What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society.

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.

The past, present, and future of liver cancer research in China.

Liver cancer is among the leading causes of cancer-related death worldwide and China accounts for nearly half of the global burden of liver cancer. Effective interventions such as hepatitis vaccinations, new blood tests and imaging tests significantly decreased the incidence worldwide, especially in China. Unraveling the systemic and molecular mechanisms of liver cancer would contribute to develop more effective therapies to prolong the 5 year survival of the patients. The Chinese funding agencies have been paying high attention to the basic and translational research of liver cancer. Over the last decade, the National Natural Science Foundation of China (NSFC) initiated a panel of research programs which supported liver cancer research in multiple directions. Besides, great progress has been made in basic and clinical research, platform construction and drug development in the field of liver cancer. In this article, we summarized the funding landscape, research progress, cooperation among countries and institutions, and drug discovery in China, with an attempt to compare the status and outcome with our peers globally.

Universities' Scientific and Technological Transformation in China: Its Efficiency and Influencing Factors in the Yangtze River Economic Belt.

Universities are important sources of knowledge and key members of the regional innovation system. The key problem in Chinese universities is the low efficiency of the scientific and technological (S&T) transformation, which limits the promotion of regional innovation and economic development. This article proposes the three-stage efficiency analytical framework, which regards it as a complex and interactive process. Avoiding the problem of considering the input and output of university S&T transformation as a "black box" and neglecting the links among different transformation stages. The super efficiency network SBM model is applied to the heterogeneous region of the Yangtze River Economic Belt. Empirical research proves that university S&T transformation has not been effectively improved and the scientific resources invested in universities have not been efficiently utilized in recent years. Generally, Despite the correlation between regional economy and transformation efficiency, the exclusive increase in resources is not enough. Regional openness and the quality of research talents are key factors for the application of technological innovation and technology marketization. Universities should not only pursue the number of research outputs but pay more attention to high-quality knowledge production to overcome difficulties in research achievements transformation.

Cancer stem cells: advances in biology and clinical translation-a Keystone Symposia report.

The test for the cancer stem cell (CSC) hypothesis is to find a target expressed on all, and only CSCs in a patient tumor, then eliminate all cells with that target that eliminates the cancer. That test has not yet been achieved, but CSC diagnostics and targets found on CSCs and some other cells have resulted in a few clinically relevant therapies. However, it has become apparent that eliminating the subset of tumor cells characterized by self-renewal properties is essential for long-term tumor control. CSCs are able to regenerate and initiate tumor growth, recapitulating the heterogeneity present in the tumor before treatment. As great progress has been made in identifying and elucidating the biology of CSCs as well as their interactions with the tumor microenvironment, the time seems ripe for novel therapeutic strategies that target CSCs to find clinical applicability. On May 19-21, 2021, researchers in cancer stem cells met virtually for the Keystone eSymposium "Cancer Stem Cells: Advances in Biology and Clinical Translation" to discuss recent advances in the understanding of CSCs as well as clinical efforts to target these populations.

Special Issue "Microglia Heterogeneity and Its Relevance for Translational Research".

Microglia are necessary for the development and function of the central nervous system (CNS) [...].

Basic and Translational Research in Cardiac Repair and Regeneration: JACC State-of-the-Art Review.

This paper aims to provide an important update on the recent preclinical and clinical trials using cell therapy strategies and engineered heart tissues for the treatment of postinfarction left ventricular remodeling and heart failure. In addition to the authors' own works and opinions on the roadblocks of the field, they discuss novel approaches for cardiac remuscularization via the activation of proliferative mechanisms in resident cardiomyocytes or direct reprogramming of somatic cells into cardiomyocytes. This paper's main mindset is to present current and future strategies in light of their implications for the design of future patient trials with the ultimate objective of facilitating the translation of discoveries in regenerative myocardial therapies to the clinic.

Emerging technologies and infection models in cellular microbiology.

The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health.

Microbiota in Health and Disease-Potential Clinical Applications.

Within the last two decades tremendous efforts in biomedicine have been undertaken to understand the interplay of commensal bacteria living in and on our human body with our own human physiology. It became clear that (1) a high diversity especially of the microbial communities in the gut are important to preserve health and that (2) certain bacteria via nutrition-microbe-host metabolic axes are beneficially affecting various functions of the host, including metabolic control, energy balance and immune function. While a large set of evidence indicate a special role for small chain fatty acids (SCFA) in that context, recently also metabolites of amino acids (e.g., tryptophan and arginine) moved into scientific attention. Of interest, microbiome alterations are not only important in nutrition associated diseases like obesity and diabetes, but also in many chronic inflammatory, oncological and neurological abnormalities. From a clinician's point of view, it should be mentioned, that the microbiome is not only interesting to develop novel therapies, but also as a modifiable factor to improve efficiency of modern pharmaceutics, e.g., immune-therapeutics in oncology. However, so far, most data rely on animal experiments or human association studies, whereas controlled clinical intervention studies are spare. Hence, the translation of the knowledge of the last decades into clinical routine will be the challenge of microbiome based biomedical research for the next years. This review aims to provide examples for future clinical applications in various entities and to suggest bacterial species and/or microbial effector molecules as potential targets for intervention studies.

