Biomedical Research Support Research Articles

One-step generation of droplet-filled hydrogel microfibers for 3D cell culture using an all-aqueous microfluidic system

Hydrogel microfibers, which are characterized by flexible mechanical properties, a uniform spatial distribution, large surface areas, and excellent biocompatibility, hold great potential for various biomedical applications. However, the fabrication of heterogeneous hydrogel microfibers with high cell-loading capacity and the ability to carry multiple components via an environmentally friendly method remains challenging. In this study, we developed a novel pneumatic pump-assisted all-aqueous microfluidic system that enables the one-step fabrication of all-aqueous droplet-filled hydrogel microfibers with unique morphologies and adjustable configurations. By designing a pump-valve cycling system and selecting two immiscible fluids with stable water interfaces (dextran and polyethylene glycol), we successfully fabricated alginate microfibers with equidistantly arranged droplets through the ionotropic gelation reaction between sodium alginate and calcium chloride. The droplet size, interdroplet spacing, and microfiber dimensions could be flexibly controlled by adjusting the flow rates of the inner-phase, middle-phase, and outer-phase inlets. The results showed that the system enabled the high-throughput in situ formation of functional three-dimensional cell spheroids. The generated cell spheroids exhibited excellent cell viability and drug-testing functionality, indicating their potential applications in cell cultures. The developed technique offers strong support for future biomedical research and applications, and provides a new approach for the preparation of multifunctional hydrogel microfibers for materials science, tissue engineering, and drug testing.

The Harraseeket Conference – Revisiting systems for ethics oversight of research with human participants

The current system of ethical oversight in the United States is based on Institutional Review Board (IRB) review. The system was established in response to well-known and egregious mistreatment of subjects in both biomedical and social and behavioral research. In the decades since the research regulations were enacted, reaction to the burden of IRB oversight has led the system to focus on compliance and limit its active oversight disproportionately to studies that could present the risk of physical harm. At the same time, the characteristics of the research enterprise have changed and methodologies now present novel risks that were not envisioned in the regulations. We convened a group of IRB professionals, academic leaders, and others to discuss limitations of the current system, how that system could be changed to recognize evolving risks and an increasing focus on participant and community voice, and how it could better serve the needs of researchers and support the societal project of science as a public good. Recommendations included a call to reexamine the academic incentive structure, to develop a system to support consideration of ethical principles from the time of study design, and to explicitly provide different ethical support and oversight for high-risk interventional trials and lower risk biomedical and social behavioral research.

Summary of fifth annual public MCBK meeting: Mobilizing computable biomedical knowledge (CBK) around the world.

The massive growth of biomedical knowledge in computable formats poses a challenge for organizations as they consider mobilizing artifacts to be findable, accessible, interoperable, reusable, and trustable. Formed in 2016, the Mobilizing Computable Biomedical Knowledge (MCBK) community is taking action to ensure that health organizations have the infrastructure in place to access and apply computable knowledge; to develop national policies and standards that require all data to be discoverable and available for safe and fair use; and to promote the widespread adoption and implementation of health knowledge in support of healthcare, biomedical research, public health, and education. This report summarizes the main outcomes of the Fifth Annual MCBK meeting, also considered the first manifestly global MCBK meeting, which was held virtually July 12 to 13, 2022. Over 200 participants from diverse domains around the world joined this meeting to frame and address important dimensions for mobilizing CBK.

An ontology for very large numbers of longitudinal health records to facilitate data mining and machine learning

Despite the extensive experience of the authors working in industry with a variety of electronic health records that worked well in their intended context, none currently available in reasonably large numbers seem to have ontologies and formats that will scale well to very large numbers of detailed cradle-to-grave longitudinal health records facilitating knowledge extraction. By that we mean data mining, Deep Learning neural nets and all related analytic and predictive methods for biomedical research and clinical decision support potentially applied to the health records of an entire nation. They are mostly far too complicated to support frequent high-dimensional analysis, which is required because such records will update (or should update) dynamically on a regular basis, will in future include new tests etc. acquired daily by translational medical research, and not least allow public health, research, and diagnostic, vaccine, and drug development teams to respond quickly to emergent epidemics like COVID-19. A Presidential Advisory team call in 2010 for interoperability and ease of data mining for medical records is discussed and the situation seems still not fully resolved. The solution appears to lie between efficient comma separated value files and the ability to embellish these with a moderate degree of more elaborate ontology. One recommendation is made here with discussion and analysis that should guide alternative and future approaches. It combines demographic, comorbidity, genomic, diagnostic, interventional, and outcomes information along with time/date stamping method appropriate to analysis, with facilities for special research studies. By using a “metadata operator”, a suitable balance between a comma separated values file and an ontological structure is possible.

