Translational Medicine Research Research Articles

Research Pioneers in Emergency Medicine—Reflections on Their Paths to Success and Advice to Aspiring Researchers: A Qualitative Study

Research in basic, translational, and clinical emergency medicine has made great strides since the formalization of emergency medicine as a specialty. Our objective is to identify and analyze strategies used by emergency medicine research pioneers to inform further advancement of research in emergency medicine, particularly for aspiring researchers and those in emerging areas, using emergency medicine medical education as one example. This was a prospective, grounded-theory, qualitative study, using a constructivist/interpretivist paradigm. Leading basic science, translational, and clinical emergency medicine researchers who completed residency before 1995 were eligible for structured interviews. Thematic coding followed an iterative process until saturation was reached. A theoretic model was developed and analyzed. Research pioneers valued advanced methodological training and mentorship. Barriers to funding were lack of recognition ofemergency medicine as a specialty, absence of a research history, and lack of training and funding resources. Deliberate interventions to improve emergency medicine research included educational sessions at national meetings, external (to emergency medicine) mentor pairings, targeted funding by emergency medicine organizations, and involvement with funding agencies. Pioneers facilitate research excellence by serving as mentors and allocating funds or protected time to develop researchers. To advance emerging subfields of research in emergency medicine, pioneers recommend advanced methodological training that is specific to the area, deliberate mentorship, and the formation of research consortia to conduct generalizable outcomes-based studies. Research pioneers in emergency medicine cite mentorship, advanced skills obtained through fellowship or graduate degrees, deliberate collaboration with experienced researchers, support from emergency medicine organizations, and forming networks as the cornerstones of success.

The current situation of intellectual property right management department in public hospitals in Shanghai and the demand analysis of medical staff in medical translation

Objective The basic feature of translational medicine is collaborative innovation by multiple disciplines. The essence of translational medicine is the management innovation. Public hospitals have the advantages of disciplines and talents, which is one of the main forces for translational medicine research. Study on the current situation of intellectual property right (IPR) management department in public hospitals and the demand analysis of medical staff in the medical translation will improve the management system of innovational medical technology and support the government policy-making. Methods Questionnaire survey was carried out in the part of Shanghai secondary and tertiary public hospitals. Results A total of 150 questionnaires were surveyed with a responding rate of 98%. Nearly 65% of inventors do not know the basic situation of the administrative staff, which is in charge of the IPR management. The main work focuses on the patent application (accounting for 70.9% of the responders). The medical staff want be supported in four areas including professional team(accounting for 62.5% of the responders), special funds(accounting for 80.3% of the responders), public research platform(accounting for 55.7% of the responders) and talent policy(accounting for 43.6% of the responders). Conclusions Full time management of IPR is proposed, active awareness of the administrative staff needs to be strengthened and government should support in these four areas. Key words: The management department of intellectual property right; Public hospitals; The demand in the progress of medical research; Medical staff

Analysis and management of the national natural science foundation of china in a special hospital

Objective To explore the management model of scientific research projects based on the application of the National Natural Science Foundation of China (NSFC). Methods We retrospectively analyzed the NSFC funding of our hospital during 2009-2017. Results Our hospital sets up the pre-experiment special project of NSFC and full-time policy, development translational medicine research center platform, introduce and train scientific talents, strength the delicacy management of scientific research and so on. Through the above measurements, NSFC funding in our hospital was significantly improved. The number of projects approved increased from 1 to 23, and the amount approved increased from 300 thousand to 21 million 350 thousand yuan during the eight yesrs. Conclusions The policy, platform, personnel and delicacy management have effectively improved the quality and quantity of NSFC, and promote the sustainable development of the hospital science and technology. Key words: National Natural Science Foundation of China; Project application; Project management; Hospital; Scientific research

New advances in translational medicine research in the field of tumor

New advances in translational medicine research in the field of tumor

Progress of fish collagen as novel biomedical material

To review the lately new progress of fish collagen as biomedical materials, and then analyze feasibility and risk management of its application as a substitute of collagen originated from mammals in clinical practice. Based on extensive research on new application and investigation of fish collagen, the paper was prepared to bring comprehensive analysis of its research and application status, and then several key points were focused on. Fish collagen has been proved to be a novel collagen of rich source, low risk of virus transmission, low biological risk, less religious barrier, and high biocompatibility. Fish collagen has promising prospect when applied in clinical practice as novel collagen especially as a substitute of collagen derived from mammals. However, very few related translational medicine research of fish collagen has been reported up to now in China. As a novel potential substitute of collagen source derived from mammals, fish collagen is concerned to be clinical feasible and necessary in translational medicine. However, massive applied basic researches should be focused on in the further investigations.

