Priorities for Clinical Research in Pediatric Extracorporeal Membrane Oxygenation Anticoagulation From the Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To identify and prioritize research questions for anticoagulation and hemostasis management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus. DATA SOURCES: Systematic review was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial consensus conferences of international, interprofessional experts in the management of ECMO for critically ill neonates and children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill neonates and children. DATA EXTRACTION: Within each of the eight subgroups, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: Following the systematic review of MEDLINE, EMBASE, and Cochrane Library databases from January 1988 to May 2021, and the consensus process for clinical recommendations and consensus statements, PEACE panel experts constructed research priorities using the Child Health and Nutrition Research Initiative methodology. Twenty research topics were prioritized, falling within five domains (definitions and outcomes, therapeutics, anticoagulant monitoring, protocolized management, and impact of the ECMO circuit and its components on hemostasis). CONCLUSIONS: We present the research priorities identified by the PEACE expert panel after a systematic review of existing evidence informing clinical care of neonates and children managed with ECMO. More research is required within the five identified domains to ultimately inform and improve the care of this vulnerable population.

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference.

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.

The Influence of the Extracorporeal Membrane Oxygenation Circuit and Components on Anticoagulation Management: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: Management of ECMO anticoagulation in the setting of different ECMO circuit components. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented. CONCLUSIONS: The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.

Transcatheter Axial Pump Use in Pediatric Patients on Veno-Arterial Extracorporeal Membrane Oxygenation: An ACTION Collaborative Experience.

We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Utilizing the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) collaborative database, we conducted a retrospective, multicenter study of all patients with cardiogenic shock requiring VA-ECMO support with subsequent Impella implant between October 2014 and December 2021. The primary outcome was defined as death while on Impella support. Secondary outcomes were recovery, transplantation, and transition to durable ventricular assist device (VAD) at the time of Impella explantation. Adverse events were defined according to the ACTION registry criteria. Twenty subjects were supported with Impella; Impella 2.5 (n = 3), CP (n = 12), 5.0/5.5 (n = 5). The median Interquartile range (IQR) age, weight, and body surface area at implantation were 15.6 years (IQR = 13.9-17.2), 65.7 kg (IQR = 53.1-80.7), and 1.74 m2 (IQR = 1.58-1.98). Primary cardiac diagnoses were dilated cardiomyopathy/myocarditis in nine (45%), congenital heart disease in four (20%), graft failure/rejection in four (20%), and three (15%) others. Most common adverse events included hemolysis (50%) and bleeding (20%). There were two deaths (10%) in the cohort. Nine patients (45%) were explanted for recovery, eight (40%) were transitioned to a durable VAD, and one (5%) underwent heart transplantation. Impella percutaneous pump support should be considered in the older pediatric population supported with peripheral VA-ECMO, as a means of left heart decompression, and a strategy to come off ECMO to achieve endpoints of myocardial recovery, transition to a durable VAD, or transplantation.

Performance and environmental sustainability studies on a dual-fuel IC engine working with producer gas of variable calorific values from rural biomass.

Decentralized power generation using renewable gaseous biofuels faces challenges due to their inconsistent quality and availability. Mixing producer gas (PG) with diesel as a secondary fuel is a promising option, but the non-stable calorific value (CV) of PG from different biomasses poses a serious problem for the efficient operation of a dual-fuel engine. This study aims to examine how the CV of PG from various biomasses affects a 3.75-kW dual-fuel IC engine's performance. The experimental facility, which has a dual-fuel engine and a 115-kW thermal gasifier, tested the blends of diesel and PG from different biomasses. We chose biomass based on its availability and PG's CV of 3.4, 4.4, 5.2, and 6.3 MJ/Nm3. For this range of CV, the efficiency, energy consumption, and fuel replacement of a dual-fuel engine vary between 20.9 and 26.6%, 17.3 and 13.5 MJ/kWh, and 10.8 and 76.9%, respectively. Furthermore, the blend with the maximum CV of PG had a 69.64% lower specific diesel consumption and an 86% higher diesel replacement rate than the blend with the lowest CV of PG. In terms of emission characteristics, the comparison showed a 2.02-7.06% reduction in NOx and a 4.05-55.6% increase in hydrocarbons (HCs) for the tested conditions. The overall observations demonstrated that a significant enhancement in a dual-fuel engine's performance is possible with a higher CV of PG. However, the emissions trade-offs demand additional optimization studies, as well as case-based research, in order to integrate renewable energy and emission management in smaller-scale applications across more geographies.

Corrigendum: BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways.

[This corrects the article DOI: 10.3389/fphar.2023.1265230.].

