Analysis of animal-to-human translation shows that only 5% of animal-tested therapeutic interventions obtain regulatory approval for human applications.

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in animal studies translate to humans. We aimed to assess 2 measures of translation across various biomedical fields: (1) The proportion of therapies which transition from animal studies to human application, including involved timeframes; and (2) the consistency between animal and human study results. Thus, we conducted an umbrella review, including English systematic reviews that evaluated the translation of therapies from animals to humans. Medline, Embase, and Web of Science Core Collection were searched from inception until August 1, 2023. We assessed the proportion of therapeutic interventions advancing to any human study, a randomized controlled trial (RCT), and regulatory approval. We meta-analyzed the concordance between animal and human studies. The risk of bias was probed using a 10-item checklist for systematic reviews. We included 122 articles, describing 54 distinct human diseases and 367 therapeutic interventions. Neurological diseases were the focus of 32% of reviews. The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval. Notably, our meta-analysis showed an 86% concordance between positive results in animal and clinical studies. The median transition times from animal studies were 5, 7, and 10 years to reach any human study, an RCT, and regulatory approval, respectively. We conclude that, contrary to widespread assertions, the rate of successful animal-to-human translation may be higher than previously reported. Nonetheless, the low rate of final approval indicates potential deficiencies in the design of both animal studies and early clinical trials. To ameliorate the efficacy of translating therapies from bench to bedside, we advocate for enhanced study design robustness and the reinforcement of generalizability.

Translation from Preclinical Research to Clinical Trials: Transdermal Drug Delivery for Neurodegenerative and Mental Disorders.

Neurodegenerative diseases (NDs), particularly dementia, provide significant problems to worldwide healthcare systems. The development of therapeutic materials for various diseases has a severe challenge in the form of the blood-brain barrier (BBB). Transdermal treatment has recently garnered widespread favor as an alternative method of delivering active chemicals to the brain. This approach has several advantages, including low invasiveness, self-administration, avoidance of first-pass metabolism, preservation of steady plasma concentrations, regulated release, safety, efficacy, and better patient compliance. Topics include the transdermal method for therapeutic NDs, their classification, and the mechanisms that allow the medicine to enter the bloodstream through the skin. The paper also discusses the obstacles and potential outcomes of transdermal therapy, emphasizing the benefits and drawbacks of different approaches.

Using the Translating Research into Practice framework to develop a diabetes prevention intervention in primary care: a mixed-methods study.

BACKGROUND: Pre-diabetes affects one-third of US adults and increases the risk of type 2 diabetes. Effective evidence-based interventions, such as the Diabetes Prevention Program, are available, but a gap remains in effectively translating and increasing uptake of these interventions into routine care. METHODS: We applied the Translating Research into Practice (TRiP) framework to guide three phases of intervention design and development for diabetes prevention: (1) summarise the evidence, (2) identify local barriers to implementation and (3) measure performance. In phase 1, we conducted a retrospective cohort analysis of linked electronic health record claims data to evaluate current practices in the management of pre-diabetes. In phase 2, we conducted in-depth interviews of 16 primary care physicians, 7 payor leaders and 31 patients to elicit common barriers and facilitators for diabetes prevention. In phase 3, using findings from phases 1 and 2, we developed the core elements of the intervention and performance measures to evaluate intervention uptake. RESULTS: In phase 1 (retrospective cohort analysis), we found few patients with pre-diabetes received diabetes prevention interventions. In phase 2 (stakeholder engagement), we identified common barriers to include a lack of knowledge about pre-diabetes among patients and about the Diabetes Prevention Program among clinicians. In phase 3 (intervention development), we developed the START Diabetes Prevention Clinical Pathway as a systematic change package to address barriers and facilitators identified in phases 1 and 2, performance measures and a toolkit of resources to support the intervention components. CONCLUSIONS: The TRiP framework supported the identification of evidence-based care practices for pre-diabetes and the development of a well-fitted, actionable intervention and implementation plan designed to increase treatment uptake for pre-diabetes in primary care settings. Our change package can be adapted and used by other health systems or clinics to target prevention of diabetes or other related chronic conditions.

Health research evidence: its current usage in health planning, determinants and readiness to use knowledge translation tools among health planning teams in Tanzania-an exploratory mixed-methods study protocol.

