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Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

Over the past 3 decades, a substantial number of studies were published with the purpose of improving the effectiveness and efficiency of rehabilitation clinical practice. Clinicians and researchers face considerable challenges in successfully implementing these research findings into routine clinical practice. Knowledge translation includes the synthesis, dissemination, exchange, and ethically sound application of knowledge to improve health, provide more effective health services and products, and strengthen the health care system. An aim of knowledge translation research is to identify strategies to accelerate implementation of evidence into practice. A recent citation analysis on a commonly used knowledge translation framework, the Knowledge-to-Action Framework, identified implementation activities performed in physical medicine and rehabilitation. Although this citation analysis describes activities performed and outcomes assessed while conducting knowledge translation projects, successful knowledge translation also requires a robust social and physical infrastructure. In this commentary, we offer several observations that appear related to the increased likelihood of implementation success. Funders, higher education institutions, health care payers, and health care organizations contribute to successful implementation and must embrace their roles in implementation. Administrators, clinicians, and consumers of physical medicine and rehabilitation also have essential roles in knowledge translation. [ABSTRACT FROM AUTHOR]

Inflammation plays a critical role in conditions such as acute liver failure, acute-on-chronic liver failure, and ischemia-reperfusion-induced liver injury. Various pathogenic pathways contribute to liver inflammation, involving inflammatory polarization of macrophages and Küpffer cells, neutrophil infiltration, dysregulation of T cell subsets, oxidative stress, and activation of hepatic stellate cells. While mesenchymal stromal cells (MSCs) have demonstrated beneficial properties, their clinical translation is limited by their cellular nature. However, MSC-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach for immunomodulation. MSC-EVs naturally mirror their parental cell properties, overcoming the limitations associated with the use of MSCs. In vitro and in vivo preclinical studies have demonstrated that MSC-EVs replicate the beneficial effects of MSCs in liver injury. This includes the reduction of cell death and oxidative stress, improvement of hepatocyte function, induction of immunomodulatory effects, and mitigation of cytokine storm. Nevertheless, MSC-EVs face challenges regarding the necessity of defining consistent isolation methods, optimizing MSCs culture conditions, and establishing quality control measures for EV characterization and functional assessment. By establishing standardized protocols, guidelines, and affordable cost mass production, clinicians and researchers will have a solid foundation to conduct further studies, validate the therapeutic efficacy of MSC-EVs, and ultimately pave the way for their clinical implementation in acute liver injury., (© 2024. The Author(s).)

Metabolomic epidemiology studies are complex and require a broad array of domain expertise. Although many metabolite-phenotype associations have been identified; to date, few findings have been translated to the clinic. Bridging this gap requires understanding of both the underlying biology of these associations and their potential clinical implications, necessitating an interdisciplinary team approach. To address this need in metabolomic epidemiology, a workshop was held at Metabolomics 2023 in Niagara Falls, Ontario, Canada that highlighted the domain expertise needed to effectively conduct these studies -- biochemistry, clinical science, epidemiology, and assay development for biomarker validation -- and emphasized the role of interdisciplinary teams to move findings towards clinical translation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.)

The human genome encodes at least 500 protein kinases, and among them, there are at least 90 tyrosine kinases [...].

Background and Objective: Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel therapeutic targets. However, a lack of infrastructure for sample procurement, processing, storage, and shipping may hinder the ability of clinical research units to effectively engage in translational research. The purpose of this study was to identify the barriers to biosampling-based translational research in the critical care setting in Canada., Methods: We administered an online survey to members of the Canadian Critical Care Trials Group (CCCTG), the Canadian Critical Care Translational Biology Group (CCCTBG), and the Canadian Critical Care Research Coordinators Group (CCCRCG). The survey focused on participants' personal experience of biosampling research, research infrastructure, motivating factors, and perceived barriers., Results: We received 59 responses from 31 sites, including 6 community intensive care unit (ICU) sites. The overall response rate was 11.3%. The majority of respondents were research coordinators (44%), followed by clinician-investigators (33.8%), graduate students (10.2%), and PhD-investigators (8.5%). Although most (63.8%) respondents reported an interest in participating in translational research, they also reported that their ICUs were currently contributing to a third of the number of translational studies compared to clinical studies. For respondents with experience in participating in translational research studies, the most common barriers were lack of funding, lack of time, and insufficient research staff. For respondents without previous experience, the perceived facilitators were more interest from their research group, improved training/mentorship, increased funding, and better access to laboratory equipment., Conclusions: Our survey found that the majority of participants were interested in and recognize the value of participating in biosampling-based translational research but lacked funding, time, and research personnel trained in biosampling protocols. Our survey also identified factors that might encourage participation at new sites. Addressing these barriers will be a key step towards increasing translational research capacity across Canada., Competing Interests: No authors have competing interests., (Copyright: © 2024 Cani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microglia are the resident macrophages in the central nervous system, accounting for 10-15% of the cell mass in the brain. Next to their physiological role in development, monitoring neuronal function and the maintenance of homeostasis, microglia are crucial in the brain's immune defense. Brain injury and chronic neurological disorders are associated with neuroinflammation, in which microglia activation is a central element. Microglia acquire a wide spectrum of activation states in the diseased or injured brain, some of which are neurotoxic. The investigation of microglia (patho)physiology and therapeutic interventions targeting neuroinflammation is a substantial challenge. In addition to in vivo approaches, the application of in vitro model systems has gained significant ground and is essential to complement in vivo work. Primary microglia cultures have proved to be a useful tool. Microglia cultures have offered the opportunity to explore the mechanistic, molecular elements of microglia activation, the microglia secretome, and the efficacy of therapeutic treatments against neuroinflammation. As all model systems, primary microglia cultures have distinct strengths and limitations to be weighed when experiments are designed and when data are interpreted. Here, we set out to provide a succinct overview of the advantages and pitfalls of the use of microglia cultures, which instructs the refinement and further development of this technique to remain useful in the toolbox of microglia researchers. Since there is no conclusive therapy to combat neurotoxicity linked to neuroinflammation in acute brain injury or neurodegenerative disorders, these research tools remain essential to explore therapeutic opportunities., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical scope of gene therapies expands, consideration must be given to those who will benefit and what proactive steps must be taken to widen development and access potential, particularly in regions carrying a high disease burden.