Design, synthesis, molecular modeling, in vitro and in vivo biological evaluation of potent anthranilamide derivatives as dual P-glycoprotein and CYP3A4 inhibitors.

Paclitaxel (PTX) is considered the blockbuster chemotherapy treatment for cancer. Paclitaxel's (PTX) oral administration has proven to be extremely difficult, mostly because of its susceptibility to intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP3A4). The concurrent local inhibition of intestinal P-gp and CYP3A4 is a promising approach to improve the oral bioavailability of paclitaxel while avoiding potential unfavorable side effects of their systemic inhibition. Herein, we report the rational design and evaluation of novel dual potent inhibitors of P-gp and CYP3A4 using an anthranilamide derivative tariquidar as a starting point for their structural optimizations. Compound 14f, bearing N-imidazolylbenzyl side chain, was found to have potent and selective P-gp (EC50 = 28 nM) and CYP3A4 (IC50 = 223 nM) inhibitory activities with low absorption potential (Papp (A-to-B) <0.06). In vivo, inhibitor 14f improved the oral absorption of paclitaxel by 6 times in mice and by 30 times in rats as compared to vehicle, while 14f itself remained poorly absorbed. Compound 14f, possessing dual P-gp and CYP3A4 inhibitory activities, offered additional enhancement in paclitaxel oral absorption compared to tariquidar in mice. Evaluating the CYP effect of 14f on oral absorption of paclitaxel requires considering the variations in CYP expression between animal species. This study provides further medicinal chemistry advice on strategies for resolving concerns with the oral administration of chemotherapeutic agents.

Patterns and outcomes of acute toxicological cases before, during, and after COVID-19 lockdown in Sohag University hospitals, Egypt.

Background: Toxicologists manage poisoning by preventing, detecting, and treating it, which requires continuous data collection and analysis of toxicological hazards. Aim of the work: The study aims to report and compare the pattern and outcome of acute toxicological cases admitted to Sohag University Hospitals during the COVID-19 lockdown (2020-2021) with the year before (2019) and the year after (2022). Methods: This comparative study reviewed the sociodemographic and clinical data in the medical records. The study showed that Sohag University Hospitals received 670 toxicological cases between 2019 and 2022; 105 cases in 2019, 347 cases in 2020-2021, and 218 cases in 2022. Results: Most of patients were below seven years with no sex differences. Accidental poisoning was the most frequent toxicity. The oral route was the most common in the three studied periods. During the lockdown, metal phosphide was the most frequent (19.0%), while therapeutic agents were the most reported after the lockdown (23.9%). The delay time showed a significant difference between the studied periods (p-value < 0.001). In the three studied periods, complete recovery was achieved in more than 70% of cases; however, the mortality rate and the rate of complications during the lockdown period (10.4% and 9.5%, respectively) were almost twice those of the year before and the year after the pandemic with significant odds ratio of mortality during pandemic (OR) 0.07 CI 95% (0.02, 0.11). Conclusion: The pandemic had a bad impact on outcomes as showed the highest percentage of mortality compared to before and after COVID-19 periods.

An International Survey of Extracorporeal Membrane Oxygenation Education and Credentialing Practices.

Background: The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly over the past decades because of evolving indications, advances in circuit technology, and encouraging results from modern trials. Because ECMO is a complex and highly invasive therapy that requires a multidisciplinary team, optimal education, training, and credentialing remain a challenge. Objective: The primary objectives of this study were to investigate the prevalence and application of ECMO education and ECMO practitioner credentialing at ECMO centers globally. In addition, we explored differences among education and credentialing practices in relation to various ECMO center characteristics. Methods: We conducted an observational study of ECMO centers worldwide using a survey querying participants in two major domains: ECMO education and ECMO practitioner credentialing. Of note, the questionnaire included ECMO program characteristics, such as type and size of hospital and ECMO experience and volume, to explore the association with the two domains. Results: A total of 241 (32%) of the 732 identified ECMO centers responded to the survey, representing 41 countries across the globe. ECMO education was offered at 221 (92%) of the 241 centers. ECMO education was offered at 105 (98.0%) high-ECMO volume centers compared with 136 (87.5%) low-ECMO volume centers (P = 0.005). Credentialing was established at 101 (42%) of the 241 centers. Credentialing processes existed at 52 (49.5%) high-ECMO volume centers compared with 51 (37.5%) low-ECMO volume centers (P = 0.08) and 101 (49.3%) Extracorporeal Life Support Organization centers compared with 1 (2.7%) non-Extracorporeal Life Support Organization center (P < 0.001). Conclusion: We found significant variability in whether ECMO educational curricula are offered at ECMO centers. We also found fewer than half of the ECMO centers surveyed had established credentialing programs for ECMO practitioners. Future studies that assess variability in outcomes among centers with and without standardized educational and credentialing practices are needed.