INTRODUCTION: Achieving universal health coverage requires using research evidence to inform decision-making. However, little information is available on the use of research evidence in planning in lower middle-income countries, including Tanzania. This paper presents a protocol that aims to investigate the usage of research evidence in health planning, determinants and readiness of the planning team members to use knowledge translation tools in Tanzania. METHODS AND ANALYSIS: This study will employ a sequential exploratory mixed-methods design, with participants selected from national, regional and council levels. Qualitative data will be collected through a maximum of 52 in-depth interviews and 12 focused group discussions until saturation. To collect quantitative data, a structured questionnaire will be used to survey 422 participants, and a document review will be conducted from health facilities. Qualitative data will be analysed using thematic analysis, while descriptive and inferential analyses will be employed for quantitative data. ETHICS AND DISSEMINATION: The study participants will provide written informed consent, and all recorded data will be stored on a secured research server accessible only to the investigators. Ethical approval has been obtained from the University of Dodoma Research Ethics Committee (ref. MA.84/261/02/'A'/64/91). The findings of this study will inform policymakers, researchers and implementers in the country on the use of research evidence in decision-making. We will disseminate our findings through publications, conferences, workshops and interactive communication with national, regional, council and health facility planning teams.

Fear attenuation collaborations to optimize translation.

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Selection of knowledge translation strategies to implement best practices on nonpharmacological prevention of delirium in intensive care unit / Sélection de stratégies de transfert des connaissances visant à implanter les pratiques recommandées de prévention non pharmacologiques du délirium en soins intensifs.

Background: Delirium prevention in the ICU should focus on a non-pharmacological approach. However, these recommendations are not always applied by care providers. Objective: To select knowledge translation strategies to facilitate the implementation of non-pharmacological best practices to prevent delirium in the ICU. Method: A consensus study was conducted. Barriers and facilitators to the implementation of nonpharmacological methods, and knowledge translation strategies, were identified in two nominal groups. A context assessment was also carried out. Nine professionals and one patient-partner participated. Results: The barriers and facilitators on which consensus was reached were most frequently related to environmental context and resources, intention, and knowledge. The areas of organizational context with the highest levels of agreement were interpersonal relations, culture and leadership. Consequently, knowledge translation strategies were selected to facilitate practices, as well as to modify the environment and improve knowledge. Conclusion: A structured method was used during this study to guide the selection of knowledge translation strategies. The application of these strategies could potentially improve clinical practice in intensive care.

Introduction: La prévention du délirium aux soins intensifs devrait être axée sur les méthodes non pharmacologiques. Toutefois, ce type de recommandation n'est pas toujours appliqué. Objectif: Sélectionner des stratégies de transfert des connaissances afin de faciliter l'implantation des pratiques non pharmacologiques pouvant prévenir le délirium en soins intensifs. Méthode: Une étude de consensus a été réalisée autour de deux thèmes. Deux groupes nominaux ont été constitués pour identifier les barrières et les facilitateurs à l'implantation des méthodes et les stratégies de transfert des connaissances. Une évaluation du contexte a aussi été réalisée. Neuf professionnels et une patiente-partenaire ont participé. Résultats: Les barrières et les facilitateurs ayant fait l'objet d'un consensus étaient plus fréquemment reliés au contexte environnemental et aux ressources, à l'intention et aux connaissances. Les domaines du contexte organisationnel qui ont obtenu le plus haut niveau d'accord sont les relations interpersonnelles, la culture et le leadership. Conséquemment, des stratégies de transfert des connaissances pour faciliter les pratiques, modifier l'environnement et améliorer les connaissances ont été sélectionnées. Conclusion: Une méthode structurée a été utilisée afin de guider la sélection de stratégies de transfert des connaissances. L'application de ces stratégies pourrait potentiellement améliorer la pratique clinique en soins intensifs.

Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges.

Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.

Recent Translational Research Models of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.

Recent advancements in cartilage tissue engineering innovation and translation.