Introduction: Patient engagement and integrated knowledge translation (iKT) processes improve health outcomes and care experiences through meaningful partnerships in consensus-building initiatives and research. Consensus-building is essential for engaging a diverse group of experienced knowledge users in co-developing and supporting a solution where none readily exists or is less optimal. Patients and caregivers provide invaluable insights for building consensus in decision-making around healthcare, policy and research. However, despite emerging evidence, patient engagement remains sparse within consensus-building initiatives. Specifically, our research has identified a lack of opportunity for youth living with chronic health conditions and their caregivers to participate in developing consensus on indicators/benchmarks for transition into adult care. To bridge this gap and inform our consensus-building approach with youth/caregivers, this scoping review will synthesise the extent of the literature on patient and other knowledge user engagement in consensus-building healthcare initiatives., Methods and Analysis: Following the scoping review methodology from Joanna Briggs Institute, published literature will be searched in MEDLINE, EMBASE, CINAHL and PsycINFO databases from inception to July 2023. Grey literature will be hand-searched. Two independent reviewers will determine the eligibility of articles in a two-stage process, with disagreements resolved by a third reviewer. Included studies must be consensus-building studies within the healthcare context that involve patient engagement strategies. Data from eligible studies will be extracted and charted on a standardised form. Abstracted data will be analysed quantitatively and descriptively, according to specific consensus methodologies, and patient engagement models and/or strategies., Ethics and Dissemination: Ethics approval is not required for this scoping review protocol. The review process and findings will be shared with and informed by relevant knowledge users. Dissemination of findings will also include peer-reviewed publications and conference presentations. The results will offer new insights for supporting patient engagement in consensus-building healthcare initiatives., Protocol Registration: https://osf.io/beqjr., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cellular therapies have been investigated to improve blood flow and prevent amputation in peripheral artery disease with limited efficacy in clinical trials. Alginate-encapsulated mesenchymal stromal cells (eMSCs) demonstrated improved retention and survival and promoted vascular generation in murine hind limb ischemia through their secretome, but large animal evaluation is necessary for human applicability. We sought to determine the efficacy of eMSCs for peripheral artery disease-induced limb ischemia through assessment in our durable swine hind limb ischemia model., Methods and Results: Autologous bone marrow eMSCs or empty alginate capsules were intramuscularly injected 2 weeks post-hind limb ischemia establishment (N=4/group). Improvements were quantified for 4 weeks through walkway gait analysis, contrast angiography, blood pressures, fluorescent microsphere perfusion, and muscle morphology and histology. Capsules remained intact with mesenchymal stromal cells retained for 4 weeks. Adenosine-induced perfusion deficits and muscle atrophy in ischemic limbs were significantly improved by eMSCs versus empty capsules (mean±SD, 1.07±0.19 versus 0.41±0.16, P =0.002 for perfusion ratios and 2.79±0.12 versus 1.90±0.62 g/kg, P =0.029 for ischemic muscle mass). Force- and temporal-associated walkway parameters normalized (ratio, 0.63±0.35 at week 3 versus 1.02±0.19 preligation; P =0.17), and compensatory footfall patterning was diminished in eMSC-administered swine (12.58±8.46% versus 34.85±15.26%; P =0.043). Delivery of eMSCs was associated with trending benefits in collateralization, local neovascularization, and muscle fibrosis. Hypoxia-cultured porcine mesenchymal stromal cells secreted vascular endothelial growth factor and tissue inhibitor of metalloproteinase 2., Conclusions: This study demonstrates the promise of the mesenchymal stromal cell secretome at improving peripheral artery disease outcomes and the potential for this novel swine model to serve as a component of the preclinical pipeline for advanced therapies.

