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.

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.

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.

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.

Outcomes of patients with cardiac amyloidosis undergoing percutaneous left atrial appendage occlusion.

BACKGROUND: There is limited data on the safety and efficacy of left atrial appendage occlusion (LAAO) devices in patients with cardiac amyloidosis. We examined the outcomes of patients with cardiac amyloidosis undergoing LAAO device implantation in a nationally representative cohort of patients. METHODS: The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with atrial fibrillation (AF) undergoing LAAO. Patients were divided into those with cardiac amyloidosis and those without cardiac amyloidosis. A multivariable logistic regression model was utilized to assess the independent association of cardiac amyloidosis with in-hospital, 30-day/90-day/180-day outcomes after adjusting for confounders. RESULTS: Our cohort included 54,900 LAAO implantation procedures, of which 220 (0.4%) had cardiac amyloidosis. Patients with cardiac amyloidosis had a lower proportion of women and a lower prevalence of comorbidities including anemia, obesity, diabetes, and peripheral vascular disorders but a higher prevalence of stroke, as compared to those without cardiac amyloidosis. On multivariable analysis, cardiac amyloidosis was associated with significantly higher odds of peri-procedural major adverse events (adjusted odds ratio [aOR]: 2.69; 95% confidence interval [CI]: 1.41-5.14; p<0.01) and neurological complications (aOR: 5.48; 95% CI: 2.47-12.8; p<0.01). There was no difference in the odds of other peri-procedural complications, in-hospital mortality, hospital resource utilization, and 30/90/180-day all-cause/bleeding/stroke-related readmissions between both groups. CONCLUSION: Patients with cardiac amyloidosis undergoing LAAO device implantation have an increased risk of peri-procedural complications without any difference in bleeding/stroke-related readmissions. These hypothesis-generating findings need validation in future prospective studies.

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.

Optimal weighting factor design based on entropy technique in finite control set model predictive torque control for electric drive applications.

In the conventional finite control set model predictive torque control, the cost function consists of different control objectives with varying units of measurements. Due to presence of diverse variables in cost function, weighting factors are used to set the relative importance of these objectives. However, selection of these weighting factors in predictive control of electric drives and power converters still remains an open research challenge. Improper selection of weighting factors can lead to deterioration of the controller performance. This work proposes a novel weighting factor tuning method based on the Multi-Criteria-Decision-Making (MCDM) technique called the Entropy method. This technique has several advantages for multi-objective problem optimization. It provides a quantitive approach and incorporates uncertainties and adaptability to assess the relative importance of different criteria or objectives. This technique performs the online tuning of the weighting factor by forming a data set of the control objectives, i.e., electromagnetic torque and stator flux magnitude. After obtaining the error set of control variables, the objective matrix is normalized, and the entropy technique is applied to design the corresponding weights. An experimental setup based on the dSpace dS1104 controller is used to validate the effectiveness of the proposed method for a two-level, three-phase voltage source inverter (2L-3P) fed induction motor drive. The dynamic response of the proposed technique is compared with the previously proposed MCDM-based weighting factor tuning technique and conventional MPTC. The results reveal that the proposed method provides an improved dynamic response of the drive under changing operating conditions with a reduction of 28% in computational burden and 38% in total harmonic distortion, respectively.

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.

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Temporal and regional trends in adults with diabetics kidney disease in the US from 1999 to 2020.

AIMS: We aim to analyze trends in mortality rates among adults with diabetic kidney disease (DKD) in the US from 1999 to 2020. METHODS: We queried the Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research database for mortality statistics from 1999 to 2020 associated with DKD in adults aged ≥25 years. Age-adjusted mortality rates (AAMRs) were calculated and trends were analyzed using the Joinpoint Regression Program. RESULTS: From 1999 to 2020, a total of 528,430 deaths were reported among adults with DKD. The mortality rates increased over time with males consistently exhibiting higher AAMR than females. NH American Indian or Alaska Native individuals had the highest AAMR, followed by NH Blacks, Hispanics, NH Whites, and NH Asians. The West region had the highest AAMR, followed by the Midwest, South, and Northeast. Rural regions had higher AAMR than urban areas, and mortality rates increased with age. CONCLUSIONS: This study reveals notable disparities in DKD mortality rates across demographic groups and geographic regions. NH American Indians or Alaska Natives, males, elderly individuals, rural residents, and those in the West region were disproportionately affected. Understanding these trends is crucial for developing targeted interventions to reduce DKD-related mortality and address healthcare disparities.