Research for the Future: An Overview of the FASEB Shared Research Resources Task Force's Finding and Recommendations.

The Federation of American Societies for Experimental Biology (FASEB) is composed of 28 member societies, representing over 115,000 individual scientists, including the Association of Biomedical Research Facilities and its members. As part of FASEB's mission to advance awareness and support of biological and biomedical research, the Federation remains committed to sustaining support for the resources that investigators use to conduct rigorous research. This includes shared resources and the core facility staff that enable researchers to have widespread access to state-of-the art technologies and expertise. Recognizing the fundamental role of shared resources in driving biomedical research progress, FASEB established the Shared Research Resources Task Force in June 2020 to discuss ongoing policy challenges related to shared resources and core facilities and identify ways to enhance their recognition and sustainability within the research enterprise. In addition to publishing a report outlining its final recommendations, the Task Force hosted a Virtual Roundtable with external stakeholders to exchange ideas and best practices about strengthening shared resources and elevating team science to its full potential. Taken together, these efforts demonstrate a key initial step toward addressing long-standing challenges and advancing shared priorities.

The evolving privacy and security concerns for genomic data analysis and sharing as observed from the iDASH competition.

Concerns regarding inappropriate leakage of sensitive personal information as well as unauthorized data use are increasing with the growth of genomic data repositories. Therefore, privacy and security of genomic data have become increasingly important and need to be studied. With many proposed protection techniques, their applicability in support of biomedical research should be well understood. For this purpose, we have organized a community effort in the past 8 years through the integrating data for analysis, anonymization and sharing consortium to address this practical challenge. In this article, we summarize our experience from these competitions, report lessons learned from the events in 2020/2021 as examples, and discuss potential future research directions in this emerging field.

Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer's Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor.

Mutation A713T in the amyloid precursor protein (APP) has been linked to cases of Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA) and cerebrovascular disease. Despite its rarity, it has been observed in several families from the same geographical area, in the Calabria region in Southern Italy. Genotyping of 720,000 genome-wide SNPs with the HumanOmniExpress BeadChip was performed for six patients that were representative of apparently unrelated Calabrian families, as well as a Belgian subject of Italian descent (all with the same A713T mutation and disease). Their genomic structure and genetic relationships were analyzed. Demographic reconstruction and coalescent theory were applied to estimate the time of the most recent common ancestor (tMRCA) among patients. Results show that all A713T carriers fell into the genetic variability of Southern Italy and were not more closely related to each other than to any other healthy Calabrian individual. However, five out of seven patients shared a 1.7 Mbp-long DNA segment centered on the A713T mutation, making it possible to estimate a tMRCA for its common origin in the Calabrian region dating back over 1000 years. The analysis of affected individuals with methodologies based on human population genomics thus provides informative insights in support of clinical observations and biomedical research.

Multiscale Computational Modeling of Vascular Adaptation: A Systems Biology Approach Using Agent-Based Models.

The widespread incidence of cardiovascular diseases and associated mortality and morbidity, along with the advent of powerful computational resources, have fostered an extensive research in computational modeling of vascular pathophysiology field and promoted in-silico models as a support for biomedical research. Given the multiscale nature of biological systems, the integration of phenomena at different spatial and temporal scales has emerged to be essential in capturing mechanobiological mechanisms underlying vascular adaptation processes. In this regard, agent-based models have demonstrated to successfully embed the systems biology principles and capture the emergent behavior of cellular systems under different pathophysiological conditions. Furthermore, through their modular structure, agent-based models are suitable to be integrated with continuum-based models within a multiscale framework that can link the molecular pathways to the cell and tissue levels. This can allow improving existing therapies and/or developing new therapeutic strategies. The present review examines the multiscale computational frameworks of vascular adaptation with an emphasis on the integration of agent-based approaches with continuum models to describe vascular pathophysiology in a systems biology perspective. The state-of-the-art highlights the current gaps and limitations in the field, thus shedding light on new areas to be explored that may become the future research focus. The inclusion of molecular intracellular pathways (e.g., genomics or proteomics) within the multiscale agent-based modeling frameworks will certainly provide a great contribution to the promising personalized medicine. Efforts will be also needed to address the challenges encountered for the verification, uncertainty quantification, calibration and validation of these multiscale frameworks.