The genome-scale metabolic model (GEM) has emerged as one of the leading modeling approaches for systems-level metabolic studies and has been widely explored for a broad range of organisms and applications. Owing to the development of genome sequencing technologies and available biochemical data, it is possible to reconstruct GEMs for model and non-model microorganisms as well as for multicellular organisms such as humans and animal models. GEMs will evolve in parallel with the availability of biological data, new mathematical modeling techniques and the development of automated GEM reconstruction tools. The use of high-quality, context-specific GEMs, a subset of the original GEM in which inactive reactions are removed while maintaining metabolic functions in the extracted model, for model organisms along with machine learning (ML) techniques could increase their applications and effectiveness in translational research in the near future. Here, we briefly review the current state of GEMs, discuss the potential contributions of ML approaches for more efficient and frequent application of these models in translational research, and explore the extension of GEMs to integrative cellular models.

Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Melanin is one of the representative biomarkers of malignant melanoma and a potential target for diagnosis and therapy. With advancements in chemistry and radiolabeling technologies, promising strides have been made to synthesize radiolabeled melanin-binding molecules for various applications. We present an overview of melanin-targeted radiolabeled molecules and compare their features reported in preclinical studies. Clinical practice and trials are also discussed to elaborate on the safety and validity of the probes, and expanded applications beyond melanoma are reviewed. Melanin-targeted imaging holds potential value in the diagnosis, staging, and prognostic assessment of melanoma and other applications. Melanin-targeted radionuclide therapy possesses immense potential but requires more clinical validation. Furthermore, an intriguing avenue for future research involves expanding the application scope of melanin-targeted probes and exploring their value., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Nectin cell adhesion molecule 4 (nectin-4) is a transmembrane protein overexpressed on a variety of cancers and plays an important role in oncogenic and metastatic processes. The nectin-4-targeted antibody-drug conjugate enfortumab vedotin has been approved for treating locally advanced or metastatic urothelial cancer, but the efficacy in other types of cancer remains to be explored. The aim of this study was to evaluate the feasibility of nectin-4-targeted PET imaging with 68 Ga-N188 as a noninvasive method to quantify membranous nectin-4 expression in multiple tumor types-an approach that may provide insight for patient stratification and treatment selection. Methods: Sixty-two patients with 16 types of cancer underwent head-to-head 68 Ga-N188 and 18 F-FDG PET/CT imaging for initial staging or detection of recurrence and metastases. Correlation between lesion SUV max and nectin-4 expression determined by immunohistochemistry staining was analyzed in 36 of 62 patients. Results: The SUV max of 68 Ga-N188 had a positive correlation with membranous nectin-4 expression in the various tumor types tested ( r = 0.458; P = 0.005), whereas no association was observed between the SUV max and cytoplasmic nectin-4 expression. The detection rates for patient-based analysis of 68 Ga-N188 and 18 F-FDG PET/CT examinations were comparable (95.00% [57/60] vs. 93.33% [56/60]). In patients with pancreatic cancer, 68 Ga-N188 exhibited a potential advantage for detecting residual or locally recurrent tumors; this advantage may assist in clinical decision-making. Conclusion: The correlation between nectin-4-targeted 68 Ga-N188 PET imaging and membranous nectin-4 expression indicates the potential of 68 Ga-N188 as an effective tool for selecting patients who may benefit from enfortumab vedotin treatment. The PET imaging results provided evidence to explore nectin-4-targeted therapy in a variety of tumors. 68 Ga-N188 may improve the restaging of pancreatic cancer but requires further evaluation in a powered, prospective setting., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

