplified by Saudia Arabia. By integrating the "task technology fit" (TTF) model and the "unified theory of acceptance and usage of technology" (UTAUT), this research develops and empirically validates the framework. A cross-section survey approach is adopted to collect 273 valid questionnaires from customers through convincing sampling. The empirical findings confirm that the integration of TTF and UTAUT positively promotes users' adoption of EVs. Surprisingly, the direct effect of TTF on behavioral intentions is insignificant, but UTAUT constructs play a significant role in establishing a significant relationship. Moreover, the UTAUT social influence factor has no impact on the EVs adoption. This groundbreaking research offers a comprehensive and holistic methodology for unravelling the complexities of EV adoption, achieved through the harmonious integration of two well-regarded theoretical frameworks. The nascent of this research lies in the skilful blending of technological and behavioral factors in the transportation sector.

Correction: From theory to practice: An integrated TTF-UTAUT study on electric vehicle adoption behavior.

[This corrects the article DOI: 10.1371/journal.pone.0297890.].

Exogenous glutathione protected wheat seedling from high temperature and water deficit damages.

High temperatures (HT) and drought are two major factors restricting wheat growth in the early growth stages. This study investigated the role of glutathione (GSH) amendment (0.0, 0.5, 1.0, and 2.0 mM) to soil in mitigating the adverse effect of HT (33 °C, with 25 °C as a control), water regimes (60% of field capacity and control), and their combinations. HT decreased the length, project area, surface area, volume, and forks of the root, while drought had the reverse effect. Shoot length, leaf area, leaf relative water content, and shoot and root dry matter were significantly decreased by HT and drought, and their combined impact was more noticeable. GSH significantly promoted the root system, shoot growth, and leaf relative water content. The combined treatment reduced chlorophyll a, chlorophyll b, and total chlorophyll. However, 0.5 mM GSH raised chlorophyll a, chlorophyll b, and total chlorophyll by 28.6%, 41.4%, and 32.5%, respectively, relative to 0.0 mM GSH. At combined treatment, 0.5 mM GSH decreased malondialdehyde (MDA) by 29.5% and increased soluble protein content by 24.1%. GSH meaningfully enhanced the activity of superoxide dismutase, catalase, and ascorbate peroxide in different treatments. This study suggested that GSH could protect wheat seedlings from the adverse effects of HT and/or drought stresses.

Flavonostilbenes natural hybrids from Rhamnoneuron balansae as potential antitumors targeting ALDH1A1: molecular docking, ADMET, MM-GBSA calculations and molecular dynamics studies.

Several studies have linked Cancer stem cells (CSCs) to cancer resistance development to chemotherapy and radiotherapy. ALDH1A1 is a key enzyme that regulates the gene expression of CSCs and creates an immunosuppressive tumor microenvironment. It was reported that quercetin and resveratrol were among the inhibitors of ALDH1A1. In early 2022, it was reported that new 11 flavonostilbenes (rhamnoneuronal D-N) were isolated from Rhamnoneuron balansae as potential antiaging natural products. Rhamnoneuronal H (5) could be envisioned as a natural hybrid of quercetin and resveratrol. It was therefore hypothesized that 5 and its analogous isolates rhamnoneuronal D-G (1-4) and rhamnoneuronal I-N (6-11) would have potential ALDH1A1 inhibitory activity. To this end, all isolates were subjected to molecular docking, MM-GBSA, ADMET, and molecular dynamics simulations studies to assess their potential as new leads for cancer treatment targeting ALDH1A1. In silico findings revealed that natural hybrid 5 has a similar binding affinity, judged by MM-GBSA, to the ALDH1A1 active site when compared to the co-crystalized ligand (-64.71 kcal/mole and -64.12 kcal/mole, respectively). Despite having lesser affinity than that of the co-crystalized ligand, the rest of the flavonostilbenes, except 2-4, displayed better binding affinities (-37.55 kcal/mole to -58.6 kcal/mole) in comparison to either resveratrol (-34.44 kcal/mole) or quercetin (-36.48 kcal/mole). Molecular dynamic simulations showed that the natural hybrids 1, 5-11 are of satisfactory stability up to 100 ns. ADMET outcomes indicate that these hybrids displayed acceptable properties and hence could represent an ideal starting point for the development of potent ALDH1A1 inhibitors for cancer treatment.Communicated by Ramaswamy H. Sarma.

Deep deterministic policy gradient algorithm: A systematic review.

Deep Reinforcement Learning (DRL) has gained significant adoption in diverse fields and applications, mainly due to its proficiency in resolving complicated decision-making problems in spaces with high-dimensional states and actions. Deep Deterministic Policy Gradient (DDPG) is a well-known DRL algorithm that adopts an actor-critic approach, synthesizing the advantages of value-based and policy-based reinforcement learning methods. The aim of this study is to provide a thorough examination of the latest developments, patterns, obstacles, and potential opportunities related to DDPG. A systematic search was conducted using relevant academic databases (Scopus, Web of Science, and ScienceDirect) to identify 85 relevant studies published in the last five years (2018-2023). We provide a comprehensive overview of the key concepts and components of DDPG, including its formulation, implementation, and training. Then, we highlight the various applications and domains of DDPG, including Autonomous Driving, Unmanned Aerial Vehicles, Resource Allocation, Communications and the Internet of Things, Robotics, and Finance. Additionally, we provide an in-depth comparison of DDPG with other DRL algorithms and traditional RL methods, highlighting its strengths and weaknesses. We believe that this review will be an essential resource for researchers, offering them valuable insights into the methods and techniques utilized in the field of DRL and DDPG.

Region-wise evaluation of price-based demand response programs in Japan's wholesale electricity market considering microeconomic equilibrium.

Real-time pricing demand response programs (RTP-DRPs) are practical measures that ensure the end user's profitability from using electricity by adjusting the supply and demand equilibrium without activating costly solutions. This study explores the potential of RTP-DRPs by developing and applying a region-wise modeling approach based on maximizing the end user's social welfare in the wholesale electricity market in Japan. The regions of the wholesale market are classified based on their response into regions with excess supply, regions with high demand burden, and regular suppliers of inter-regional connections. The results revealed that the RTP-DRPs could potentially reduce the peak demand of the residential sector in Chubu, Chugoku, Kansai, Kyushu, Tokyo, and Tohoku by 1.91%-7.81%. Meanwhile, in Hokkaido, Hokuriku, and Shikoku, by 16.13%-22.9%. The avoided greenhouse emission (GHG) in Tokyo is estimated to be 82.6 and 192.2 tons in summer and winter, respectively.

Dehiscent Prosthetic Aortic Valve and Aortic Root Pseudoaneurysm Complicated by Left Main Coronary Artery Compression.

Prosthetic aortic valve dehiscence is an uncommon complication of prosthetic valve endocarditis that may occur in patients who have undergone aortic valve replacement (AVR). The concurrent presence of aortic root pseudoaneurysm may further complicate the clinical presentation through the external compression of coronary arteries. Thus, patients may present with clinical features of coronary ischemia. Echocardiogram and coronary angiography are useful in establishing diagnosis. Treatment involves a multidisciplinary approach involving cardiologists, infectious disease specialists, and cardiothoracic surgeons. The authors of this study discuss a 51-year-old male who presented with anginal chest pain and was found to have a new left bundle branch block, elevated troponins, and left main coronary artery compression complicating aortic root aneurysm. He ended up requiring a re-do AVR, repair of the pseudoaneurysm, and coronary artery bypass graft.