Translational Research Research Articles

Emerging Nanotechnology in Preclinical Pancreatic Cancer Immunotherapy: Driving Towards Clinical Applications.

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.

ECR Spotlight – Sara Wilmsen

ECR Spotlight is a series of interviews with early-career authors from a selection of papers published in Journal of Experimental Biology and aims to promote not only the diversity of early-career researchers (ECRs) working in experimental biology but also the huge variety of animals and physiological systems that are essential for the ‘comparative’ approach. Sara Wilmsen is an author on ‘ Chronic changes in developmental oxygen have little effect on mitochondria and tracheal density in the endothermic moth Manduca sexta’, published in JEB. Sara is a Research Scientist in the lab of Dr Micheal Purdy at Snyder Translational Research, USA, investigating the unique respiratory systems of invertebrates; specifically, insects and spiders.

Tenebrio molitor as a new alternative model for the investigation of chemotherapy-induced intestinal toxicity

Alternative animal models have become increasingly necessary due to legal regulations aimed at reducing the use of laboratory animals. Invertebrates are gaining in importance and have been intensively researched in recent years due to their pathophysiological similarities with rodents. Among these organisms, Tenebrio molitor, also known as the yellow mealworm beetle, stands out. In this study, we investigated whether T. molitor could be an alternative for studying the toxicity of chemotherapeutic agents. For this purpose, T. molitor larvae were inoculated with irinotecan (IRI) or 5-fluorouracil (5-FU). Both chemotherapeutic agents increased the morbidity and mortality of T. molitor and led to an increase in total circulating cells. Glucose levels were decreased after treatment with 5-FU and alanine aminotransferase levels were decreased after IRI administration. Administration of IRI or 5-FU resulted in changes in the appearance, consistency and amount of T. molitor frass. Finally, both IRI and 5-FU promoted severe histologic damage in the midgut and increased melanin deposition in peripheral tissues. Finally, we succeeded in developing an alternative experimental model for evaluating the toxicity of IRI and 5-FU. This model exhibits significant features of toxicity and intestinal damage, making it suitable for translational research purposes. T. molitor proves to be a versatile model organism with numerous advantages for experimental studies and offers a viable alternative for acquiring and expanding knowledge in the field of toxicology and pharmacology.

Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL)-A Scoping Review Based on Preclinical Studies.

Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) stabilizes the corneal stroma and eliminates microorganisms. Numerous PACK-CXL protocols, using different energy sources and chromophores, have been applied in preclinical studies, including live animal studies, with various experimental designs and endpoints. So far, a systematic mapping of the applied protocols and consistency across studies seems lacking but is essential to guide future research. The scoping review protocol was in line with the JBI Manual for Evidence Synthesis. Electronic databases were searched (Embase, MEDLINE, Scopus, Web of Science) to identify eligible records, followed by a two-step selection process (title and abstract screening, full text screening) for record inclusion. We extracted information on (1) different PACK-CXL protocol characteristics; (2) infectious pathogens tested; (3) study designs and experimental settings; and (4) endpoints used to determine antimicrobial and tissue stabilizing effects. The information was charted in frequency maps. The searches yielded 3654 unique records, 233 of which met the inclusion criteria. With 103 heterogeneous endpoints, the researchers investigated a wide range of PACK-CXL protocols. The tested microorganisms reflected pathogens commonly associated with infectious keratitis. Bacterial solutions and infectious keratitis rabbit models were the most widely used models to study the antimicrobial effects of PACK-CXL. If preclinical PACK-CXL studies are to guide future translational research, further cross-disciplinary efforts are needed to establish, promote, and facilitate acceptance of common endpoints relevant to PACK-CXL. Systematic mapping of PACK-CXL protocols in preclinical studies guides future translational research.

Whole Blood Aggregometry in Mice.