Computational Modelling of Liver Metabolism and its Applications in Research and the Clinics.

Computational models of liver metabolism are gaining an increasing importance within the research community. Moreover, their first clinical applications have been reported in recent years in the context of personalised and systems medicine. Herein, we survey selected experimental models together with the computational modelling approaches that are used to describe the metabolic processes of the liver in silico. We also review the recent developments in the large-scale hepatic computational models where we focus on object-oriented models as a part of our research. The object-oriented modelling approach is beneficial in efforts to describe the interactions between the tissues, such as how metabolism of the liver interacts with metabolism of other tissues via blood. Importantly, this modelling approach can account as well for transcriptional and post-translational regulation of metabolic reactions which is a difficult task to achieve. The current and potential clinical applications of large-scale hepatic models are also discussed. We conclude with the future perspectives within the systems and translational medicine research community.

Late Breaking Abstracts.

Late Breaking Abstracts.

New progression and direction of translational medicine on colorectal cancer

Translational medicine is characterized by its close association with precision medicine in the field of colo-rectal cancer. In particular, the studies of life histology promote the prevention and treatment of colorectal cancer entered the stage of precision medicine. Accurate molecular typing of colo-rectal cancer has been used to guide clinical practice is an important breakthrough in the field of colorectal cancer translational medicine in recent years, and its clinical value has been verified. As an important tool for the effective integration of clinical data and life histology data, the biomedical big data platform is expected to contribute to the continued breakthrough of translational medicine in precision molecular typing. New treatment methods, such as liquid biopsy technology with non-invasive, flexible features can be dynamically detected as soon as possible to find the state of somatic mutations. Among them, circulating tumor DNA has a good detection sensitivity and specificity, highlighting the value of early recurrence monitoring. In addition, new therapeutic strategies, such as immunological checkpoints and chimeric antigen receptor genetically modified T-cell therapy, are under intense study in the field of colorectal cancer. Based on the biomedical big data analysis in the context of the precise molecular typing, dynamic liquid biopsy monitoring technology, new immunotherapy and other fields will be the future of colorectal cancer translational medicine research hot and breakthrough direction. Key words: Colorectal neoplasms; Translational medicine; Precision medicine; Mole-cular subtyping; Big data; Liquid biopsy technology; Immunologic therapy

Biological and mechanical interplay at the Macro- and Microscales Modulates the Cell-Niche Fate

Tissue development, regeneration, or de-novo tissue engineering in-vitro, are based on reciprocal cell-niche interactions. Early tissue formation mechanisms, however, remain largely unknown given complex in-vivo multifactoriality, and limited tools to effectively characterize and correlate specific micro-scaled bio-mechanical interplay. We developed a unique model system, based on decellularized porcine cardiac extracellular matrices (pcECMs)—as representative natural soft-tissue biomaterial—to study a spectrum of common cell–niche interactions. Model monocultures and 1:1 co-cultures on the pcECM of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) were mechano-biologically characterized using macro- (Instron), and micro- (AFM) mechanical testing, histology, SEM and molecular biology aspects using RT-PCR arrays. The obtained data was analyzed using developed statistics, principal component and gene-set analyses tools. Our results indicated biomechanical cell-type dependency, bi-modal elasticity distributions at the micron cell-ECM interaction level, and corresponding differing gene expression profiles. We further show that hMSCs remodel the ECM, HUVECs enable ECM tissue-specific recognition, and their co-cultures synergistically contribute to tissue integration—mimicking conserved developmental pathways. We also suggest novel quantifiable measures as indicators of tissue assembly and integration. This work may benefit basic and translational research in materials science, developmental biology, tissue engineering, regenerative medicine and cancer biomechanics.

