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In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence , biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.

Plastic surgeons have used the reconstructive ladder for many decades as a standard directory for complex trauma reconstruction with the goal of repairing body structures and restoring functionality. This consists of different surgical maneuvers, such as secondary intention and direct tissue closure, as well as more complex methods such as local tissue transfer and free flap. The reconstructive ladder represents widely known options achievable for tissue reconstruction and wound closure that puts at the bottom rung the simplest methods of reconstruction and strengthens the complexity by moving upward. Regenerative medicine and surgery constitute a quickly spreading area of translational research that can be employed by minimally invasive surgical strategies, with the aim of regenerating cells and tissues in vivo in order to reestablish normal function through the intrinsic potential of cells, in combination with biomaterials and appropriate biochemical stimuli. These translational procedures have the aim of creating an appropriate microenvironment capable of supporting the physiological cellular function to generate the desired cells or tissues and to generate parenchymal, stromal, and vascular components on demand, and above all to produce intelligent materials capable of determining the fate of cells. Smart technologies have been grown that give extra “rungs” on the classic reconstructive ladder to integrate a more holistic, patient-based approach with improved outcomes. This commentary presents the evolution of the traditional concept of the reconstructive ladder in the field of plastic surgery into a new course with the aim of achieving excellent results for soft tissue reconstruction by applying innovative technologies and biologically active molecules for a wide range of surgical diseases.

Background First-in-human trials mark a significant turning point in translational research, with novel therapies being tested in humans for the first time. Who should be included in FIH trials is a topic of ongoing debate amongst researchers, clinicians, ethicists, and sponsors. Yet, no comprehensive overview of the literature on this topic has been constructed before. Methods A systematic review of reasons was conducted, following the methodology outlined by Stretch and Sofaer for conducting systematic reviews of argument-based literature. Six online databases were consulted across various disciplines, including medicine (PubMed and Embase), philosophy (The Philosopher’s Index and PhilPapers), and multidisciplinary studies (Web of Science and Academic Search Premier). Additionally, relevant books and book chapters were identified through the library of Leiden University. After data extraction and analysis, 80 publications were included. Results 181 reasons were identified amongst six potential participant categories: healthy volunteers, patients (general), patients with less advanced-stage diseases, patients with more advanced-stage diseases, vulnerable populations, and diverse participant groups. These reasons relate to six themes: non-maleficence, beneficence, scientific value, efficiency, respect for persons, and justice. This review highlights multiple challenges in the existing literature, including ambiguous or poorly defined reasons and unspecified use of moral theory, framework, or method, the use of beneficence as an important theme for including participants in FIH trials, and the complexity of identifying and defining vulnerable populations. Conclusions This review provides the first comprehensive overview of the reasons for and against including potential participant groups in FIH trials. The results highlight considerations that are relevant to reflect upon when determining and justifying participant selection for FIH trials. Additionally, this review offers guidance for further normative inquiry.

Background This study aimed to explore the collaborative relationship in translational medical research from the perspective of clinicians in China. The findings are expected to help practitioners optimize and experience the greatest advantages of collaboration. Methods We conducted a national internet-based survey from July 29 to October 12, 2020. Of the 806 responses, 804 were completed with valid responses (valid response rate = 99.8%). The collected data were presented as descriptive statistics and analyzed using nonparametric tests (including the Wilcoxon rank test and Kruskal–Wallis H test) and stepwise logistic regression. Results Of the 804 participants, 733 were either willing or very willing to collaborate in translational medical research. Clinicians’ willingness was influenced by their current research type, role in current translational medical research, burdens of their present research, preferred partners for collaboration at the institutional or individual level, and preferences for independent or dependent relationships. Conclusions Clinicians should evaluate their time, role, burdens, personal preferences for research relationships, and appropriate partners based on their current translational medical research and its goals, before deciding to collaborate.

This paper is a report of recommendations for addressing translational challenges in amyloid disease research. They were developed during and following an international online workshop organized by the LINXS Institute of Advanced Neutron and X-Ray Science in March 2021. Key suggestions include improving cross-cultural communication between basic science and clinical research, increasing the influence of scientific societies and journals (vis-à-vis funding agencies and pharmaceutical companies), improving the dissemination of negative results, and strengthening the ethos of science.