Morphometric and molecular characterization of Channa marulius from Riverine system of Punjab, Pakistan.

OBJECTIVE: Channidae family, are major freshwater fish species amongst the local aquatic fauna of Pakistan, while, there is limited availability of local data on their molecular identification and phylogenetic analysis. METHODS: Channa species were collected from four different geographical sites in the tertiary of Punjab province on the Indus and Chenab rivers of Pakistan. Morphometric records and molecular techniques were used to determine the intraspecific variations among populations of Channa marulius. Mitochondrial DNA was extracted from the flesh of C. marulius, while, COI gene was used for molecular identification and variation levels were estimated by using Principal Component Analysis. RESULTS: Data recorded on the basis of morphometric parameters clearly divided the C. marulius of different locations into two distinct categories, which accounted for a cumulative variability of 97.6%. Non-significance (P < 0.05) among the C. marulius showed that it contains a unique control haplotype localized within the sub-population. The intra-species distance ranged from 0.000 to 0.001 for four different populations, in contrast, the sequences retrieved from the NCBI database exhibited a range span of 0.000-0.003, while, sequence diversity ranged from 0.000 to 0.006 for this intra-specific comparison. The cladogram was also constructed for C. marulius of different geographical locations for observation of phylogenetic relationship. The conclusion drawn from the phylogenetic analysis of C. marulius populations used in this study, contributes significantly to the understanding of genetic variations within populations of this species. The findings provide valuable insight to devise conservation strategies in fisheries management programs in Pakistan.

Computational study of effect of hybrid nanoparticles on hemodynamics and thermal transfer in ruptured arteries with pathological dilation.

The intended research aims to explore the convection phenomena of a hybrid nanofluid composed of gold and silver nanoparticles. This research is novel and significant because there is a lack of existing studies on the flow behavior of hybrid nanoparticles with important physical properties of blood base fluids, especially in the case of sidewall ruptured dilated arteries. The implementation of combined nanoparticles rather than unadulterated nanoparticles is one of the most crucial elements in boosting the thermal conduction of fluids. The research methodology encompasses the utilization of advanced bio-fluid dynamics software for simulating the flow of the nanofluid. The physical context elucidates the governing equations of momentum, mass, momentum, and energy in terms of partial differential equations. The results are displayed in both tabular and graphical forms to demonstrate the numerical and graphical solutions. The effect of physical parameters on velocity distribution is illustrated through graphs. Furthermore, the study's findings are unique and original, and these computational discoveries have not been published by any researcher before. The finding implies that utilizing hybrid nanoparticles as drug carriers holds great promise in mitigating the effects of blood flow, potentially enhancing drug delivery, and minimizing its impact on the body.

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.

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

Soliton dynamics and nonlinear phenomena in quantum deformation has been investigated through conformal time differential generalized form of q deformed Sinh-Gordon equation. The underlying equation has recently undergone substantial amount of research. In Phase 1, we employed modified auxiliary and new direct extended algebraic methods. Trigonometric, hyperbolic, exponential and rational solutions are successfully extracted using these techniques, coupled with the best possible constraint requirements implemented on parameters to ensure the existence of solutions. The findings, then, are represented by 2D, 3D and contour plots to highlight the various solitons' propagation patterns such as kink-bright, bright, dark, bright-dark, kink, and kink-peakon solitons and solitary wave solutions. It is worth emphasizing that kink dark, dark peakon, dark and dark bright solitons have not been found earlier in literature. In phase 2, the underlying model is examined under various chaos detecting tools for example lyapunov exponents, multistability and time series analysis and bifurcation diagram. Chaotic behavior is investigated using various initial condition and novel results are obtained.