A high-performance polydimethylsiloxane electrospun membrane for cell culture in lab-on-a-chip.

Thin porous membranes are important components in a microfluidic device, serving as separators, filters, and scaffolds for cell culture. However, the fabrication and the integration of these membranes possess many challenges, which restrict their widespread applications. This paper reports a facile technique to fabricate robust membrane-embedded microfluidic devices. We integrated an electrospun membrane into a polydimethylsiloxane (PDMS) device using the simple plasma-activated bonding technique. To increase the flexibility of the membrane and to address the leakage problem, the electrospun membrane was fabricated with the highest weight ratio of PDMS to polymethylmethacrylate (i.e., 6:1 w/w). The membrane-integrated microfluidic device could withstand a flow rate of up to 50 μl/min. As a proof of concept, we demonstrated that such a compartmentalized microfluidic platform could be successfully used for cell culture with the capability of providing a more realistic in vivo-like condition. Human lung cancer epithelial cells (A549) were seeded on the membrane from the top microchannel, while the continuous flow of the culture medium through the bottom microchannel provided a shear-free cell culture condition. The tortuous micro-/nanofibers of the membrane immobilized the cells within the hydrophobic micropores and with no need of extracellular matrix for cell adhesion and cell growth. The hydrophobic surface conditions of the membrane were suitable for anchorage-independent cell types. To further extend the application of the device, we qualitatively showed that rinsing the membrane with ethanol prior to cell seeding could temporarily render the membrane hydrophilic and the platform could also be used for anchorage-dependent cells. Due to the three-dimensional (3D) topography of the membranes, three different configurations were observed, including individual single cells, monolayer cells, and 3D cell clusters. This cost-effective and robust compartmentalized microfluidic device may open up new avenues in translational medicine and pharmacodynamics research.

Engaging Latina breast cancer survivors in research: building a social network research registry.

Disparities persist in breast cancer outcomes between Latina survivors and non-Hispanic Whites. Identifying methods to ensure that Latinas participate in and benefit from translational behavioral medicine research is important to reduce disparities. We developed a "Social Network Research Registry" to enhance Latina survivors' engagement in research and explored the social networks and research/cancer organization participation in this population. We initially recruited 30 Latina breast cancer survivors ("seeds") from community organizations and identified other survivors through snowball sampling. Guided by Social Network Analysis, we assessed the structural (e.g., size) and functional (e.g., social support) characteristics of the network, willingness to join the registry, prior research participation, involvement in cancer organizations, and interest in different types of research and roles in research. The resulting network size was 98, including 53 women who enrolled in the study and 45 who were listed in the network but did not enroll. All enrolled participants (N = 53) agreed to be part of the registry. We identified 15 participants who occupied strategic positions as hubs and/or bridges. Women who were currently involved in cancer organizations were more likely to have participated in research (70.3% vs. 18.8%); χ2 (1, 53) = 11.97, p = .001. Most were interested in surveys/interviews (98%), behavioral interventions (96%), and becoming health promoters (79%). The Social Network Research Registry is an acceptable and feasible strategy to engage underrepresented Latina survivors in research. Social network analysis can be useful to identify members who occupy key positions to enhance recruitment and translational efforts.

The translational medicine of animal model for intracerebral hemorrhage

This review made a summary on animal models currently used and relative research data of intracerebral hemorrhage (ICH) translational medicine research. In this paper, comprehensive evaluation for the current research on ICH animal model, discuss the advantages and disadvantages of the current animal models of ICH in the research work. To explore the pathogenesis of cerebral hemorrhage animal model to provide the research limitations, how to improve the experimental methods, and promote the transformation of clinical medical research. Aims to provide a more precise ICH animal models for brain protection treatment research, and reasonably select ICH animal model and improve the correlation of animal experiments and clinical research. Summarized and prospected the development of ICH animal experimentation on the current and the future. Key words: Intracranial hemorrhage; Model, animal; Translational medicine

From Tissue Engineering to Regenerative Surgery

From Tissue Engineering to Regenerative Surgery

Introduction to the Special Issue on Clinical and Public Health Genomics: Opportunities for translational behavioral medicine research, practice, and policy.