Aggregometry plays a crucial role in both clinical diagnostics and research within hematology, serving as a fundamental tool for understanding platelet function and its implications in physiological and pathological processes. In research, aggregometry provides insights into platelet aggregation dynamics and aids in understanding the underlying mechanisms of hemostasis, thrombosis, and related disorders. Light transmission aggregometry (LTA) and lumi-aggregometry, as well as whole blood aggregometry, are commonly employed methods. While LTA and lumi-aggregometry allow for specific platelet function assessment under controlled conditions, whole blood aggregometry provides a more physiologically relevant approach by evaluating platelet aggregation within the context of whole blood. Although both methodologies offer unique advantages, whole blood aggregometry allows for preservation of the native cellular environment, simplicity, and potential for better clinical correlation. In a clinical setting, with human blood samples, protocols are established for both LTA and whole blood aggregometry as they are frequently used diagnostic tools. A protocol for LTA and lumi-aggregometry in murine models has been described; however, to date, there is no standardized protocol for whole blood aggregometry in murine models accessible to hematology researchers. This article aims to outline a simple, basic protocol for murine whole blood aggregometry, offering an alternative method to the commonly used LTA aggregometry in research settings. Standardizing whole blood aggregometry protocols in murine models could enhance experimental reliability and facilitate translational research efforts in hematology. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Whole blood aggregometry in mice Support Protocol: Phenylhydrazine-induced anemia in wild-type mice Basic Protocol 2: Hematocrit percentage in mice.

Comprehensive Flow Cytometric, Immunohistologic, and Molecular Assessment of Thymus Function in Rhesus Macaques.

The critical importance of the thymus for generating new naive T cells that protect against novel infections and are tolerant to self-antigens has led to a recent revival of interest in monitoring thymic function in species other than humans and mice. Nonhuman primates such as rhesus macaques (Macaca mulatta) provide particularly useful animal models for translational research in immunology. In this study, we tested the performance of a 15-marker multicolor Ab panel for flow cytometric phenotyping of lymphocyte subsets directly from rhesus whole blood, with validation by thymectomy and T cell depletion. Immunohistochemical and multiplex RNA expression analysis of thymus tissue biopsies and molecular assays on PBMCs were used to further validate thymus function. Results identify Ab panels that can accurately classify rhesus naive T cells (CD3+CD45RA+CD197+ or CD3+CD28+CD95-) and recent thymic emigrants (CD8+CD28+CD95-CD103+CD197+) using just 100 µl of whole blood and commercially available fluorescent Abs. An immunohistochemical panel reactive with pan-cytokeratin (CK), CK14, CD3, Ki-67, CCL21, and TdT provides histologic evidence of thymopoiesis from formalin-fixed, paraffin-embedded thymus tissues. Identification of mRNAs characteristic of both functioning thymic epithelial cells and developing thymocytes and/or molecular detection of products of TCR gene rearrangement provide additional complementary methods to evaluate thymopoiesis, without requiring specific Abs. Combinations of multiparameter flow cytometry, immunohistochemistry, multiplex gene expression, and TCR excision circle assays can comprehensively evaluate thymus function in rhesus macaques while requiring only minimal amounts of peripheral blood or biopsied thymus tissue.

Epigenetics in thyroid cancer: a bibliometric analysis.

Epigenetics, which involves regulatory modifications that do not alter the DNA sequence itself, is crucial in the development and progression of thyroid cancer. This study aims to provide a comprehensive analysis of the epigenetic research landscape in thyroid cancer, highlighting current trends, major research areas, and potential future directions. A bibliometric analysis was performed using data from the Web of Science Core Collection (WOSCC) up to November 1, 2023. Analytical tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed for comprehensive data analysis and visualization. This process identified principal research themes, along with influential authors, institutions, and countries contributing to the field. The analysis reveals a marked increase in thyroid cancer epigenetics research over the past two decades. Emergent key themes include the exploration of molecular mechanisms and biomarkers, various subtypes of thyroid cancer, implications for therapeutic interventions, advancements in technologies and methodologies, and the scope of translational research. Research hotspots within these themes highlight intensive areas of study and the potential for significant breakthroughs. This study presents an in-depth overview of the current state of epigenetics in thyroid cancer research. It underscores the potential of epigenetic strategies as viable therapeutic options and provides valuable insights for researchers and clinicians in advancing the understanding and treatment of this complex disease. Future research is vital to fully leverage the therapeutic possibilities offered by epigenetics in the management of thyroid cancer.

High ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia: an observational study

High ambient temperature is increasingly common due to climate change and is associated with risk of adverse pregnancy outcomes. Acute lymphoblastic leukaemia is the most common malignancy in children, the incidence is increasing, and in the USA disproportionately affects Latino children. We aimed to investigate the potential association between high ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia. We used data from California birth records (children born from Jan 1, 1982, to Dec 31, 2015) and California Cancer Registry (those diagnosed with childhood cancer in California from Jan 1, 1988, to Dec 31, 2015) to identify acute lymphoblastic leukaemia cases diagnosed in infants and children aged 14 years and younger and controls matched by sex, race, ethnicity, and date of last menstrual period. Ambient temperatures were estimated on a 1-km grid. The association between ambient temperature and acute lymphoblastic leukaemia was evaluated per gestational week, restricted to May-September, adjusting for confounders. Bayesian meta-regression was applied to identify critical exposure windows. For sensitivity analyses, we evaluated a 90-day pre-pregnancy period (assuming no direct effect before pregnancy), adjusted for relative humidity and particulate matter less than 2·5 microns in aerodynamic diameter, and constructed an alternatively matched dataset for exposure contrast by seasonality. 6849 cases of childhood acute lymphoblastic leukaemia were identified and, of these, 6258 had sufficient data for study inclusion. We also included 307 579 matched controls. Most of the study population were male (174 693 [55·7%] of the 313 837 included in the study) and of Latino ethnicity (174 906 [55·7%]). The peak association between ambient temperature and risk of acute lymphoblastic leukaemia was observed in gestational week 8, where a 5°C increase was associated with an odds ratio of 1·07 (95% CI 1·04-1·11). A slightly larger effect was seen among Latino children (OR 1·09 [95% CI 1·04-1·14]) than non-Latino White children (OR 1·05 [1·00-1·11]). The sensitivity analyses supported the results of the main analysis. Our findings suggest an association between high ambient temperature in early pregnancy and risk of childhood acute lymphoblastic leukaemia. Further replication and investigation of mechanistic pathways might inform mitigation strategies. Yale Center on Climate Change and Health, The National Center for Advancing Translational Science, National Institutes of Health.

HDAC6 inhibition as a mechanism to prevent neurodegeneration in the mSOD1G93A mouse model of ALS.

The loss of upper and lower motor neurons, and their axons is central to the loss of motor function and death in amyotrophic lateral sclerosis (ALS). Due to the diverse range of genetic and environmental factors that contribute to the pathogenesis of ALS, there have been difficulties in developing effective therapies for ALS. One emerging dichotomy is that protection of the neuronal cell soma does not prevent axonal vulnerability and degeneration, suggesting the need for targeted therapeutics to prevent axon degeneration. Post-translational modifications of protein acetylation can alter the function, stability and half-life of individual proteins, and can be enzymatically modified by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), which add, or remove acetyl groups, respectively. Maintenance of post-translational microtubule acetylation has been suggested as a mechanism to stabilise axons, prevent axonal loss and neurodegeneration in ALS. This study used an orally dosed potent HDAC6 inhibitor, ACY-738, prevent deacetylation and stabilize microtubules in the mSOD1G93A mouse model of ALS. Co-treatment with riluzole was performed to determine any effects or drug interactions and potentially enhance preclinical research translation. This study shows ACY-738 treatment increased acetylation of microtubules in the spinal cord of mSOD1G93A mice, reduced lower motor neuron degeneration in female mice, ameliorated reduction in peripheral nerve axon puncta size, but did not prevent overt motor function decline. The current study also shows peripheral nerve axon puncta size to be partially restored after treatment with riluzole and highlights the importance of co-treatment to measure the potential effects of therapeutics in ALS.