Efficacy of laser biostimulation for mandibular narrow ridges treated with one-stage ridge splitting and two-implant overdentures: A one-year preliminary study.

STATEMENT OF PROBLEM: The management of patients with narrow-mandibular ridges who seek prosthetic rehabilitation is challenging. PURPOSE: The purpose of this one-year preliminary clinical study was to compare the effects of laser biostimulation and a placebo on peri-implant tissues for a 2-implant-retained mandibular polyetheretherketone (PEEK) overdenture on expanded narrow mandibular ridges. MATERIAL AND METHODS: Eighteen completely edentulous participants were enrolled for mandibular ridge splitting in the canine regions, followed by expansion, the placement of implants, and the application of a bone graft. In the test group, laser therapy was applied labially and lingually at the surgical sites, while a placebo laser was used in the control group. PEEK overdentures retained by LOCATOR attachments were provided after 6 months. Clinical evaluations were performed using probing depth, plaque, bleeding, and gingival indices at insertion and 3, 6, and 12 months after insertion. Vertical bone loss (VBL) was evaluated with periapical radiograph at insertion and 6 and 12 months later. The Mann-Whitney test was used to test the difference between the 2 different groups at each evaluation time (α=.05). The Friedman-test was used, followed by Wilcoxon signed rank test, to test the change over time in the same group, and the Bonferroni adjusted significance level was used for multiple comparisons. RESULTS: Some clinical and radiographic parameters significantly increased with time in both groups (P<.001). Significant differences between the 2 groups were revealed in bleeding scores at 3 months (P=.006) and 6 months (P=.018). Also, significant differences between the 2 groups were observed in gingival scores at 3 months (P=.002), 6 months (P=.015), and 12 months (P=.019) after overdenture insertion in favor of the laser group. Peri-implant VBL was significantly higher in the non-laser group at 6 months (P=.015), and 12 months (P=.001). CONCLUSIONS: Within the limitations of this clinical study, respecting the small sample size and the short follow-up period, laser bio-stimulation after 1-stage ridge splitting in narrow mandibular ridges enhanced the soft and hard peri implant tissues when used with LOCATOR attachments and PEEK overdentures.

Refugee health and physiological profiles in transitional settlements in Serbia and Kenya: Comparative evidence for effects of gender and social support.

When armed conflict compels people to flee from their homelands, they embark on protracted journeys during which they experience wide ranging physical, social, and psychological challenges. Few studies have focused on refugee psychosocial and physiological profiles during the transitional phase of forced migration that often involves temporary sheltering. Transient refugees' experiences can vary substantially based on local socio-ecological conditions in temporary settlements, including the length of stay, living conditions, as well as the availability and accessibility of physical and social resources. In this study, we compared physiological and psychosocial data from refugees (N=365; 406 observations) in Serbia and Kenya, respectively, with divergent temporal (length of stay) and socio-ecological conditions. In Serbia, refugees resided in asylum centers (mean stay: 0.9 y); in Kenya they were living in Kakuma Refugee Camp (mean stay: 8.8 y), one of the world's largest camps at the time. We had limited ability to directly compare psychosocial measures and used meta-analytic techniques to evaluate predictors of refugee mental and physical health at the two sites, including based on perceived social support. Refugees in Serbia had higher fingernail cortisol (p < 0.001) and were less likely to have elevated C-reactive protein (CRP) levels (p < 0.01) than refugees in Kakuma. We found common gender differences in both settings; women had lower cortisol but higher EBV antibody titers and higher likelihood of having elevated CRP compared to men (all p < 0.01). Woman also reported poorer mental and physical health (p < 0.001). These physiological and health differences may reflect variation between men and women in their psychosocial and physical experiences of factors such as stress, violence, and trauma during their journeys and as transitional refugees. Finally, we also found that refugees with lower levels of perceived social support reported poorer physical and mental health (p < 0.001). Although our results are cross-sectional, they suggest that this intermittent phase of the refugee experience is a key window for helping enhance refugee well-being through an emphasis on interpersonal and community support systems.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients.