In transplantation, hypothermic machine perfusion (HMP) has been shown to be superior to static cold storage (SCS) in terms of functional outcomes. Ex vivo machine perfusion offers the possibility to deliver drugs or other active substances, such as Mesenchymal Stem Cells (MSCs), directly into an organ without affecting the recipient. MSCs are multipotent, self-renewing cells with tissue-repair capacities, and their application to ameliorate ischemia- reperfusion injury (IRI) is being investigated in several preclinical and clinical studies. The aim of this study was to introduce MSCs into a translational model of hypothermic machine perfusion and to test the efficiency and feasibility of this method. Methods: three rodent kidneys, six porcine kidneys and three human kidneys underwent HMP with 1-5 × 10 6 labelled MSCs within respective perfusates. Only porcine kidneys were compared to a control group of 6 kidneys undergoing HMP without MSCs, followed by mimicked reperfusion with whole blood at 37 °C for 2 h for all 12 kidneys. Reperfusion perfusate samples were analyzed for levels of NGAL and IL-β by ELISA. Functional parameters, including urinary output, oxygen consumption and creatinine clearance, were compared and found to be similar between the MSC treatment group and the control group in the porcine model. IL-1β levels were higher in perfusate and urine samples in the MSC group, with a median of 285.3 ng/mL (IQR 224.3-407.8 ng/mL) vs. 209.2 ng/mL (IQR 174.9-220.1), p = 0.51 and 105.3 ng/mL (IQR 71.03-164.7 ng/mL) vs. 307.7 ng/mL (IQR 190.9-349.6 ng/mL), p = 0.16, respectively. MSCs could be traced within the kidneys in all models using widefield microscopy after HMP. The application of Mesenchymal Stem Cells in an ex vivo hypothermic machine perfusion setting is feasible, and MSCs can be delivered into the kidney grafts during HMP. Functional parameters during mimicked reperfusion were not altered in treated kidney grafts. Changes in levels of IL-1β suggest that MSCs might have an effect on the kidney grafts, and whether this leads to a positive or a negative outcome on IRI in transplantation needs to be determined in further experiments.

Objective: Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023., Methods: Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review., Results: A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers., Conclusions: In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer., Competing Interests: Conflicts of interest. None declared.

GRN mutations cause progranulin haploinsufficiency, which eventually leads to frontotemporal dementia (FTD-GRN). PR006 is an investigational gene therapy delivering the granulin gene (GRN) using an adeno-associated virus serotype 9 (AAV9) vector. In non-clinical studies, PR006 transduced neurons derived from induced pluripotent stem cells of patients with FTD-GRN, resulted in progranulin expression and improvement of lipofuscin, lysosomal and neuroinflammation pathologies in Grn-knockout mice, and was well tolerated except for minimal, asymptomatic dorsal root ganglionopathy in non-human primates. We initiated a first-in-human phase 1/2 open-label trial. Here we report results of a pre-specified interim analysis triggered with the last treated patient of the low-dose cohort (n = 6) reaching the 12-month follow-up timepoint. We also include preliminary data from the mid-dose cohort (n = 7). Primary endpoints were safety, immunogenicity and change in progranulin levels in cerebrospinal fluid (CSF) and blood. Secondary endpoints were Clinical Dementia Rating (CDR) plus National Alzheimer's Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) rating scale and levels of neurofilament light chain (NfL). One-time administration of PR006 into the cisterna magna was generally safe and well tolerated. All patients developed treatment-emergent anti-AAV9 antibodies in the CSF, but none developed anti-progranulin antibodies. CSF pleocytosis was the most common PR006-related adverse event. Twelve serious adverse events occurred, mostly unrelated to PR006. Deep vein thrombosis developed in three patients. There was one death (unrelated) occurring 18 months after treatment. CSF progranulin increased after PR006 treatment in all patients; blood progranulin increased in most patients but only transiently. NfL levels transiently increased after PR006 treatment, likely reflecting dorsal root ganglia toxicity. Progression rates, based on the CDR scale, were within the broad ranges reported for patients with FTD. These data provide preliminary insights into the safety and bioactivity of PR006. Longer follow-up and additional studies are needed to confirm the safety and potential efficacy of PR006. ClinicalTrials.gov identifier: NCT04408625 ., (© 2024. The Author(s).)

Opinion Statement: Diffuse large B-cell lymphoma (DLBCL) is a curable disease with variable outcomes due to underlying heterogeneous clinical and molecular features-features that are insufficiently characterized with our current tools. Due to these limitations, treatment largely remains a "one-size-fits-all" approach. Circulating tumor DNA (ctDNA) is a novel biomarker in cancers that is increasingly utilized for risk stratification and response assessment. ctDNA is readily detectable from the plasma of patients with DLBCL but has not yet been incorporated into clinical care to guide treatment. Here, we describe how ctDNA sequencing represents a promising technology in development to personalize the care of patients with DLBCL. We will review the different types of ctDNA assays being studied and the rapidly growing body of evidence supporting the utility of ctDNA in different treatment settings in DLBCL. Risk stratification by estimation of tumor burden and liquid genotyping, molecular response assessment during treatment, and monitoring for measurable residual disease (MRD) to identify therapy resistance and predict clinical relapse are all potential applications of ctDNA. It is time for clinical trials in DLBCL to utilize ctDNA as an integral biomarker for patient selection, response-adapted designs, and surrogate endpoints. As more ctDNA assays become commercially available for routine use, clinicians should consider liquid biopsy when treatment response is equivocal on imaging. Incorporating MRD may also guide decision-making if patients experience severe treatment toxicities. Though important barriers remain, we believe that ctDNA will soon be ready to transition from bench to bedside to individualize treatment for our patients with DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interest None.

