Translational research and innovation in modern transplant practice:Paradigms from Greece and around the world

The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.

Translational bioengineering strategies for peripheral nerve regeneration:opportunities,challenges,and novel concepts

Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.

Novel translational strategies in colorectal cancer research

Defining translational research is still a complex task. In oncology, translational research implies using our basic knowledge learnt from in vitro and in vivo experiments to directly improve diagnostic tools and therapeutic approaches in cancer patients. Moreover, the better understanding of human cancer and its use to design more reliable tumor models and more accurate experimental systems also has to be considered a good example of translational research. The identification and characterization of new molecular markers and the discovery of novel targeted therapies are two main goals in colorectal cancer translational research. However, the straightforward translation of basic research findings, specifically into colorectal cancer treatment and vice versa is still underway. In the present paper, a summarized view of some of the new available approaches on colorectal cancer translational research is provided. Pros and cons are discussed for every approach exposed.

The 8th National Gastric Cancer Academic Conference: focus on specification, translational research, and plan

The 8th National Gastric Cancer Academic Conference, organized by Gastric Cancer Association of Chinese Anti- cancer Association and co-hosted by Beijing Cancer Hospital, Chinese Journal of Cancer Research （CJCR）, Translational Gastrointestinal Cancer （TGC）, Chinese Journal of Gastrointestinal Surgery, and Chinese Journal of Practical Surgery, was held at Beijing International Convention Center from June 15 to 16, 2013. Prof. Dr. Jiafu Ji, MD, FACS, the president of Gastric Cancer Committee, Chinese Anti-Cancer Association （CACA） and Editor-in-Chief of TGC, was the chairman of the conference （Figure 1）. Prof. Dr. Yan Sun, MD, academician of Chinese Academy of Engineering （CAE）, was the honorary chairman of the

Patient-centered developments in colon-and rectal cancer with a multidisciplinary international team:From translational research to national guidelines

Rarely,scientific developments centered around the patient as a whole arepublished.Our multidisciplinary group,headed by gastrointestinal surgeons,applied this research philosophy considering the most important aspects of thediseases“colon-and rectal cancer”in the long-term developments.Good expertcooperation/knowledge at the Comprehensive Cancer Center Ulm(CCCU)wereapplied in several phase III trials for multimodal treatments of primary tumors(MMT)and metastatic diseases(involving nearly 2000 patients and 64 centers),fortreatment individualization of MMT and of metastatic disease,for psychooncology/quality of life involving the patients’wishes,and for disease prevention.Most of the targets initially were heavily rejected/discussed in thescientific communities,but now have become standards in treatments andnational guidelines or are topics in modern translational research protocolsinvolving molecular biology for e.g.,“patient centered individualized treatment”.In this context we also describe the paths we had to tread in order to realize ournew goals,which at the end were highly beneficial for the patients from manypoints of view.This description is also important for students and youngresearchers who,with an actual view on our recent developments,might want toknow how medical progress was achieved.

Translational research in early neuroscience careers of high school students

Essentially, the knowledge of science alone offers little utility. With-out the ability to investigate, apply and communicate, science serves no purpose. That is not to undermine the importance of scientific knowledge, but there currently exists a major flaw in our high school educational system that inhibits meaningful learning experiences for most students. Application of science in local high schools is largely directed at improving performance on multiple-choice exams. Standardized tests taken by high school students are slowly progressing,

CONFERENCE At-A-Glance SOCIETY FOR ACUPUNCTURE RESEARCH“Translational Research in Acupuncture:Bridging Science,Practice and Community” Chapel Hill,NC,March 19-21,2010

THURSDAY,March 18 Pre-Conference Workshops"lntroduction to current issues in acupunclure research""ConsideratiOns for developing COllaboration research between AOM COlleges and conventionaI medicalinstitutions"

A “Stem Cells in Cancer” special issue in Translational Cancer Research

Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.

A Critique of Eye-Tracking Approach in Translation Process Research

With the rapid growth of eye-tracking studies in translation process research, concomitant methodologicalproblems have become increasingly prominent. This paper starts with the discussion of the controversial “eye-mindassumption”, and then focuses on various threats to experimental validity in research design and problems witheye-tracking data filtering and analysis. It is hoped that this discussion would be beneficial to those who are now orwill be engaged in eye-tracking based translation studies.

Research on Translation about Movie Subtitle from Relevance Theory——Take Forrest Gump for Example

With China's accession to the WTO and the integration of the global economy, the world is getting smaller and smaller. Translation on film and television drama subtitles plays a key role for cultural exchange. However, the quality of film and television translation is uneven, and the exploration of film and television translation is imperative.Subtitle translation is a special type of language conversion. From the theory of relevance, this paper analyzes the film Forrest Gump as a case, and sums up some feasible subtitle translation strategies. This paper aims at using reasonable theory to guide the translation of film subtitles, and improving the quality of translation.This article is composed of five parts, the first part is mainly introducing. The second part is an introduction to the theory of relevance. The third part is the subtitles translation of Forrest Gump. The fourth part is about the translation of film subtitles from the theory of relevance. The fifth part is a summary.

A comprehensive review of 3D cancer models for drug screening and translational research

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research.In addition to cancer cells,a range of other factors include the stroma,density and composition of extracellular matrix,cancer-associated immune cells(e.g.,cancer-associated fibroblasts cancer cell-stroma interactions and subsequent interactions,and a number of other factors(e.g.,tumor vasculature and tumor-like microenvironment in vivo)has been widely ignored in the 2D concept of culture.Despite this knowledge,the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials.This review discusses the immense importance of tumor microenvironment(TME)recapitulation in cancer research,prioritizing the individual roles of TME elements in cancer histopathology.The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement,components,and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials,some of which are discussed here.Furthermore,it discusses models for the co-assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors.Furthermore,this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.