Ensuring best practice in genomics education: A theory- and empirically informed evaluation framework.

Implementation of genomic medicine into healthcare requires a workforce educated through effective educational approaches. However, ascertaining the impact of genomics education activities or resources is limited by a lack of evaluation and inconsistent descriptions in the literature. We aim to support those developing genomics education to consider how best to capture evaluation data that demonstrate program outcomes and effectiveness within scope. Here, we present an evaluation framework that is adaptable to multiple settings for use by genomics educators with or without education or evaluation backgrounds. The framework was developed as part of a broader program supporting genomic research translation coordinated by the Australian Genomics consortium. We detail our mixed-methods approach involving an expert workshop, literature review and iterative expert input to reach consensus and synthesis of a new evaluation framework for genomics education. The resulting theory-informed and evidence-based framework encompasses evaluation across all stages of education program development, implementation and reporting, and acknowledges the critical role of stakeholders and the effects of external influences.

Unveiling Translation's Role in Soft Power: The Case of the TEDA Project

Literary translation has been one of the most intriguing fields of study in terms of translation studies. Like other forms of translation, it encompasses not only linguistic transfer but also cultural transfer. Considering that cultural elements and literary features are prominent in literary texts, it is no surprise that literary translation gained significant ground in translation research. Despite the challenges faced in the process of literary translation, its contributions to literature, readers, and intercultural understanding outweigh. Apart from these, translation's role in fostering a country's soft power should not be underestimated. As a resource reflecting a nation's culture with abundant cultural elements, literary translation is one of the most substantial domains of translation that can have a pivotal role in soft power. In parallel with all these contributions of translation, the promotion of literature through translation on a global scale comes into prominence. Promoting literature belonging to less prevalent languages is even more crucial as the authors of such literature need to show more effort to make their voices heard in broader geographies. To fulfill this goal, translation projects that provide such an opportunity for authors play a significant role. From this point of view, this study aims to present a clear framework of literary works translated from Turkish literature into Spanish language within the scope of TEDA project funded by the Turkish Ministry of Culture and Tourism. The literary works translated into Spanish are presented based on elements such as the authors, translators, publishing houses, literary genres, countries, years, and titles of the books in the source language and target language. The results reveal that there is a remarkable amount of effort to make Turkish literature recognized in Spanish-speaking regions; however, there is still a long way to go as the number of translations and diversification in terms of authors, translators, and literary genres are still limited and translations of the book titles sometimes could not avoid stereotypes about Turkish culture.

Addressing Burnout and Enhancing Well-Being Among Academic Physicians: A Call for Future Research and Organizational Support.

Description Burnout among academic physicians, who navigate multiple roles beyond the clinical environment, is a pressing issue. However, the factors driving burnout among academic physicians are not fully understood. Prior research has revealed differences in burnout dimensions between clinical and basic science faculty, but the impact of balancing research, education, and clinical demands on academic physicians is still unclear. This knowledge gap negatively affects the clinical, translational science, research, and medical education workforces and has particular implications for minoritized and marginalized groups working in academic medical centers. Creating a culture of well-being has been vital in addressing burnout. Further research is needed to explore the unique experiences and demands of academic physicians- particularly those from minoritized and marginalized backgrounds-and to develop effective strategies to promote well-being as they balance diverse roles and contexts. This commentary highlights gaps in understanding burnout among academic physicians and proposes guidelines for future research as well as strategies to improve well-being at academic medical centers.

Verbatim theatre as a creative approach to health professions education research translation.