Pericardial effusion requiring intervention in patients undergoing leadless pacemaker implantation: A real-world analysis from the National Inpatient Sample database.

Background: Pericardial effusion requiring percutaneous or surgical-based intervention remains an important complication of a leadless pacemaker implantation. Objective: The study sought to determine real-world prevalence, risk factors, and associated outcomes of pericardial effusion requiring intervention in leadless pacemaker implantations. Methods: The National Inpatient Sample and International Classification of Diseases-Tenth Revision codes were used to identify patients who underwent leadless pacemaker implantations during the years 2016 to 2020. The outcomes assessed in our study included prevalence of pericardial effusion requiring intervention, other procedural complications, and in-hospital outcomes. Predictors of pericardial effusion were also analyzed. Results: Pericardial effusion requiring intervention occurred in a total of 325 (1.1%) leadless pacemaker implantations. Patient-level characteristics that predicted development of a serious pericardial effusion included >75 years of age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75), female sex (OR 2.03, 95% CI 1.62-2.55), coagulopathy (OR 1.50, 95% CI 1.12-1.99), chronic pulmonary disease (OR 1.36, 95% CI 1.07-1.74), chronic kidney disease (OR 1.53, 95% CI 1.22-1.94), and connective tissue disorders (OR 2.98, 95% CI 2.02-4.39). Pericardial effusion requiring intervention was independently associated with mortality (OR 5.66, 95% CI 4.24-7.56), prolonged length of stay (OR 1.36, 95% CI 1.07-1.73), and increased cost of hospitalization (OR 2.49, 95% CI 1.92-3.21) after leadless pacemaker implantation. Conclusion: In a large, contemporary, real-world cohort of leadless pacemaker implantations in the United States, the prevalence of pericardial effusion requiring intervention was 1.1%. Certain important patient-level characteristics predicted development of a significant pericardial effusion, and such effusions were associated with adverse outcomes after leadless pacemaker implantations.

Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and therapeutic targets for preterm birth.

Background: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are intricately linked with specific maternal health conditions, exhibit shared placental abnormalities, and play pivotal roles in precipitating preterm birth (PTB) incidences. However, the molecular mechanism underlying the association between PE and IUGR has not been determined. Therefore, we aimed to analyze the data of females with PE and those with PE + IUGR to identify the key gene(s), their molecular pathways, and potential therapeutic interactions. Methods: In this study, a comprehensive relationship analysis of both PE and PE + IUGR was conducted using RNA sequence datasets. Using two datasets (GSE148241 and GSE114691), differential gene expression analysis via DESeq2 through R-programming was performed. Gene set enrichment analysis was performed using ClusterProfiler, protein‒protein interaction (PPI) networks were constructed, and cluster analyses were conducted using String and MCODE in Cytoscape. Functional enrichment analyses of the resulting subnetworks were performed using ClueGO software. The hub genes were identified under both conditions using the CytoHubba method. Finally, the most common hub protein was docked against a library of bioactive flavonoids and PTB drugs using the PyRx AutoDock tool, followed by molecular dynamic (MD) simulation analysis. Pharmacokinetic analysis was performed to determine the ADMET properties of the compounds using pkCSM. Results: We identified eight hub genes highly expressed in the case of PE, namely, PTGS2, ENG, KIT, MME, CGA, GAPDH, GPX3, and P4HA1, and the network of the PE + IUGR gene set demonstrated that nine hub genes were overexpressed, namely, PTGS2, FGF7, FGF10, IL10, SPP1, MPO, THBS1, CYBB, and PF4. PTGS2 was the most common hub gene found under both conditions (PE and PEIUGR). Moreover, the greater (-9.1 kcal/mol) molecular binding of flavoxate to PTGS2 was found to have satisfactory pharmacokinetic properties compared with those of other compounds. The flavoxate-bound PTGS2 protein complex remained stable throughout the simulation; with a ligand fit to protein, i.e., a RMSD ranging from ∼2.0 to 4.0 Å and a RMSF ranging from ∼0.5 to 2.9 Å, was observed throughout the 100 ns analysis. Conclusion: The findings of this study may be useful for treating PE and IUGR in the management of PTB.