Animal modeling in bone research—Should we follow the White Rabbit?

Animal models are live subjects applied to translational research.They provide insights into human diseases and enhance biomedical knowledge.Livestock development has favored the pace of human social development over millennia.Today's society is more aware of animal welfare than past generations.The general public has marked objections to animal research and many species are falling into disuse.The search for an ideal methodology to replace animal use is on,but animal modeling still holds great importance to human health.Bone research,in particular,has unmet requirements that in vitro technologies cannot fully address.Standardizing novel models remains necessary and rabbits are gaining in popularity as potential bone models.Our aim here is to provide a broad overview of animal modeling and its ethical implications,followed by a narrower focus on bone research and the role rabbits are playing in the current scenario.

Magnetic Resonance Imaging Studies of Neurodegenerative Disease:From Methods to Translational Research

Neurodegenerative diseases(NDs)have become a significant threat to an aging human society.Numerous studies have been conducted in the past decades to clarify their pathologic mechanisms and search for reliable biomarkers.Magnetic resonance imaging(MRI)is a powerful tool for investigating structural and functional brain alterations in NDs.With the advantages of being non-invasive and non-radioactive,it has been frequently used in both animal research and large-scale clinical investigations.MRI may serve as a bridge connecting micro-and macro-level analysis and promoting bench-to-bed translational research.Nevertheless,due to the abundance and complexity of MRI techniques,exploiting their potential is not always straightforward.This review aims to briefly introduce research progress in clinical imaging studies and discuss possible strategies for applying MRI in translational ND research.

The generation and use of animal models of osteosarcoma in cancer research

Osteosarcoma is the most common malignant bone tumor affecting children and adolescents.Currently,the most common treatment is surgery combined with neoadjuvant chemotherapy.Although the survival rate of patients with osteosarcoma has improved in recent years,it remains poor when the tumor(s)progress and distant metastases develop.Therefore,better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers,as well as targeted therapies for both primary and metastatic osteosarcoma.The present review described animal models currently being used in research investigating osteosarcoma,and their characteristics,advantages,and disadvantages.These models may help elucidate the pathogenic mechanism(s)of osteosarcoma and provide evidence to support and develop clinical treatment strategies.

Translational research and its effects on medicine in China

Translational research has become a globally recognized model of medical research. Chinese government and doctors have begun to discuss the plan for its development. But most articles are focusing on the advantages rather than its pros and cons. In this essay, the authors discuss the disadvantages of translational research, its effects on clinical work and medical education, highlighting some potential problems and risks in theory and practice on case basis. Some important research management requirements are summarized in this essay to help bring the therapy from the research laboratory to the patient＇s bedside.

Status of precision medicine approaches to traumatic brain injury

Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.

Global progress against cancer—challenges and opportunities

The last ten years have seen remarkable progress in cancer research. However, despite significant breakthroughs in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Cancer＇s complexity compounded with financial, policy and regulatory roadblocks has slowed the rate of progress being made against cancer. In this paper, we review a few of the most recent breakthroughs that are fueling medical advances and bringing new hope for patients affected by this devastating disease. We also address the challenges facing us and the opportunities to accelerate future progress against cancer. The efforts of the American Association for Cancer Research （AACK） to address the cancer burden already extend beyond the borders of the United States of America. The AACR is committed to increasing its efforts to stem the tide of cancer worldwide by promoting innovative programs, strategies, and initiatives for cancer researchers and all those engaged in cancer-related biomedical sciences around the world.

The 3rd Symposium on Animal Models of Primates——The Application of Non-Human Primates to Basic Research and Translational Medicine

In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues： （1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.

Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.

New burns and trauma journal celebrating translational research

Welcome to the journal of Burns & Trauma launched in 2013 and published by the prestigious Wolters Kluwer Health. We are grateful to promote a cultural challenge toward a new horizon in the field of translational research (TR). We enjoy to work together with the common objective to perform continuous medical education programs, exploring the methods in research, designing study, and to improve multidisciplinary and multiprofessional collaboration in the basic sciences and in the clinical trials. Defined narrowly, epistemology is the study of knowledge and justified belief. Epistemology is concerned with the following questions: What are the necessary and sufficient conditions of knowledge? What are its sources? What is its structure and what are its limits? More broadly, epistemology is about issues having to do with the creation and dissemination of knowledge in particular areas of inquiry as defined and revisiting at the beginning of the last decades. Translational medicine (TM) should meet the demands to maintain or expanding the biomedical workforce and education programs that attract and retain young people in the translational and biomedical sciences. With this present contributes, we invite the members of the editorial board of Burns & Trauma to encourage submitting, in a special section, their personal experience about the philosophy of "Translation research." If this has a chance, welcome to the researchers, clinicians, and the allied people for their decisive contributions to strengthen the importance of a common way about the principles and methods of basic and clinical research. TR and TM represent a dynamic entity making a link, a sort of bridge, "from bench to bedside", or from laboratory experiments through clinical trials to point-of-care patient applications. Epistemological pluralism is a critical point for conducting innovative, collaborative research which can lead to more successful integrated and successfully study, particularly important in the field of burns and trauma.