SwissADME studies and Density Functional Theory (DFT) approaches of methyl substituted curcumin derivatives.

Research suggests curcumin's safety and efficacy, prompting interest in its use for treating and preventing various human diseases. The current study aimed to predict drag ability of methyl substituted curcumin derivatives (BL1 to BL4) using SwissADME and Density Functional Theory (DFT) approaches. The curcumin derivatives investigated mostly adhere to Lipinski's rule of five, with molecular properties including MW, F. Csp3, nHBA, nHBD, and TPSA falling within acceptable limits. The compounds demonstrating high lipophilicity while poor water solubility. The pharmacokinetic evaluation revealed favorable gastrointestinal absorption and blood-brain barrier permeation while none were identified as substrates for P-glycoprotein, however, revealed inhibitory actions against various cytochrome P450 enzymes. Additionally, all derivatives exhibited a consistent bioavailability score of 0.55. Similarly, the DFT computations of the compounds of the curcumin derivatives were conducted at B3LYP/6-311 G** level to predict and then assess the key electronic characteristics underlying the bioactivity. Accordingly, the BL4 molecule (ΔEgap= 4.105 eV) would prefer to interact with the external molecular system more than the other molecules due to having the biggest energy gap. The ΔNmax (2.328 eV) and Δεback-donat. (-0.446 eV) scores implied that BL1 would have more charge transfer capability and the lowest stability via back donation among the compounds. In short, the derivative (BL1 to BL4) exhibited strong extrinsic therapeutic properties and therefore stand eligible for further in vitro and in vivo studies.

Immuno-Haematologic Aspects of Dengue Infection: Biologic Insights and Clinical Implications.

Dengue infection is caused by the dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries, with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease, which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormalities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research.

Correction: Computation of soliton structure and analysis of chaotic behaviour in quantum deformed Sinh-Gordon model.

[This corrects the article DOI: 10.1371/journal.pone.0304424.].

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Ranitidine degradation in layered double hydroxide activated peroxymonosulfate system: impact of transition metal composition and reaction mechanisms.

Ranitidine, a competitive inhibitor of histamine H2 receptors, has been identified as an emerging micropollutant in water and wastewater, raising concerns about its potential impact on the environment and human health. This study aims to address this issue by developing an effective removal strategy using two types of layered double hydroxide (LDH) catalysts (i.e., CoFeLDH and CoCuLDH). Characterization results show that CoFeLDH catalyst has superior catalytic properties due to its stronger chemical bond compared to CoCuLDH. The degradation experiment shows that 100% degradation of ranitidine could be achieved within 20 min using 25 mg/L of CoFeLDH and 20 mg/L of peroxymonosulfate (PMS). On the other hand, CoCuLDH was less effective, achieving only 70% degradation after 60 min at a similar dosage. The degradation rate constant of CoFeLDH was 10 times higher than the rate constant of CoCuLDH at different pH range. Positive zeta potential of CoFeLDH made it superior over CoCuLDH regarding catalytic oxidation of PMS. The catalytic degradation mechanism shows that sulfate radicals played a more dominant role than hydroxyl radicals in the case of LDH catalysts. Also, CoFeLDH demonstrated a stronger radical pathway than CoCuLDH. XPS analysis of CoFeLDH revealed the cation percentages at different phases and proved the claim of being reusable even after 8 cycles. Overall, the findings suggest that CoFeLDH/PMS system proves to be a suitable choice for attaining high degradation efficiency and good stability in the remediation of ranitidine in wastewater.

ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities.

Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial/ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the AACR Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; p < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic whites in adjusted models (OR = 2.52, 95%CI = 1.20-5.33, p = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.

Unravelling reference bias in ancient DNA datasets.

MOTIVATION: The alignment of sequencing reads is a critical step in the characterization of ancient genomes. However, reference bias and spurious mappings pose a significant challenge, particularly as cutting-edge wet lab methods generate datasets that push the boundaries of alignment tools. Reference bias occurs when reference alleles are favoured over alternative alleles during mapping, whereas spurious mappings stem from either contamination or when endogenous reads fail to align to their correct position. Previous work has shown that these phenomena are correlated with read length but a more thorough investigation of reference bias and spurious mappings for ancient DNA has been lacking. Here, we use a range of empirical and simulated palaeogenomic datasets to investigate the impacts of mapping tools, quality thresholds, and reference genome on mismatch rates across read lengths. RESULTS: For these analyses, we introduce AMBER, a new bioinformatics tool for assessing the quality of ancient DNA mapping directly from BAM-files and informing on reference bias, read length cut-offs and reference selection. AMBER rapidly and simultaneously computes the sequence read mapping bias in the form of the mismatch rates per read length, cytosine deamination profiles at both CpG and non-CpG sites, fragment length distributions, and genomic breadth and depth of coverage. Using AMBER, we find that mapping algorithms and quality threshold choices dictate reference bias and rates of spurious alignment at different read lengths in a predictable manner, suggesting that optimized mapping parameters for each read length will be a key step in alleviating reference bias and spurious mappings. AVAILABILITY AND IMPLEMENTATION: AMBER is available for noncommercial use on GitHub (https://github.com/tvandervalk/AMBER.git). Scripts used to generate and analyse simulated datasets are available on Github (https://github.com/sdolenz/refbias_scripts).