Introduction to the Special Issue on Clinical and Public Health Genomics: Opportunities for translational behavioral medicine research, practice, and policy.

How Translational Medicine Is Progressively Redefining Healthcare: From Bench to Bedside, the Patient Is the Bedrock of Translational Research

Translational medicine or translation research is an umbrella term that covers specific research in biological sciences whose main goal is to increase human life expectancy by keeping us healthy (from better ideas to better health). It’s synonymous with translational medical science, disease-targeted research, or evidence-based research. Translation research is particular because of its bidirectional nature. It’s commonly called the B2B approach or bench to bedside approach because it incorporates clinical skills and observations as well as scientific hypotheses utilized by researchers in the laboratories. The whole concept functions in a loop: bench to bedside and back. It translates knowledge, skills, or science from one place to another not only by focusing on the traditional 4P-Medicine – personalization, prevention, prediction, and participation – but also by taking into consideration another 3 Ps: providing (staff training), preemptive (research and development), and point of care (making sure that healthcare can be given anytime anywhere). Because of that, translational medicine can be viewed as a paradigm shift. This revolutionary concept shows how research discoveries can translate into effective therapies… Moreover, the understanding of disease pathology and preclinical models (their availability, their relevance to the disease and their translatability are considered key focus of modern translation research or translational medicine. Disease pathology may differ from one individual to the next. Researchers in the biological and the medical fields understand that. Thus, today, pharmacogenomics or personalized medicine is a field in the making and is set to revolutionized how patients are treated because the one size fits all approach is becoming more and more a thing of the past. Disease pathology also prompts researchers to consider our genetic makeups or our DNA first thing when trying to invent drugs or medical techniques likely to improve or enhance life expectancy.

Investigations on effects of the hole size to fix electrodes and interconnection lines in polydimethylsiloxane

Translational research in bioelectronics medicine and neural implants often relies on established material assemblies made of silicone rubber (polydimethylsiloxane-PDMS) and precious metals. Longevity of the compound is of utmost importance for implantable devices in therapeutic and rehabilitation applications. Therefore, secure mechanical fixation can be used in addition to chemical bonding mechanisms to interlock PDMS substrate and insulation layers with metal sheets for interconnection lines and electrodes. One of the best ways to fix metal lines and electrodes in PDMS is to design holes in electrode rims to allow for direct interconnection between top to bottom layer silicone. Hence, the best layouts and sizes of holes (up to 6) which provide sufficient stability against lateral and vertical forces have been investigated with a variety of numbers of hole in line electrodes, which are simulated and fabricated with different layouts, sizes and materials. Best stability was obtained with radii of 100, 72 and 62 µm, respectively, and a single central hole in aluminum, platinum and MP35N foil line electrodes of 400 × 500 µm2 size and of thickness 20 µm. The study showed that the best hole size which provides line electrode immobility (of thickness less than 30 µm) within a central hole is proportional to reverse value of Young’s Modulus of the material used. Thus, an array of line electrodes was designed and fabricated to study this effect. Experimental results were compared with simulation data. Subsequently, an approximation curve was generated as design rule to propose the best radius to fix line electrodes according to the material thickness between 10 and 200 µm using PDMS as substrate material.

Long-Term Room Temperature Storage of Dry Ribonucleic Acid for Use in RNA-Seq Analysis.

RNA is an essential biological material for research in genomics and translational medicine. As such, its storage for biobanking is an important field of study. Traditionally, long-term storage in the cold (generally freezers or liquid nitrogen) is used to maintain high-quality (in terms of quantity and integrity) RNA. Room temperature (RT) preservation provides an alternative to the cold, which is plagued by serious problems (mainly cost and safety), for RNA long-term storage. In this study, we evaluated the performance of several RT storage procedures, including the RNAshell® from Imagene, where the RNA is dried and kept protected from the atmosphere, and the vacuum drying of RNA with additives such as the Imagene stabilization solution and a home-made trehalose solution. This evaluation was performed through accelerated (equivalent to 10 years for RNAshell) aging and real-time studies (4 years). To check RNA quality and integrity, we used RNA integrity number values and RNA-seq. Our study shows that isolation from atmosphere offers a superior protective effect for RNA storage compared with vacuum drying alone, and demonstrates that RNAshell permits satisfactory RNA quality for long-term RT storage. Thus, the RNA quality could meet the demand of downstream applications such as RNA-seq.