An Interview with Professor Jonathan King. Part I: on Social Responsibility and Activism in Academia

For nearly four decades, Prof. King has served as a faculty member in the Department of Biology at MIT. His work on protein folding and, importantly, misfolding as they relate to human disease and virus assembly has garnered numerous awards and honors: He was a Woodrow Wilson National Fellow, Jane Coffin Childs Fund Fellow, AAAS Fellow, Guggenheim Fellow, and recipient of the National Institutes of Health (NIH) Merit Award. Additionally, Prof. King has taken critical roles at the intersection of science and public policy, including a tenure as President of the Biophysical Society in 1999. In 2003, he received the MIT Martin Luther King Leadership Award, which recognizes individuals who “embody the spirit of Dr. King’s work” [1] in their contributions to the MIT community. Prof. King’s recent efforts have focused on championing federal support for biomedical research as well as criticizing unrestrained defense spending. In part I of this interview, we examine the connections between science, activism, and policy through the lens of Prof. King’s diverse experiences as an academic and activist.

Transition to Independent Research Funding Among National Institutes of Health K Grant Awardees at Departments of Orthopaedic Surgery.

The National Institutes of Health (NIH) supports mentored research career development awards (K awards) to increase the pipeline of independently funded scientists. This study analyzed the portfolio of K grants that were awarded to orthopaedic surgery departments and characterized the factors that were associated with successful transition to independent NIH research funding, including R01 grants. This was a retrospective cohort study of K-award recipients in orthopaedic surgery departments in the United States from 1996 to 2018. A query was performed on the NIH Research Portfolio Online Reporting Tools (RePORT) database for NIH grants that were awarded to departments of orthopaedic surgery, general surgery, otolaryngology, obstetrics and gynecology, ophthalmology, and urology. Rates of transition to independent research funding were compared by specialty for K grants that were awarded from 1996 to 2011. The percentage of faculty with mentored research career development awards and the return on investment (ROI) were calculated. An internet and Scopus (Elsevier) database search determined the investigator characteristics. The factors that were associated with successful transition to independent funding were determined via chi-square and unpaired t tests. Sixty K-award recipients were identified in orthopaedic surgery departments. Most were men (77%) and research scientists (53%). Fifty percent of the K-award recipients transitioned to independent research funding. Research scientists had the highest rate of transition to independent research funding (71%, p = 0.016) relative to clinicians (0%) and orthopaedic surgeons (40%). Higher levels of publication productivity were associated with successful transition to independent research funding. Similar rates of transition to independent research funding existed among surgical specialties (p = 0.107). Orthopaedic surgery had the lowest percentage of faculty with a K award (1.4%) but had the highest ROI (198%) of these awards. Orthopaedic surgery had similar rates of transition to independent research funding when compared with other surgical specialties but had a lower prevalence of K awards among faculty. Orthopaedic surgeon-scientists have lower rates of transition to independent research funding when compared with their research-scientist colleagues. These findings highlight a need for greater support to foster the pipeline of future NIH-funded orthopaedic investigators. As the largest support of biomedical research in the U.S., the NIH is an important stakeholder in orthopaedic innovations and discoveries. This study highlights barriers in the procurement of NIH funding across surgical specialties and affirms the need for greater resources toward supporting NIH funding in orthopaedic surgery.

Importance of scientific collaboration in contemporary drug discovery and development: a detailed network analysis

BackgroundGrowing evidence shows that scientific collaboration plays a crucial role in transformative innovation in the life sciences. For example, contemporary drug discovery and development reflects the work of teams of individuals from academic centers, the pharmaceutical industry, the regulatory science community, health care providers, and patients. However, public understanding of how collaborations between academia and industry catalyze novel target identification and first-in-class drug discovery is limited.ResultsWe perform a comprehensive network analysis on a large scientific corpus of collaboration and citations (97,688 papers with 1,862,500 citations from 170 million scientific records) to quantify the success trajectory of innovative drug development. By focusing on four types of cardiovascular drugs, we demonstrate how knowledge flows between institutions to highlight the underlying contributions of many different institutions in the development of a new drug. We highlight how such network analysis could help to increase industrial and governmental support, and improve the efficiency or accelerate decision-making in drug discovery and development.ConclusionWe demonstrate that network analysis of large public databases can identify and quantify investigator and institutional relationships in drug discovery and development. If broadly applied, this type of network analysis may help to enhance public understanding of and support for biomedical research, and could identify factors that facilitate decision-making in first-in-class drug discovery among academia, the pharmaceutical industry, and healthcare systems.