Beyond Shell-Filling: Strong Enhancement of Electron Affinity of Metal Clusters through a Noninvasive Oriented External Electric Field.

Traditional electron counting rules, like the Jellium model, have long been successfully utilized in designing superhalogens by modifying clusters to have one electron less than a filled electronic shell. However, this shell-filling approach, which involves altering the intrinsic properties of the clusters, can be complex and challenging to control, especially in experiments. In this letter, we theoretically establish that the oriented external electric field (OEEF) can substantially enhance the electron affinity (EA) of diverse aluminum-based metal clusters with varying valence electron configurations, leading to the creation of superhalogen species without altering their shell arrangements. This OEEF approach offers a noninvasive alternative to traditional superatom design strategies, as it does not disrupt the clusters' geometrical structures and superatomic states. These findings contribute a vital piece to the puzzle of constructing superalkalis and superhalogens, extending beyond conventional shell-filling strategies and potentially expanding the range of applications for functional clusters.

Advances in MXene-based technologies for the remediation of toxic phenols: A comprehensive review.

The pressing global issue of organic pollutants, particularly phenolic compounds derived primarily from industrial wastes, poses a significant threat to the environment. Although progress has been made in the development of low-cost materials for phenolic compound removal, their effectiveness remains limited. Thus, there is an urgent need for novel technologies to comprehensively address this issue. In this context, MXenes, known for their exceptional physicochemical properties, have emerged as highly promising candidates for the remediation of phenolic pollutants. This review aims to provide a comprehensive and critical evaluation of MXene-based technologies for the removal of phenolic pollutants, focusing on the following key aspects: (1) The classification and categorization of phenolic pollutants, highlighting their adverse environmental impacts, and emphasizing the crucial need for their removal. (2) An in-depth discussion on the synthesis methods and properties of MXene-based composites, emphasizing their suitability for environmental remediation. (3) A detailed analysis of MXene-based adsorption, catalysis, photocatalysis, and hybrid processes, showcasing current advancements in MXene modification and functionalization to enhance removal efficiency. (4) A thorough examination of the removal mechanisms and stability of MXene-based technologies, elucidating their operating conditions and stability in pollutant removal scenarios. (5) Finally, this review concludes by outlining future challenges and opportunities for MXene-based technologies in water treatment, facilitating their potential applications. This comprehensive review provides valuable insights and innovative ideas for the development of versatile MXene-based technologies tailored to combat water pollution effectively.

Exploring optical solitary wave solutions in the (2+1)-dimensional equation with in-depth of dynamical assessment.

The current study explores the (2+1)-dimensional Chaffee-Infante equation, which holds significant importance in theoretical physics renowned reaction-diffusion equation with widespread applications across multiple disciplines, for example, ion-acoustic waves in optical fibres, fluid dynamics, electromagnetic wave fields, high-energy physics, coastal engineering, fluid mechanics, plasma physics, and various other fields. Furthermore, the Chaffee-Infante equation serves as a model that elucidates the physical processes of mass transport and particle diffusion. We employ an innovative new extended direct algebraic method to enhance the accuracy of the derived exact travelling wave solutions. The obtained soliton solutions span a wide range of travelling waves like bright-bell shape, combined bright-dark, multiple bright-dark, bright, flat-kink, periodic, and singular. These solutions offer valuable insights into wave behaviour in nonlinear media and find applications in diverse fields such as optical fibres, fluid dynamics, electromagnetic wave fields, high-energy physics, coastal engineering, fluid mechanics, and plasma physics. Soliton solutions are visually present by manipulating parameters using Wolfram Mathematica software, graphical representations allow us to study solitary waves as parameters change. Observing the dynamics of the model, this study presents sensitivity in a nonlinear dynamical system. The applied mathematical approaches demonstrate its ability to identify reliable and efficient travelling wave solitary solutions for various nonlinear evolution equations.

Impact of Race and Ethnicity on Outcomes after Umbilical Cord Blood Transplantation.