A decade retrospective of medical robotics research from 2010 to 2020.

Robotics is a forward-looking discipline. Attention is focused on identifying the next grand challenges. In an applied field such as medical robotics, however, it is important to plan the future based on a clear understanding of what the research community has recently accomplished and where this work stands with respect to clinical needs and commercialization. This Review article identifies and analyzes the eight key research themes in medical robotics over the past decade. These thematic areas were identified using search criteria that identified the most highly cited papers of the decade. Our goal for this Review article is to provide an accessible way for readers to quickly appreciate some of the most exciting accomplishments in medical robotics over the past decade; for this reason, we have focused only on a small number of seminal papers in each thematic area. We hope that this article serves to foster an entrepreneurial spirit in researchers to reduce the widening gap between research and translation.

CRISPR-derived genome editing therapies: Progress from bench to bedside.

The development of CRISPR-derived genome editing technologies has enabled the precise manipulation of DNA sequences within the human genome. In this review, we discuss the initial development and cellular mechanism of action of CRISPR nucleases and DNA base editors. We then describe factors that must be taken into consideration when developing these tools into therapeutic agents, including the potential for unintended and off-target edits when using these genome editing tools, and methods to characterize these types of edits. We finish by considering specific challenges associated with bringing a CRISPR-based therapy to the clinic, including manufacturing, regulatory oversight, and considerations for clinical trials that involve genome editing agents.

New insights into the microbiota of wild mice.

Laboratory mice have long been an invaluable tool in biomedical science and have made significant contributions in research into life-threatening diseases. However, the translation of research results from mice to humans often proves difficult due to the incomplete nature of laboratory animal-based research. Hence, there is increasing demand for complementary methods or alternatives to laboratory mice that can better mimic human physiological traits and potentially bridge the translational research gap. Under these circumstances, the natural/naturalized mice including "wild", "dirty", "wildling", and "wilded" systems have been found to better reflect some aspects of human pathophysiology. Here, we discuss the pros and cons of the laboratory mouse system and contemplate how wild mice and wild microbiota are able to help in refining such systems to better mimic the real-world situation and contribute to more productive translational research.

Reimagining the peer-review system for translational health science journals.

Retractions of coronavirus disease 2019 (COVID-19) papers in high impact journals, such as The Lancet and the New England Journal of Medicine, have been panned as major scientific fraud in public media. The initial reaction to this news was to seek out scapegoats and blame individual authors, peer-reviewers, editors, and journals for wrong doing. This paper suggests that scapegoating a few individuals for faulty science is a myopic approach to the more profound problem with peer-review. Peer-review in its current limited form cannot be expected to adequately address the scope and complexity of large interdisciplinary science research collaboration, which is central in translational research. In addition, empirical studies on the effectiveness of traditional peer-review reveal its very real potential for bias and groupthink; as such, expectations regarding the capacity and effectiveness of the current peer review process are unrealistic. This paper proposes a new vision of peer-review in translational science that, on the one hand, would allow for early release of a manuscript to ensure expediency, whereas also creating a forum or a collective of various experts to actively comment, scrutinize, and even build on the research under review. The aim would be to not only generate open discussion and oversight respecting the quality and limitations of the research, but also to assess the extent and the means for that knowledge to translate into social benefit.

The evolving landscape of untargeted metabolomics.

AIMS: Untargeted Metabolomics is a "hypothesis-generating discovery strategy" that compares groups of samples (e.g., cases vs controls); identifies the metabolome and establishes (early signs of) perturbations. Targeted Metabolomics helped gather key information in life sciences and disclosed novel strategies for the treatment of major clinical entities (e.g., malignancy, cardiovascular diabetes mellitus, drug toxicity). Because of its relevance in biomarker discovery, attention is now devoted to improving the translational potential of untargeted Metabolomics. DATA SYNTHESIS: Expertise in laboratory medicine and in bioinformatics helps solve challenges/pitfalls that may bias metabolite profiling in untargeted Metabolomics. Clinical validation (availability/reliability of analytical instruments) and profitability (how many people will use the test) are mandatory steps for potential biomarkers. Biomarkers to predict individual patient response, patient populations that will best respond to specific strategies and/or approaches for an optimal response to treatment are now being developed. Additional help is expected from professional, and regulatory Agencies as to guidelines for study design and data acquisition and analysis, to be applied from the very beginning of a project. Evidence from food, plant, human, environmental, and animal research argues for the need of miniaturized approaches that employ low-cost, easy to use, mobile devices. ELISA kits with such characteristics that employ targeted metabolites are already available. CONCLUSIONS: Improving knowledge of the mechanisms behind the disease status (pathophysiology) will help untargeted Metabolomics gather a direct positive impact on welfare and industrial advancements, and fade uncertainties perceived by regulators/payers and patients concerning variables related to miniaturised instruments and user-friendly software and databases.