Mental health and neurodevelopmental disorders are highly heritable and can affect morbidity and mortality. A large, growing body of evidence has implicated both common and rare variation in the risk of these disorders. Testing for rare variants, such as copy number variants, has been available in clinical practice for some time in the context of developmental disorders. However, until recently, individuals with mental health and neurodevelopmental disorders in the UK have not tended to access genetic counselling and testing. Here, we describe the development of the All Wales Psychiatric Genomics Service, a collaborative effort between psychiatric and clinical genetics services and the first of its kind in the UK. We provide an overview of the structure and function of the service, our referral criteria, a summary of the 40 referrals we have received to date and our future plans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to develop the first machine learning models to predict citation counts and the translational impact, defined as inclusion in guidelines or policy documents, of headache research, and assess which factors are most predictive., Methods: Bibliometric data and the titles, abstracts, and keywords from 8600 publications in three headache-oriented journals from their inception to 31 December 2017 were used. A series of machine learning models were implemented to predict three classes of 5-year citation count intervals (0-5, 6-14 and, >14 citations); and the translational impact of a publication. Models were evaluated out-of-sample with area under the receiver operating characteristics curve (AUC)., Results: The top performing gradient boosting model predicted correct citation count class with an out-of-sample AUC of 0.81. Bibliometric data such as page count, number of references, first and last author citation counts and h-index were among the most important predictors. Prediction of translational impact worked optimally when including both bibliometric data and information from the title, abstract and keywords, reaching an out-of-sample AUC of 0.71 for the top performing random forest model., Conclusion: Citation counts are best predicted by bibliometric data, while models incorporating both bibliometric data and publication content identifies the translational impact of headache research., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The prevalence and healthcare cost of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased alongside the epidemic surge in obesity and Type 2 diabetes. Weight loss through lifestyle modification remains the primary effective therapy for MASLD. Incorporation of mobile technology in lifestyle interventions has been previously found to be efficacious and cost-effective in facilitating weight loss. However, there is a paucity of studies that have successfully translated lifestyle research into clinical service for weight loss to alleviate disease burden. Our study aimed to describe the process of translating a mobile technology-enabled trial into a tertiary hospital outpatient dietetics service for patients with MASLD., Methods: The Iowa Model of Evidence-Based Practice to Improve Quality Care was used as a framework for this paper to guide implementation at the organizational level., Results: Regular engagement of key operational staff and the hospital management team facilitated open discussions of the challenges faced and enabled rapid implementation of strategies that contributed to the smooth piloting of the service. A service adoption rate of 81% was achieved. Preliminary outcome evaluation found that the percentage of patients achieving ≥ 5% weight loss from baseline at 6 months was comparable at 54% and 52% for the service and trial groups, respectively., Conclusions: Evaluation of the implementation process found that a hybrid model of care (in-person consultation supplemented with app coaching) preserved interpersonal connections while maximizing the convenience and scalability of mobile app-enabled service. Although high digital acceptance and adoption rates propelled by COVID-19-supported telehealth, it is prudent to assess patient's access to technology and digital literacy and offer resources to help them benefit from telehealth services., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

In August of 2023, the National Academies of Science, Engineering, and Medicine published a timely report titled "Toward Equitable Innovation in Health and Medicine: A Framework." Here, we review some of the key contributions of the report, focusing on two dimensions of equity: input equity and deployment equity. We then use the example of new gene therapies to treat sickle cell disease (SCD) as a case study of input and deployment equity in translational research. The SCD case study illustrates the need for a kind of translational bioethics with deep understanding of lived experiences and clinical realities as well as a high degree of economic and policy sophistication., (© 2024 by The Hastings Center. All rights reserved.)

Acute kidney injury (AKI) constitutes a significant public health concern, with limited therapeutic options to mitigate injury or expedite recovery. A novel therapeutic approach, local renal treatment, encompassing pharmacotherapy and surgical interventions, has exhibited positive outcomes in AKI management. Peri-renal administration, employing various delivery routes, such as the renal artery, intrarenal, and subcapsular sites, has demonstrated superiority over peripheral intravenous infusion. This review evaluates different drug delivery methods, analyzing their benefits and limitations, and proposes potential improvements. Renal decapsulation, particularly with the availability of minimally invasive techniques, emerges as an effective procedure warranting renewed consideration for AKI treatment. The potential synergistic effects of combined drug delivery and renal decapsulation could further advance AKI therapies. Clinical studies have already begun to leverage the benefits of local renal treatments, and with ongoing technological advancements, these modalities are expected to increasingly outperform systemic intravenous therapy.