BACKGROUND: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. OBJECTIVE: To compare outcomes by social determinants of health. STUDY DESIGN: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N=1752) or reduced intensity conditioning (N=759) for Acute Myeloid Leukemia, Acute Lymphoid Leukemia, or Myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). RESULTS: For 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6-45.3) for Whites, 36.1% (99% CI, 28.2-44.5) for Latinx, 45.8% (99% CI, 36.7-55.1) for Blacks, and 44.5% (99% CI, 33.6-55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p=0.0005, HR 1.45, 99% CI 1.18-1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7-72.2) for Whites, 57.1% (99%CI, 49-64.9) for Latinx, 46.8% (99%CI, 35.3-58.4) for Blacks, and 53.8% (99%CI, 32.7-74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = 0.051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p= 0.0016, HR 2.25, 99% CI 1.36-3.74) and Latinx (p= 0.0016, HR 2.17, 99% CI 1.43-3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults. Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p =0.03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p=0.02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p=0.02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. CONCLUSIONS: OS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

The Acute Impact of Propofol on Blood-Brain Barrier Integrity in Mice.

PURPOSE: We investigated whether short term infusion of propofol, a highly lipophilic agonist at GABAA receptors, which is in widespread clinical use as anesthetic and sedative, affects passive blood-brain barrier (BBB) permeability in vivo. METHODS: Mice were anesthetized with an intraperitoneal injection of ketamine/xylazine followed by a continuous IV infusion of propofol in lipid emulsion through a tail vein catheter. Control groups received ketamine/xylazine anesthesia and an infusion of Intralipid, or ketamine/xylazine anesthesia only. [13C12]sucrose as a permeability marker was injected as IV bolus 15 min after start of the infusions. Brain uptake clearance, Kin, of sucrose was calculated from the brain concentrations at 30 min and the area under the plasma-concentration time curve. We also measured the plasma and brain concentration of propofol at the terminal time point. RESULTS: The Kin value for propofol-infused mice was significantly higher, by a factor of 1.55 and 1.87, compared to the Intralipid infusion and the ketamine/xylazine groups, respectively, while the control groups were not significantly different. No difference was seen in the expression levels of tight junction proteins in brain across all groups. The propofol plasma concentration at the end of infusion (10.7 µM) matched the clinically relevant range of blood concentrations reported in humans, while concentration in brain was 2.5-fold higher than plasma. CONCLUSIONS: Propofol at clinical plasma concentrations acutely increases BBB permeability, extending our previous results with volatile anesthetics to a lipophilic injectable agent. This prompts further exploration, potentially refining clinical practices and ensuring safety, especially during extended propofol infusion schemes.

Improving self-dependency in Pakistan: Experience of a locally prepared automated PD machine.

The increasing burden of haemodialysis on healthcare systems merits efforts to make peritoneal dialysis (PD) more accessible to the population in need of kidney replacement therapy. Automated PD (APD) may be a suitable alternative to continuous ambulatory peritoneal dialysis for home dialysis especially for children, elderly and patients who lead a busy schedule in their jobs thus leaving more time for personal and family activities during the day. Recently, a local bioengineering company took the initiative to develop a locally manufactured, low-cost APD cycler in Pakistan, with an aim to improve the self-dependency and home-based kidney replacement therapy. We herein present our first experience of APD on this locally manufactured APD cycler. It was an investigator-led study on the utility of a locally manufactured APD cycler and the safety and efficacy of the standard operating procedures developed and adopted by the study authors. A total of eight patients agreed to participate in this study extending from September 2021 to August 2022. There were four male and four female patients, and the mean age was 52.5 + 19.71 years. The locally manufactured cycler provided more than 1600 h of APD sessions. The APD sessions were well tolerated with only a few instances of minor mechanical and software issues that did not require termination of therapy. There were no episodes of peritonitis; however, one of the patients had an episode of exit site and tunnel infection that did not seem to be related to the procedure. Our experience with locally manufactured APD cycler was successful and without major adverse events. We believe the locally produced APD cycler is a viable cost-effective option for patients requiring PD and may herald a new era of self-dependency for patients considering or undergoing PD in Pakistan.

Normotensive metabolic syndrome in mice deleted of the gene, Type 1 transient receptor potential canonical channel.