Articular cartilage was expected to be one of the first successfully engineered tissues, but today, cartilage repair products are few and they exhibit considerable limitations. For example, of the cell-based products that are available globally, only one is marketed for non-knee indications, none are indicated for severe osteoarthritis or rheumatoid arthritis, and only one is approved for marketing in the USA. However, advances in cartilage tissue engineering might now finally lead to the development of new cartilage repair products. To understand the potential in this field, it helps to consider the current landscape of tissue-engineered products for articular cartilage repair and particularly cell-based therapies. Advances relating to cell sources, bioactive stimuli and scaffold or scaffold-free approaches should now contribute to progress in therapeutic development. Engineering for an inflammatory environment is required because of the need for implants to withstand immune challenge within joints affected by osteoarthritis or rheumatoid arthritis. Bringing additional cartilage repair products to the market will require an understanding of the translational vector for their commercialization. Advances thus far can facilitate the future translation of engineered cartilage products to benefit the millions of patients who suffer from cartilage injuries and arthritides.

Updates in Translational Science for Esophageal and Gastric Cancers.

In this article, the authors summarize the current state of translational science for esophageal and gastric cancers. The available targeted therapies, immunotherapies, and recently discovered molecular targets are reviewed. The authors introduce circulating tumor deoxyribonucleic acid and its promise as a biomarker to detect disease recurrence. The authors present patient-derived organoids as a new model for studying carcinogenesis and treatment responses. Finally, we discuss the implications of organoid models for precision oncology and describe exciting new work applying gene editing technology to organoids and studying tumor-microenvironment interactions using 3-dimensional co-culture systems.

Time for Medicine and Public Health to Leave Platform X.

Unlabelled: For more than 50 years, digital technologies have been employed for the creation and distribution of knowledge in health services. In the last decade, digital social media have been developed for applications in clinical decision support and population health monitoring. Recently, these technologies have also been used for knowledge translation, such as in the process where research findings created in academic settings are established as evidence and distributed for use in clinical practice, policy making, and health self-management. To date, it has been common for medical and public health institutions to have social media accounts for the dissemination of novel research findings and to facilitate conversations about these findings. However, recent events such as the transformation of the microblog Twitter to platform X have brought to light the need for the social media industry to exploit user data to generate revenue. In this viewpoint, it is argued that a redirection of social media use is required in the translation of knowledge to action in the fields of medicine and public health. A new kind of social internet is currently forming, known as the "fediverse," which denotes an ensemble of open social media that can communicate with each other while remaining independent platforms. In several countries, government institutions, universities, and newspapers use open social media to distribute information and enable discussions. These organizations control their own channels while being able to communicate with other platforms through open standards. Examples of medical knowledge translation via such open social media platforms, where users are less exposed to disinformation than in general platforms, are also beginning to appear. The current status of the social media industry calls for a broad discussion about the use of social technologies by health institutions involving researchers and health service practitioners, academic leaders, scientific publishers, social technology providers, policy makers, and the public. This debate should not primarily take place on social media platforms but rather at universities, in scientific journals, at public seminars, and other venues, allowing for the transparent and undisturbed communication and formation of opinions.

New developments in pre-clinical models of ALS to guide translation.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder in which selective death of motor neurons leads to muscle weakness and paralysis. Most research has focused on understanding and treating monogenic familial forms, most frequently caused by mutations in SOD1, FUS, TARDBP and C9orf72, although ALS is mostly sporadic and without a clear genetic cause. Rodent models have been developed to study monogenic ALS, but despite numerous pre-clinical studies and clinical trials, few disease-modifying therapies are available. ALS is a heterogeneous disease with complex underlying mechanisms where several genes and molecular pathways appear to play a role. One reason for the high failure rate of clinical translation from the current models could be oversimplification in pre-clinical studies. Here, we review advances in pre-clinical models to better capture the heterogeneous nature of ALS and discuss the value of novel model systems to guide translation and aid in the development of precision medicine.

Photobiomodulation in experimental models of Alzheimer's disease: state-of-the-art and translational perspectives.

Alzheimer's disease (AD) poses a significant public health problem, affecting millions of people across the world. Despite decades of research into therapeutic strategies for AD, effective prevention or treatment for this devastating disorder remains elusive. In this review, we discuss the potential of photobiomodulation (PBM) for preventing and alleviating AD-associated pathologies, with a focus on the biological mechanisms underlying this therapy. Future research directions and guidance for clinical practice for this non-invasive and non-pharmacological therapy are also highlighted. The available evidence indicates that different treatment paradigms, including transcranial and systemic PBM, along with the recently proposed remote PBM, all could be promising for AD. PBM exerts diverse biological effects, such as enhancing mitochondrial function, mitigating the neuroinflammation caused by activated glial cells, increasing cerebral perfusion, improving glymphatic drainage, regulating the gut microbiome, boosting myokine production, and modulating the immune system. We suggest that PBM may serve as a powerful therapeutic intervention for AD.