Objectives Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC). Case series have described the use of methylnaltrexone for OIC in the pediatric oncology population. There are limited data describing its intravenous use in critically ill pediatric patients. Methods We conducted a retrospective observational study at St. Louis Children's Hospital. Patients less than 18 years old who received at least one dose of intravenous methylnaltrexone while admitted to an intensive care unit between January 2016 and August 2019 were included. The primary outcome was documented laxation within 24 hours of methylnaltrexone administration. Results Sixteen patients received a total of 34 doses of intravenous methylnaltrexone. Patients received a median of 1.69 (interquartile range [IQR], 0.9-4.86) morphine milligram equivalents per kilogram per 24 hours, over a median of 14 days (IQR, 11-30), before methylnaltrexone administration. The median dose of methylnaltrexone was 0.15 mg/kg (IQR, 0.15-0.16). Ten patients (63%) responded to the first dose of methylnaltrexone, and 14 patients (88%) responded to at least one dose. Overall, 26 doses (76%) led to patient response. Four patients (25%) experienced adverse events (emesis, abdominal pain) after methylnaltrexone administration. No signs or symptoms of opioid withdrawal were documented. Conclusions Intravenous methylnaltrexone appears to be safe and effective in treating OIC in critically ill pediatric patients. No serious adverse events or signs of opioid withdrawal were observed after single and repeat dosing. Patients responded to methylnaltrexone with varying opioid dosing and durations prior to administration.

Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development.

Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. MATERIALS AND METHODS: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0-18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. RESULTS: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. CONCLUSIONS: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.

In vivo measurement of pediatric extracorporeal oxygenator insensible losses; a single center pilot study.

Introduction: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous in vitro studies have attempted to quantify oxygenator-related insensible losses, as failure to account for this fluid loss may lead to inaccurate fluid balance assessment and potentially harmful clinical management, such as unnecessary exposure to diuretics, slow continuous ultrafiltration (SCUF), or continuous kidney replacement therapy (CKRT). We performed a novel in vivo study to measure insensible fluid losses in pediatric ECMO patients. Methods: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow. Results and discussion: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m2 IQR [0.315, 1.3725]. Overall, the cohort had a median sweep of 2.5 L/min [0.9, 4], ECMO flow of 3.975 L/m2/min [0.75, 4.51], and a set ECMO temperature of 37 degrees Celsius [36.6, 37.2]. The calculated net water loss per L/min of sweep was 75.93 ml/day, regardless of oxygenator size or patient weight. There was a significant difference in median documented vs. calculated fluid balance incorporating the insensible fluid loss, irrespective of oxygenator size (pediatric oxygenator: 7.001 ml/kg/day [-12.37, 28.59] vs. -6.11 ml/kg/day [-17.44, 13.01], respectively, p = 0.005 and adult oxygenator: 14.36 ml/kg/day [1.54, 25.77] and 9.204 ml/kg/day [-1.28, 22.05], respectively, p = <0.001). We present this pilot study of measured oxygenator-associated insensible fluid losses on ECMO. Our results are consistent with prior in vitro methods and provide the basis for future studies evaluating the impact of incorporating these fluid losses into patients' daily fluid balance on patient management and outcomes.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

BACKGROUND: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). METHODS: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. RESULTS: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. CONCLUSIONS: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Double-side 2D/3D heterojunctions for inverted perovskite solar cells.

Defects at the top and bottom interfaces of three-dimensional (3D) perovskite photoabsorbers diminish the performance and operational stability of perovskite solar cells owing to charge recombination, ion migration and electric-field inhomogeneities1-5. Here we demonstrate that long alkyl amine ligands can generate near-phase-pure 2D perovskites at the top and bottom 3D perovskite interfaces and effectively resolve these issues. At the rear-contact side, we find that the alkyl amine ligand strengthens the interactions with the substrate through acid-base reactions with the phosphonic acid group from the organic hole-transporting self-assembled monolayer molecule, thus regulating the 2D perovskite formation. With this, inverted perovskite solar cells with double-side 2D/3D heterojunctions achieved a power conversion efficiency of 25.6% (certified 25.0%), retaining 95% of their initial power conversion efficiency after 1,000 h of 1-sun illumination at 85 °C in air.

Interactive Narrative-Based Digital Health Interventions for Vaccine Communication: Protocol for a Scoping Review.