Metabolic syndrome has become a global epidemic, affecting all developed countries/communities with growing economies. Worldwide, increasing efforts have been directed at curbing this growing problem. Mice deleted of the gene encoding Type 1 Transient Receptor Potential Canonical Channel (Trpc1) were found to weigh heavier than controls. They had fasting hyperglycemia and impaired glucose tolerance vs. wild type controls. Beyond 1 year of age, plasma triglyceride level in null mice was elevated. Plasma cholesterol tended to be higher than controls. Livers in null mice were heavier, richer in triglyceride, and more echogenic vs. controls on ultrasound evaluation. Hematocrit was lower in null mice of both genders beginning at 2nd/3rd month of age in the absence of bleeding/ hemolysis. Measured by indirect tail-cuff method or by the direct arterial cannulation, blood pressures in null mice were lower than controls. We conclude that Trpc1 gene regulates body metabolism and that except for hypertension, phenotypes of mice after deletion of the Trpc1 gene resemble the metabolic syndrome, suggesting that this could be a good experimental model for future investigation on the pathogenesis and management of this disorder.

Efficacy and Safety of Rivaroxaban Versus Enoxaparin in Prevention of Recurrence of Venous Thrombo-Embolism Events in Cancer Patients: A Meta-Analysis.

OBJECTIVE: To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism. METHODS: A search of Pub Med, Scopus, and Google Scholar, from inception through April 2023 was conducted. Articles comparing rivaroxaban with enoxaparin in patients with cancer and VTE/PE/DVT were included. Review Manager Version 5.2 was utilised for the analysis of the following outcomes; VTE, PE, DVT, major bleeding, and mortality. RESULTS: A total of 8 articles and 2276 patients were included in the final analysis. Pooled analysis showed that rivaroxaban had a statistically insignificant reduced association with VTE occurrence (RR:0.83, 95% CI:0.58-1.18, P:0.3) as well as a statically insignificant reduction in major bleeding (RR:0.79, 95% CI:0.53-1.18, P:0.25). Analysis showcased that there was an insignificant reduction of mortality rivaroxaban as compared to enoxaparin (RR:0.74, 95% CI: 0.46-1.20, P:0.23). CONCLUSION: Rivaroxaban can serve as a viable alternative to enoxaparin, with no appreciable drawbacks, for preventing and managing VTE in patients with malignancy.

Global Analysis of RTS, S/AS01 Malaria Vaccine Acceptance Rates and Influencing Factors: A Systematic Review.

Malaria remains a significant global health challenge, with Plasmodium parasites transmitted by Anopheles mosquitoes causing substantial morbidity and mortality. Despite historical efforts, malaria continues to affect millions worldwide, particularly in tropical regions. This systematic review aimed to assess the acceptability of the RTS, S/AS01 malaria vaccine among diverse populations. A comprehensive search strategy was employed across databases such as Cochrane Library, Embase, Google Scholar, and Medline. Studies were included based on specific criteria, including observational and cross-sectional designs involving adults. Data extraction and analysis were conducted meticulously, encompassing key variables related to vaccine acceptance rates and influencing factors. Analysis of 18 studies involving 18,561 participants revealed an overall malaria vaccine acceptance rate of 87.51%, ranging from 32.26% to 99.30%. Significant variations were observed based on demographics, with Ghana and Nigeria reporting high acceptance rates. Factors influencing acceptance included knowledge levels, past vaccination experiences, community preferences, and engagement in malaria prevention behaviors. Concerns about adverse reactions and regional disparities were noted as potential barriers to acceptance. This review highlights the importance of understanding public perceptions and concerns regarding malaria vaccines to enhance vaccine coverage and uptake. Tailored communication strategies, advocacy efforts, and targeted education interventions are crucial for addressing misconceptions and increasing vaccine acceptance. Policy recommendations should consider demographic and regional factors to ensure effective implementation of malaria vaccination programs, ultimately contributing to global malaria prevention efforts and public health initiatives.

Navigating the future of solid oxide fuel cell: Comprehensive insights into fuel electrode related degradation mechanisms and mitigation strategies.

Solid Oxide Fuel Cells (SOFCs) have proven to be highly efficient and one of the cleanest electrochemical energy conversion devices. However, the commercialization of this technology is hampered by issues related to electrode performance degradation. This article provides a comprehensive review of the various degradation mechanisms that affect the performance and long-term stability of the SOFC anode caused by the interplay of physical, chemical, and electrochemical processes. In SOFCs, the most used anode material is nickel-yttria stabilized zirconia (Ni-YSZ) due to its advantages of high electronic conductivity and high catalytic activity for H2 fuel. However, various factors affecting the long-term stability of the Ni-YSZ anode, such as redox cycling, carbon coking, sulfur poisoning, and the reduction of the triple phase boundary length due to Ni particle coarsening, are thoroughly investigated. In response, the article summarizes the state-of-the-art diagnostic tools and mitigation strategies aimed at improving the long-term stability of the Ni-YSZ anode.