Predoctoral and Postdoctoral Training Pipeline in Translational Biomaterials Research and Regenerative Medicine.

The translation of biomaterial based and regenerative therapies from the laboratory to patients involves multiple challenges. One of the most pressing challenges is the educational one: to train a cohort of scientists and engineers capable of translating their discoveries from bench to market to clinic. To meet this need, translational training programs are being implemented globally at universities and as partnerships between universities and corporations. In this perspective, we describe two translational NIH T32 graduate and postgraduate training programs that augment the traditional approach to training early stage scientists and engineers. At the graduate level, Boston University developed and implemented the Translational Research in Biomaterials (TRB) predoctoral training program. At the postgraduate level, Rutgers, The State University of New Jersey, developed and implemented the Translational Research in Regenerative Medicine (TRRM) program for postdoctoral training. These programs are motivated by the need for training in translational research in the biomedical field, by young scientists' requests for such training, and by the fundamental challenges facing future discovery and clinical implementation of biomaterial-based technologies. The TRB program immerses trainees in the concept of translating an idea from the research laboratory to the clinic, introduces them to the challenges of such an endeavor, provides discussions with relevant faculty (for example, with businesses, patient care, or clinical trial experience), and educates them in the critical areas required for their future careers. Similarly, the TRRM program emphasizes translational research and the concept of "training without borders," which enables collaborations across several geographically dispersed institutions so as to make regional experts accessible regardless of where they are located physically. Both programs promote interdisciplinary research, expose young scientists and engineers to challenges outside of their specialty, and build interpersonal skills for cross-disciplinary communication. The TRB program focuses on quantitative science and engineering courses, together with translation-based courses in clinical trials and business. The TRRM program focuses on broadening the horizon of its trainees through exposure to a wider network of mentors than traditional postdoctoral programs, and by encouraging trainees to engage in collaborative research across at least two different laboratories. Both programs meet significant public health needs: the skills that trainees acquire are essential in future biomedical careers as they join teams that combine diverse backgrounds to meet a common goal in research, development, and ultimately commercialization.

LipidHunter Identifies Phospholipids by High-Throughput Processing of LC-MS and Shotgun Lipidomics Datasets.

Lipids are dynamic constituents of biological systems, rapidly responding to any changes in physiological conditions. Thus, there is a large interest in lipid-derived markers for diagnostic and prognostic applications, especially in translational and systems medicine research. As lipid identification remains a bottleneck of modern untargeted lipidomics, we developed LipidHunter, a new open source software for the high-throughput identification of phospholipids in data acquired by LC-MS and shotgun experiments. LipidHunter resembles a workflow of manual spectra annotation. Lipid identification is based on MS/MS data analysis in accordance with defined fragmentation rules for each phospholipid (PL) class. The software tool matches product and neutral loss signals obtained by collision-induced dissociation to a user-defined white list of fatty acid residues and PL class-specific fragments. The identified signals are tested against elemental composition and bulk identification provided via LIPID MAPS search. Furthermore, LipidHunter provides information-rich tabular and graphical reports allowing to trace back key identification steps and perform data quality control. Thereby, 202 discrete lipid species were identified in lipid extracts from rat primary cardiomyocytes treated with a peroxynitrite donor. Their relative quantification allowed the monitoring of dynamic reconfiguration of the cellular lipidome in response to mild nitroxidative stress. LipidHunter is available free for download at https://bitbucket.org/SysMedOs/lipidhunter .

"Translational Research in Medicine: Reverse the Process and Support it for Success"

"Translational Research in Medicine: Reverse the Process and Support it for Success"