Background: Due to the high disease burden, the early onset and often long-term trajectories mental disorders are among the most widespread diseases with growing significance. The German Center for Mental Health (DZPG) was established to enhance research conditions and expedite the translation of clinically relevant findings into practice., Objective: The aim of the DZPG is to optimize mental healthcare in Germany, influence modifiable social causes and to develop best practice models of care for vulnerable groups. It seeks to promote mental health and resilience, combat the stigmatization associated with mental disorders, and contribute to the enhancement of treatment across all age groups., Material and Methods: The DZPG employs a translational research program that accelerates the translation of basic research findings into clinical studies and general practice. University hospitals and outpatient departments, other university disciplines, and extramural research institutions are working together to establish a collaboratively coordinated infrastructure for accelerated translation and innovation., Research Priorities: The research areas encompass 1) the interaction of somatic and mental risk and resilience factors and disorders across the lifespan, 2) influencing relevant modifiable environmental factors and 3) based on this personalized prevention and intervention., Conclusion: The DZPG aims to develop innovative preventive and therapeutic tools that enable an improvement in care for individuals with mental disorders. It involves a comprehensive integration of experts with experience at all levels of decision-making and employs trilogue and participatory approaches in all research projects., (© 2024. The Author(s).)

Objective: To describe the implementation of the international guidelines for the early diagnosis of cerebral palsy (CP) and engagement in the screening process in an Australian cohort of infants with neonatal risk factors for CP., Study Design: Prospective cohort study of infants with neonatal risk factors recruited at <6 months corrected age from 11 sites in the states of Victoria, New South Wales, and Queensland, Australia. First, we implemented a multimodal knowledge translation strategy including barrier identification, technology integration, and special interest groups. Screening was implemented as follows: infants with clinical indications for neuroimaging underwent magnetic resonance imaging and/or cranial ultrasound. The Prechtl General Movements Assessment (GMA) was recorded clinically or using an app (Baby Moves). Infants with absent or abnormal fidgety movements on GMA videos were offered further assessment using the Hammersmith Infant Neurological Examination (HINE). Infants with atypical findings on 2/3 assessments met criteria for high risk of CP., Results: Of the 597 infants (56% male) recruited, 95% (n = 565) received neuroimaging, 90% (n = 537) had scorable GMA videos (2% unscorable/8% no video), and 25% (n = 149) HINE. Overall, 19% of the cohort (n = 114/597) met criteria for high risk of CP, 57% (340/597) had at least 2 normal assessments (of neuroimaging, GMA or HINE), and 24% (n = 143/597) had insufficient assessments., Conclusions: Early CP screening was implemented across participating sites using a multimodal knowledge translation strategy. Although the COVID-19 pandemic affected recruitment rates, there was high engagement in the screening process. Reasons for engagement in early screening from parents and clinicians warrant further contextualization and investigation., Competing Interests: Declaration of Competing Interest This work was supported by the National Health and Medical Research Council Partnership grant AP1152800. Training on GMA and HINE and implementation of the QEDIN network is funded by the NHMRCCentre of Research Excellence the Australian-CP-Clinical Trials Network (NHMRC1078851) and for the QLD Early Detection and Early Intervention Network by QLD Department of Innovation Advance QLD Program16-103. RB is supported by an NHMRC Investigator grant (NHMRC1105038). A.J.S. and C.M. are tutors with the General Movements Trust. A.J.S. is on the editorial board of the Journal of Pediatrics. The other authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: The Translational Science Benefit Model (TSBM) was developed to broadly capture systematic measures of health and societal benefits from scientific research, beyond traditional outcome measures. We aimed to develop a systematic process for the application of the TSBM and to then provide an example of a novel application of the TSBM to an ongoing Return-to-Learn (RTL) after youth concussion project involving partnerships with community stakeholders., Methods: We invited investigators, project advisory board, and participants of the RTL project to participate in a modified Delphi process. We first generated a list of potential translational benefits using the indicators of the TSBM as guideposts. We then prioritized the benefits on an adapted Eisenhower matrix., Results: We invited 35 concussion care or research experts to participate, yielding 20 ranked translational benefits. Six of these recommendations were ranked high priority, six were regarded as investments, and eight were ranked as either low yield or low priority., Discussion: This study found that activities such as education and training of stakeholders, development of policy and consensus statements, and innovation in dissemination, were perceived as higher priority than other activities. Our approach using a modified Delphi process and incorporating the TSBM can be replicated to generate and prioritize potential benefits to society from research studies., Competing Interests: The authors report no relevant conflicts of interest.