Mitigating animal methods bias to reduce animal use and improve biomedical translation.

Nonanimal biomedical research methods have advanced rapidly over the last decade making them the first-choice model for many researchers due to improved translatability and avoidance of ethical concerns. Yet confidence in novel nonanimal methods is still being established and they remain a small portion of nonclinical biomedical research, which can lead peer reviewers to evaluate animal-free studies or grant proposals in a biased manner. This "animal methods bias" is the preference for animal-based research methods where they are not necessary or where nonanimal-based methods are suitable. It affects the fair consideration of animal-free biomedical research, hampering the uptake and dissemination of these approaches by putting pressure on researchers to conduct animal experiments and potentially perpetuating the use of poorly translatable model systems. An international team of researchers and advocates called the Coalition to Illuminate and Address Animal Methods Bias (COLAAB) aims to provide concrete evidence of the existence and consequences of this bias and to develop and implement solutions towards overcoming it. The COLAAB recently developed the first of several mitigation tools: the Author Guide for Addressing Animal Methods Bias in Publishing, which is described herein along with broader implications and future directions of this work.

A Translational Case Study of a Multisite COVID-19 Public Health Intervention Across Sequenced Research Trials: Embedding Implementation in a Community Engagement Phased Framework.

Through a COVID-19 public health intervention implemented across sequenced research trials, we present a community engagement phased framework that embeds intervention implementation: (1) consultation and preparation, (2) collaboration and implementation, and (3) partnership and sustainment. Intervention effects included mitigation of psychological distress and a 0.28 increase in the Latinx population tested for SARS-CoV-2. We summarize community engagement activities and implementation strategies that took place across the trials to illustrate the value of the framework for public health practice and research. (Am J Public Health. 2024;114(S5):S396-S401. https://doi.org/10.2105/AJPH.2024.307669).

Single-cell and spatial alterations of neural cells and circuits in clinical and translational medicine.

The spatiotemporal heterogeneity of neurons, circuits and regulators is being uncovered at a single-cell level, from single-cell gene expression to functional regulations. The classifications, architectonics and functional communications amongst neural cells and circuits within the brain can be clearly delineated using single-cell multiomics and transomics. This Editorial highlights the spatiotemporal heterogeneity of neurons and circuits as well as regulators, initiates the translation of neuronal diversity and spatial organisation at single-cell levels into clinical considerations, and enables the discovery and development of new therapies for neurological diseases. It is predicted that single-cell and spatial multiomics will be integrated with metabolomic profiles and corresponding gene epigenetic modifications. The interactions amongst DNAs, RNAs and proteins in a cell provide details of intracellular functional regulations and new opportunities for the translation of temporospatial diversity of neural cell subtypes/states into clinical practice. The application of single-cell multiomics with four-dimensional genome to the human pathological brain will lead us to a new milestone of the diagnosis and treatment.

Bridging the gap between in vitro and in vivo models: a way forward to clinical translation of mitochondrial transplantation in acute disease states.

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment. In this review, we present a summary of CWG conclusions related to these three issues and provide an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials.

404-error "Disease not found": Unleashing the translational potential of -omics approaches beyond traditional disease classification in heart failure research.

The emergence of personalized medicine, facilitated by the progress in -omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of -omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi-omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of 'one size fits all'. Our review examines how omics can enhance understanding of heart failure's molecular foundations and contribute to a more comprehensive disease classification. We draw attention to the current state of medical practice that only relies on clinical evidence and a number of standard laboratory tests. At the same time, we propose a shift towards a universal approach that uses quantitative data from multi-omics to unravel complex molecular interactions. The discussion centres around the potential of the transition as a means to enhance individual risk assessment and emphasizes management within clinical settings. While the use of omics in cardiovascular research is not recent, many past studies have focused only on a single omics approach. In order to achieve a better understanding of disease mechanisms, we explore more holistic approaches using genomics, transcriptomics, epigenomics, and proteomics. This review concludes with a call to action to adopt multi-omics in clinical trials and practice to pave the way for more personalized disease management and more effective heart failure interventions.