Breakdown of blood-brain barrier, formed mainly by brain microvascular endothelial cells (BMECs), represents the major cause of mortality during early phases of ischemic strokes. Hence, discovery of novel agents that can effectively replace dead or dying endothelial cells to restore blood-brain barrier integrity is of paramount importance in stroke medicine. Although endothelial progenitor cells (EPCs) represent one such agents, their rarity in peripheral blood severely limits their adequate isolation and therapeutic use for acute ischemic stroke which necessitate their ex vivo expansion and generate early EPCs and outgrowth endothelial cells (OECs) as a result. Functional analyses of these cells, in the present study, demonstrated that only OECs endocytosed DiI-labelled acetylated low-density lipoprotein and formed tubules on matrigel, prominent endothelial cell and angiogenesis markers, respectively. Further analyses by flow cytometry demonstrated that OECs expressed specific markers for stemness (CD34), immaturity (CD133) and endothelial cells (CD31) but not for hematopoietic cells (CD45). Like BMECs, OECs established an equally tight in vitro model of human BBB with astrocytes and pericytes, suggesting their capacity to form tight junctions. Ischemic injury mimicked by concurrent deprivation of oxygen and glucose (4 hours) or deprivation of oxygen and glucose followed by reperfusion (20 hours) affected both barrier integrity and function in a similar fashion as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux, respectively. Wound scratch assays comparing the vasculoreparative capacity of cells revealed that, compared to BMECs, OECs possessed a greater proliferative and directional migratory capacity. In a triple culture model of BBB established with astrocytes, pericytes and BMEC, exogenous addition of OECs effectively repaired the damage induced on endothelial layer in serum-free conditions. Taken together, these data demonstrate that OECs may effectively home to the site of vascular injury and repair the damage to maintain (neuro)vascular homeostasis during or after a cerebral ischemic injury.

Integrates the various disciplines of the science of health disparities in one comprehensive volume The Science of Health Disparities Research is an indispensable source of up-to-date information on clinical and translational health disparities science. Building upon the advances in health disparities research over the past decade, this authoritative volume informs policies and practices addressing the diseases, disorders, and gaps in health outcomes that are more prevalent in minority populations and socially disadvantaged communities. Contributions by recognized scholars and leaders in the field—featuring contemporary research, conceptual models, and a broad range of scientific perspectives—provide an interdisciplinary approach to reducing inequalities in population health, encouraging community engagement in the research process, and promoting social justice. In-depth chapters help readers better understand the specifics of minority health and health disparities while demonstrating the importance of advancing theory, refining measurement, improving investigative methods, and diversifying scientific research. In 26 chapters, the book examines topics including the etiology of health disparities research, the determinants of population health, research ethics, and research in African American, Asians, Latino, American Indian, and other vulnerable populations. Providing a unified framework on the principles and applications of the science of health disparities research, this important volume: * Defines the field of health disparities science and suggests new directions in scholarship and research * Explains basic definitions, principles, and concepts for identifying, understanding and addressing health disparities * Provides guidance on both conducting health disparities research and translating the results * Examines how social, historical and contemporary injustices may influence the health of racial and ethnic minorities * Illustrates the increasing national and global importance of addressing health disparities * Discusses population health training, capacity-building, and the transdisciplinary tools needed to advance health equity A significant contribution to the field, The Science of Health Disparities Research is an essential resource for students and basic and clinical researchers in genetics, population genetics, and public health, health care policymakers, and epidemiologists, medical students, and clinicians, particularly those working with minority, vulnerable, or underserved populations.

Background Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. Main body In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. Conclusion Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.

Since the turn of the new millennium, ‘translational research’, the scientific process of bringing disease-targeted knowledge from the laboratory to treat patients in the clinic, has gone mainstream and is now practiced by large universities and institutes across the globe. Into this dynamic of the rapidly changing world of translational medical research this book sets the life of one of the discipline’s most influential practitioners, Anthony Cerami. His work spans more than five decades and culminated in the discovery, invention and development of diagnostics and therapeutics used daily by millions of people. Students in molecular medicine and investigators pursuing basic science in the hope of improving human health will find inspiration in examining the sacrifices and achievements of Cerami’s career in translational medicine. During his three decades at Rockefeller University his cross-disciplinary and laboratory-without-wall approach established ‘rational drug design’ as the most effective means of advancing the fields of parasitology, hematology, immunology, metabolism, therapeutics and molecular medicine. Cerami’s story and that of the evolution of translation are intimately entwined: the contours of Cerami’s career shaped by developments in translation, and in exchange, the field itself molded by Cerami’s work. To understand one is to understand the other. By examining the life of this often overlooked biochemist it is possible to intimately focus on the ideas and thought processes of a scientist who has helped to define the great acceleration in translational research over the past half century – research that, knowingly or otherwise, has most likely affected the life of almost everyone on the planet. We also gain a better understanding of the febrile creative atmosphere that percolated through the laboratories leading the way in translational medicine, and gain insight into the art, science, successes, failures and providence that underlie major scientific breakthroughs. Anybody interested in the questions of where modern medicines come from, how health outcomes around the globe are affected by research and imagination, and where the future of drug discovery is leading, will be rewarded by exploring Cerami’s life in translation. This book is not restricted to those with a professional interest in science, because anyone dedicated to living a life of creativity and discovery will be rewarded by reading this book. In many respects, Cerami’s life reflects the modern metaphor of the ‘American dream’ with his journey from humble beginnings on a chicken farm in rural New Jersey, to occupying a place in the highest echelons of the US scientific establishment. His journey in translational medicine was propelled forward by two obsessions; the idea that he could help people who were sick, and the excitement of discovery. In following his two great passions, he trained a generation of specialists in translational medicine that continue to transform our understanding of, and treatments for, human disease. Anthony Cerami’s work has shown how science has become an important force for social change by laying the foundations of modern translational medicine.