Purpose of Review: To discuss the recent discoveries and limitations of the available literature on emerging circulating biomarkers of cancer cachexia., Recent Findings: Studies on circulating factors in cancer cachexia show promising alternatives for diagnosing the syndrome in a minimally invasive manner in the clinic setting, as well as potential targets for cancer cachexia treatment. Factors secreted by the tumor and the adipose tissue, such as extracellular vesicles and soluble proteins, respectively, have been shown to either directly induce wasting in vitro and in vivo or to be altered in the cachectic phenotype. The detection and characterization of circulating cells allows detection of the precachectic stage and the levels of the soluble immune checkpoint protein programmed death ligand-1 (PD-L1) are correlated with the presence of the hallmarks of cancer cachexia., Summary: Structural, molecular, and metabolic alterations have been observed in various tissues, revealing the occurrence of sustained inter-compartment crosstalk in cachectic patients. Early diagnosis of cancer cachexia becomes crucial to avoid the establishment of refractory cachexia through the implementation of interventions that may attenuate systemic inflammation and muscle loss. More studies on human cancer cachexia are required in order to address the recently discovered cachexia-associated circulating factors' value as biomarkers of the syndrome., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Knowledge Translation (KT) aims to convey novel ideas to relevant stakeholders, motivating their response or action to improve people's health. Initially, the KT literature focused on evidence-based medicine, applying findings from laboratory and clinical research to disease diagnosis and treatment. Since the early 2000s, the scope of KT has expanded to include decision-making with health policy implications.This systematic scoping review aims to assess the evolving knowledge-to-policy concepts, that is, macro-level KT theories, models and frameworks (KT TMFs). While significant attention has been devoted to transferring knowledge to healthcare settings (i.e. implementing health policies, programmes or measures at the meso-level), the definition of 'context' in the realm of health policymaking at the macro-level remains underexplored in the KT literature. This study aims to close the gap.A total of 32 macro-level KT TMFs were identified, with only a limited subset of them offering detailed insights into contextual factors that matter in health policymaking. Notably, the majority of these studies prompt policy changes in low- and middle-income countries and received support from international organisations, the European Union, development agencies or philanthropic entities., (© 2024. The Author(s).)

Systemic sclerosis (SSc) is a heterogeneous disease characterized by autoimmunity, vasculopathy, and fibrosis which affects the skin and internal organs. One key aspect of SSc vasculopathy is pulmonary arterial hypertension (SSc-PAH) which represents a leading cause of morbidity and mortality in patients with SSc. The pathogenesis of pulmonary hypertension is complex, with multiple vascular cell types, inflammation, and intracellular signaling pathways contributing to vascular pathology and remodeling. In this review, we focus on shared molecular features of pulmonary hypertension and those which make SSc-PAH a unique entity. We highlight advances in the understanding of the clinical and translational science pertinent to this disease. We first review clinical presentations and phenotypes, pathology, and novel biomarkers, and then highlight relevant animal models, key cellular and molecular pathways in pathogenesis, and explore emerging treatment strategies in SSc-PAH.

The blood transcriptome of malaria patients has been used extensively to elucidate the pathophysiological mechanisms and host immune responses to disease, identify candidate diagnostic and prognostic biomarkers, and reveal new therapeutic targets for drug discovery. This review gives a high-level overview of the three main translational applications of these studies (diagnostics, prognostics, and therapeutics) by summarising recent literature and outlining the main limitations and future directions of each application. It highlights the need for consistent and accurate definitions of disease states and subject groups and discusses how prognostic studies must distinguish clearly between analyses that attempt to predict future disease states and those which attempt to discriminate between current disease states (classification). Lastly it examines how many promising therapeutics fail due to the choice of imperfect animal models for pre-clinical testing and lack of appropriate validation studies in humans, and how future transcriptional studies may be utilised to overcome some of these limitations., (© 2024 The Author(s).)

Background and Objectives: Without strategic actions in its support, the translation of scientific research evidence into health policy is often absent or delayed. This review systematically maps and assesses national-level strategic documents in the field of knowledge translation (KT) for health policy, and develops a practical template that can support Evidence-informed Policy Network (EVIPNet) Europe countries in producing national strategies for evidence-informed policy-making., Methods: Websites of organizations with strategic responsibilities in KT were electronically searched, on the basis of pre-defined criteria, in July-August 2017, and an updated search was carried out in April-June 2021. We included national strategies or elements of national strategies that dealt with KT activities, as well as similar strategies of individual institutions with a national policy focus. Two reviewers screened the strategies for inclusion. Data were analysed using qualitative content analysis., Results: A total of 65 unique documents were identified, of which 17 were eligible and analysed for their structure and content. Of the 17, 1 document was a national health KT action plan and 6 documents were institution-level KT strategies. The remaining 10 strategies, which were also included were 2 national health strategies, 5 national health research strategies and 3 national KT strategies (not specific to the field of health alone). In all, 13 structural elements and 7 major themes of health policy KT strategies were identified from the included documents., Conclusion: KT in health policy, as emerged from the national strategies that our mapping identified, is based on the production and accessibility of policy-relevant research, its packaging for policy-making and the activities related to knowledge exchange. KT strategies may play different roles in the complex and context-specific process of policy-making. Our findings show that the main ideas of health-specific evidence-informed policy literature appear in these strategies, but their effectiveness depends on the way stakeholders use them. Specific knowledge-brokering institutions and organizational capacity, advocacy about the use of evidence, and close collaboration and co-decision-making with key stakeholders are essential in furthering the policy uptake of research results., (© 2024. World Health Organization.)