Traditionally, the impact and outcomes from health professions education research (HPER) have focused on academic outputs, whereas in the humanities, research translation is conceptualised more broadly and creatively, including research-based performances like verbatim theatre. Translating HPER findings through the emotive and embodied nature of a verbatim theatre performance provides a unique opportunity to translate research data and create alternative learning spaces for rich and valuable insights that aligns with transformative pedagogy. In this paper, we describe the background of verbatim theatre, a form of performance, which draws on a research participants' testimony and lived experience and how we used this creative approach to translate HPER findings. We discuss the experiential process of bringing an interdisciplinary team together, health professions academics and an academic playwright to craft a verbatim theatre script that provided space to honour the breadth, depth and diversity of participant voices from a large (n = 100) qualitative research study exploring professionalism and sociocultural factors in health professions education (HPE). Furthermore, we discuss the powerful potential of drawing on research-based performance to create alternative, safe and non-threatening learning spaces to resonate with and experience HPER in new and transformative ways. Finally, we offer reflexive insights on the key opportunities and challenges we encountered in translating HPER into a verbatim theatre performance. Verbatim theatre presents an innovative and creative way to communicate and translate HPER. This paper offers research and pedagogical insights in translating research into verbatim theatre to support transformative pedagogy and practice in HPE. In conclusion, we encourage other health professions researchers to consider this dynamic and creative approach to transforming HPE.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing (ES), the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare disease. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery which should in turn increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints, and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks like Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.

(Semi)automated approaches to data extraction for systematic reviews and meta-analyses in social sciences: A living review

Background An abundance of rapidly accumulating scientific evidence presents novel opportunities for researchers and practitioners alike, yet such advantages are often overshadowed by resource demands associated with finding and aggregating a continually expanding body of scientific information. Data extraction activities associated with evidence synthesis have been described as time-consuming to the point of critically limiting the usefulness of research. Across social science disciplines, the use of automation technologies for timely and accurate knowledge synthesis can enhance research translation value, better inform key policy development, and expand the current understanding of human interactions, organizations, and systems. Ongoing developments surrounding automation are highly concentrated in research for evidence-based medicine with limited evidence surrounding tools and techniques applied outside of the clinical research community. The goal of the present study is to extend the automation knowledge base by synthesizing current trends in the application of extraction technologies of key data elements of interest for social scientists. Methods We report the baseline results of a living systematic review of automated data extraction techniques supporting systematic reviews and meta-analyses in the social sciences. This review follows PRISMA standards for reporting systematic reviews. Results The baseline review of social science research yielded 23 relevant studies. Conclusions When considering the process of automating systematic review and meta-analysis information extraction, social science research falls short as compared to clinical research that focuses on automatic processing of information related to the PICO framework. With a few exceptions, most tools were either in the infancy stage and not accessible to applied researchers, were domain specific, or required substantial manual coding of articles before automation could occur. Additionally, few solutions considered extraction of data from tables which is where key data elements reside that social and behavioral scientists analyze.

Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration.

Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.

Hemodynamics in Coronary Arteries: using Open-Source Software-Simvascular to Investigate the Hemodynamics in Coronary Arteries of the Patient-Specific Modeling

Patient-specific cardiovascular simulation is emerging as a potent tool for basic, translational, and clinical research and has established itself as a paradigm in the field of cardiovascular science. The SimVascular software package, considered a state-of-the-art open-source package, offers a comprehensive pipeline from medical imaging data segmentation to patient-specific blood flow simulation and analysis. In this study, we employ SimVascular to explore a model of coronary arteries in a young and healthy 24-year-old woman. The outcomes of the entire simulation process encompass the assessment of flow and pressure waveforms at both the outlet of the aorta and the coronary arteries, which serve as indicators of blood flow qualities within these vessels. Given the pivotal role of wall shear stress in the development of arterial plaque, SimVascular employs the finite element method to solve the governing equations of incompressible viscous fluids. This approach effectively tackles the Navier-Stokes equations along the vessel wall using meticulously constructed mesh components. Additionally, this paper delves into the issue of cardiovascular blood vessel dynamics via an analysis of wall shear stress data).