BACKGROUND: Interactive narrative-based digital health interventions hold promise for effectively addressing the complex determinants of vaccine hesitancy and promoting effective communication across a wide range of settings and vaccine types. Synthesizing evidence related to the implementation and evaluation of these interventions could offer valuable perspectives for shaping future strategies in vaccine communication. Prior systematic and scoping reviews have examined narrative-based vaccine communication interventions but not the inclusion of interactivity in such interventions. OBJECTIVE: The overall objective of the scoping review is to summarize the evidence on the use of interactive narrative-based digital health interventions for vaccine communication. Specific research questions focus on describing the use of interactive narrative-based digital health interventions (RQ1), describing evaluations of the impact of interactive narrative-based digital health interventions on promoting vaccine uptake (RQ2), and factors associated with their implementation (RQ3). METHODS: A detailed search string will be used to search the following databases for records that are relevant to the review questions: PubMed, Embase, Scopus, Web of Science, CINAHL, and PsycINFO. Two reviewers will independently screen the titles and abstracts of identified records against the predefined eligibility criteria. Subsequently, eligible records will undergo comprehensive full-text screening by 2 independent reviewers to assess their relevance to review questions. A data charting tool will be developed and used to extract relevant information from the included articles. The extracted information will be analyzed following the review questions and presented as a narrative summary. Tabular or graphical representations will be used to display review findings, as relevant. RESULTS: Public health informationists were consulted to develop the detailed search strategy. The final search string comprised terms related to narrative communication, digital health, and vaccines. The search string was customized to each proposed publication database and implemented on April 18, 2023. A total of 4474 unique records were identified using the search strategy and imported into the Covidence (Veritas Health Innovation Ltd) review management software for title and abstract screening. Title and abstract screening of identified records are ongoing as of December 29, 2023. CONCLUSIONS: To our knowledge, this will be the first scoping review to investigate the features of interactive narrative-based digital health interventions and their role in vaccine communication. The goal of this study is to provide a comprehensive overview of the current research landscape and identify prevailing gaps in knowledge. The findings will provide insights for future research and development of novel applications of interactive narrative-based digital health vaccine communication interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51137.

Single Ventricular Assist Device Care and Outcomes for Failed Stage I Palliation: A Single-Center Decade of Experience.

Single ventricular assist device (SVAD) use before and after stage I palliation (S1P) is increasing with limited data on outcomes. To address this knowledge gap, we conducted a single-center retrospective review to assess pre- and post-SVAD clinical status, complications, and outcomes. We leveraged a granular, longitudinal, local database that captures end-organ support, procedural interventions, hematologic events, laboratory data, and antithrombotic strategy. We identified 25 patients between 2013 and 2023 implanted at median age of 53 days (interquartile range [IQR] = 16-130); 80% had systemic right ventricles and underwent S1P. Median SVAD days were 54 (IQR = 29-86), and 40% were implanted directly from ECMO. Compared to preimplant, there was a significant reduction in inotrope use ( p = 0.013) and improved weight gain ( p = 0.008) post-SVAD. Complications were frequent including bleeding (80%), stroke (40%), acute kidney injury (AKI) (40%), infection (36%), and unanticipated catheterization (56%). Patients with in-hospital mortality had significantly more bleeding complications ( p = 0.02) and were more likely to have had Blalock-Thomas-Taussig shunts pre-SVAD ( p = 0.028). Survival to 1 year postexplant was 40% and included three recovered and explanted patients. At 1 year posttransplant, all survivors have technology dependence or neurologic injury. This study highlights the clinical outcomes and ongoing support required for successful SVAD use in failed single-ventricle physiology before or after S1P.

Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers.

Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 µM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.

Long-Term Neurobehavioral and Functional Outcomes of Pediatric Extracorporeal Membrane Oxygenation Survivors.

There are limited reports of neurobehavioral outcomes of children supported on extracorporeal membrane oxygenation (ECMO). This observational study aims to characterize the long-term (≥1 year) neurobehavioral outcomes, identify risk factors associated with neurobehavioral impairment, and evaluate the trajectory of functional status in pediatric ECMO survivors. Pediatric ECMO survivors ≥1-year postdecannulation and ≥3 years of age at follow-up were prospectively enrolled and completed assessments of adaptive behavior (Vineland Adaptive Behavior Scales, Third Edition [Vineland-3]) and functional status (Functional Status Scale [FSS]). Patient characteristics were retrospectively collected. Forty-one ECMO survivors cannulated at 0.0-19.8 years (median: 2.4 [IQR: 0.0, 13.1]) were enrolled at 1.3-12.8 years (median: 5.5 [IQR: 3.3, 6.5]) postdecannulation. ECMO survivors scored significantly lower than the normative population in the Vineland-3 Adaptive Behavior Composite (85 [IQR: 70, 99], P < 0.001) and all domains (Communication, Daily Living, Socialization, Motor). Independent risk factors for lower Vineland-3 composite scores included extracorporeal cardiopulmonary resuscitation, electrographic seizures during ECMO, congenital heart disease, and premorbid developmental delay. Of the 21 patients with impaired function at discharge (FSS ≥8), 86% reported an improved FSS at follow-up. Pediatric ECMO survivors have, on average, mild neurobehavioral impairment related to adaptive functioning years after decannulation. Continued functional recovery after hospital discharge is likely.