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis, while atherosclerosis, with its inflammatory microenvironment, can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review, we aim to summarize the state of the art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology and exert a positive impact on precision cardiology and cardio-oncology.

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoint resources and abstraction algorithms), and benchmarks (e.g., prebuilt KGs). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 different large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability., (© 2024. The Author(s).)

Boron neutron capture therapy (BNCT) is a type of targeted particle radiation therapy with potential applications at the cellular level. Spinal cord gliomas (SCGs) present a substantial challenge owing to their poor prognosis and the lack of effective postoperative treatments. This study evaluated the efficacy of BNCT in a rat SCGs model employing the Basso, Beattie, and Bresnahan (BBB) scale to assess postoperative locomotor activity. We confirmed the presence of adequate in vitro boron concentrations in F98 rat glioma and 9L rat gliosarcoma cells exposed to boronophenylalanine (BPA) and in vivo tumor boron concentration 2.5 h after intravenous BPA administration. In vivo neutron irradiation significantly enhanced survival in the BNCT group when compared with that in the untreated group, with a minimal BBB scale reduction in all sham-operated groups. These findings highlight the potential of BNCT as a promising treatment option for SCGs., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The spinocerebellar ataxias (SCA) comprise a group of inherited neurodegenerative diseases. Machado-Joseph Disease (MJD) or spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant form, caused by the expansion of CAG repeats within the ataxin-3 (ATXN3) gene. This mutation results in the expression of an abnormal protein containing long polyglutamine (polyQ) stretches that confers a toxic gain of function and leads to misfolding and aggregation of ATXN3 in neurons. As a result of the neurodegenerative process, SCA3 patients are severely disabled and die prematurely. Several screening approaches, e.g., druggable genome-wide and drug library screenings have been performed, focussing on the reduction in stably overexpressed ATXN3(polyQ) protein and improvement in the resultant toxicity. Transgenic overexpression models of toxic ATXN3, however, missed potential modulators of endogenous ATXN3 regulation. In another approach to identify modifiers of endogenous ATXN3 expression using a CRISPR/Cas9-modified SK-N-SH wild-type cell line with a GFP - T2A - luciferase ( LUC ) cassette under the control of the endogenous ATXN3 promotor, four statins were identified as potential activators of expression. We here provide an overview of the high throughput screening approaches yet performed to find compounds or genomic modifiers of ATXN3(polyQ) toxicity in different SCA3 model organisms and cell lines to ameliorate and halt SCA3 progression in patients. Furthermore, the putative role of cholesterol in neurodegenerative diseases (NDDs) in general and SCA3 in particular is discussed.

The objective of this article is to provide a brief overview of the critical analysis and design of unique and perhaps less common methodologies in podiatric science. These include basic science translational designs, cadaveric investigations, gait analyses, dermatologic studies, and database analysis. The relative advantages, disadvantages, and inherent limitations are reviewed with an intention to improve the interpretation of results and advance future foot and ankle scientific endeavors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives., (© 2024. The Author(s).)

Background: Basic scientists have used preclinical animal models to explore mechanisms driving human diseases for decades, resulting in thousands of publications, each supporting causative inferences. Despite substantial advances in the mechanistic construct of disease, there has been limited translation from individual studies to advances in clinical care. An integrated approach to these individual studies has the potential to improve translational success., Methods: Using atherosclerosis as a test case, we extracted data from the 2 most common mouse models of atherosclerosis (ApoE [apolipoprotein E]-knockout and LDLR [low-density lipoprotein receptor]-knockout). We restricted analyses to manuscripts published in 2 well-established journals, Arteriosclerosis, Thrombosis, and Vascular Biology and Circulation , as of query in 2021. Predefined variables including experimental conditions, intervention, and outcomes were extracted from each publication to produce a preclinical atherosclerosis database., Results: Extracted data include animal sex, diet, intervention type, and distinct plaque pathologies (size, inflammation, and lipid content). Procedures are provided to standardize data extraction, attribute interventions to specific genes, and transform the database for use with available transcriptomics software. The database integrates hundreds of genes, each directly tested in vivo for causation in a murine atherosclerosis model. The database is provided to allow the research community to perform integrated analyses that reflect the global impact of decades of atherosclerosis investigation., Conclusions: This database is provided as a resource for future interrogation of sub-data sets associated with distinct plaque pathologies, cell type, or sex. We also provide the methods and software needed to expand this data set and apply this approach to the extensive repository of peer-reviewed data utilizing preclinical models to interrogate mechanisms of diverse human diseases., Competing Interests: Disclosures Dr Beckman has consulted for Janssen, JanOne, and Novartis and received grant funding from Bristol Myers Squibb. Dr Jaffe has consulted for Boehringer Ingelheim. The other authors report no conflicts.