HGG-46. PEDIATRIC RADIATION-INDUCED GLIOMA PATIENT SAMPLES AND NOVEL PATIENT-DERIVED MODELS REVEAL TRANSLATIONALLY RELEVANT TREATMENT SUSCEPTIBILITIES AND POTENTIAL GERMLINE RISK FACTORS

Abstract BACKGROUND Pediatric radiation-induced glioma (RIG) is an incurable secondary high-grade glioma (HGG) afflicting up to 4% of children who previously received cranial radiotherapy (RT) for other malignancies. RIG accounts for up to 10% of pediatric brain tumor deaths. It has no known genetic risk factors nor effective treatment and is uniformly fatal, partly due to extremely limited available models. Our recent molecular characterization of patient samples showed that while RIG and primary pediatric HGG share histological similarities, their genetic alterations and gene expression profiles differ. METHODS We obtained germline DNA sequencing from 28 RIG patients and 112 matched controls who received RT but did not develop RIG. In addition, we developed cell culture and murine orthotopic patient-derived xenograft (PDX) models from four RIGs. We conducted single-cell RNA-seq (scRNA-seq), drug screening/validation, and CRISPR functional screening on our novel models. RESULTS Germline mutations in TP53, PARP10, POLI, DCLRE1A, and MLH3 were more common in RIG patients than controls (p<0.002). Our matched cell culture and PDX models of RIG represent the genetic diversity of the disease. The PDX models form tumors in 30-120 days and closely recapitulate human RIG by histology and scRNA-seq. They show susceptibility across models to DNA-damaging treatments (etoposide, irinotecan, radiation), as well as MEK, PARP, and proteasome inhibition, with orthogonal supporting findings via CRISPR screening. Several two-treatment combinations also show efficacy and synergy across models, including radiation and trametinib in vivo (logrank p=0.029). Discussion: RIG is an understudied but major cause of pediatric CNS tumor mortality that differs genetically from primary pediatric HGG. Our findings suggest specific germline alterations in DNA repair pathways may put some patients at higher risk of developing RIG after cranial RT. We also introduce the first set of patient-derived RIG models in order to advance translational RIG research, with characterization of translationally relevant treatment susceptibilities.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

A streamlined approach to classifying and tailoring implementation strategies: recommendations to speed the translation of research to practice

BackgroundImplementation science emerged from the recognized need to speed the translation of effective interventions into practice. In the US, the science has evolved to place an ever-increasing focus on implementation strategies. The long list of implementation strategies, terminology used to name strategies, and time required to tailor strategies all may contribute to delays in translating evidence-based interventions (EBIs) into practice. To speed EBI translation, we propose a streamlined approach to classifying and tailoring implementation strategies.Main textA multidisciplinary team of eight scholars conducted an exercise to sort the Expert Recommendations for Implementing Change (ERIC) strategies into three classes: implementation processes (n = 25), capacity-building strategies (n = 20), and integration strategies (n = 28). Implementation processes comprise best practices that apply across EBIs and throughout the phases of implementation from exploration through sustainment (e.g., conduct local needs assessment). Capacity-building strategies target either general or EBI-specific knowledge and skills (e.g., conduct educational meetings). Integration strategies include “methods and techniques” that target barriers or facilitators to implementation of a specific EBI beyond those targeted by capacity building. Building on these three classes, the team collaboratively developed recommendations for a pragmatic, five-step approach that begins with the implementation processes and capacity-building strategies practice-settings are already using prior to tailoring integration strategies. A case study is provided to illustrate use of the five-step approach to tailor the strategies needed to implement a transitional care intervention in skilled nursing facilities.ConclusionsOur proposed approach streamlines the formative work required prior to implementing an EBI by building on practice partner preferences, expertise, and infrastructure while also making the most of prior research findings.