Setting and motivation in the decision to participate: An approach to the engagement of diverse samples in mobile research

Internet and mobile based research are powerful tools in the creation of large, cohort studies (eCohort). However, recent analysis indicates that an underrepresentation of minority and low income groups in these studies might exceed that found in traditional research [1–5]. In this report, we present findings from an experiment in research engagement using the Eureka Research Platform developed to enroll diverse populations in support of biomedical clinical research. This experiment involved the recruitment of African American and Latino participants in a smartphone based survey at a temporary, charitable, dental event sponsored, in part, by the research team, in order to explore the impact of setting and approach on recruitment outcomes. 211 participants enrolled including a significant representation of African Americans (51%) and Latinos (31%) and those with education levels at high school or less (37%). Interviews conducted after the study confirmed that our recruitment efforts within the context of a service event affected the decision to participate. While further research is necessary, this experiment holds promise for the engagement of underrepresented groups in research.

A 10-Year Study on the Efficacy of Biomedical Research Support Programs at a Public University

A 10-Year Study on the Efficacy of Biomedical Research Support Programs at a Public University

The journey of success: from an idea to a journal

Dear Sir,
 From the beginning of life on this planet research and writing remained one of the most important aspect for getting more attentions and values. But, with the pas- sage of times different methods has been introduced to share the knowledge and information i.e. from hand writing to hard publication and then to online publication. Dear readers, it was a story of 2015 when the honorable Dr. Phuc Van Pham (Founder and Editor-in-Chief) came with an idea and started the journal with name Biomedical Research and Therapy is the official journal of the Laboratory of Stem Cell Research and Application (SCL) (now as Stem Cell Institute, VNUHCM University of Science, Ho Chi Minh city, Viet Nam). After launching the journal, it was thinking that the journal will not exist for long time, be- cause it was a hard journey with limited resources. However, the journal is entered in to their 5th volume in 2018. Due to the hard working, creative ideas, team working and non-stoppable efforts of Dr. Pham and his team proofed that Biomedical Research and Therapy is one the emerging journal in the field of biomedical sciences. The journal is now indexed and abstracted by world renowned databases including Web of Science, Scopus, Embase, Index Copernicus, Ebsco, and Google Scholar.
 In a very short time of period the journal become more popular in the Asian countries. Researchers from different parts of the world is publishing their work in Biomedical Research and Therapy. On the behalf of Editor-in-Chief and Editorial Office of Biomedical Research and Therapy I am thankful and extended my gratitude to every single person who contributed for this journal. We also acknowledge the support of Springer International Publisher.
 I do hope that all of you will continue your valuable and non-stoppable support for Biomedical Research and Therapy.
 
 Tauseef Ahmad
 Associate Editor, Biomedical Research and Therapy

Biomedical Research Priorities for Modern Syphilis Clinical Management, Diagnosis, and Vaccines: Overview and Commentary for Unit 1.

The first session at the 2016 Syphilis Summit provided an opportunity for laboratory researchers and clinicians to comment on gaps in biomedical knowledge and technologies. Predominant themes in the presentations and discussion included the need for optimization of existing diagnostic tests, commercial availability, and Food and Drug Administration approval of nucleic acid amplification tests for primary and secondary syphilis, development of sensitive and specific new blood tests for diagnosis of active (vs treated) syphilis infection, clarification of the best measures for adequacy of response to treatment, continued study of complications of syphilis, including neurosyphilis and ocular syphilis, and development of a safe and effective vaccine that will protect against transmission and complications of disseminated infection (including congenital and neurosyphilis). Renewed and sustained support of biomedical syphilis research and an influx of talent could move the needle in the fight against this reemerging ancient disease.

The uncertain fate of the National Institutes of Health (NIH) pediatric research portfolio.

The amount of federal dollars allocated to improving the health of our pediatric population can serve as an indicator of the priority placed on child well-being. Although Congress has established novel mechanisms that marginally increase pediatric research funding, the pediatric research portfolio is facing an increasingly uncertain fate. This work examines pediatric, perinatal and pediatric research initiative (PRI) spending using data collected by the NIH that uses the novel research, condition and disease categorization system. Further, this work reports on recent policy developments in pediatric biomedical research and offers recommendations to insulate this portfolio from future uncertainty. Federal support for pediatric research has declined with average annual growth rates of NIH pediatric spending dropping from 12.8% (FY 1998-2003) to 1.7% (FY 2004-2015). After taking into account Biomedical Research and Development Price Index growth, the pediatric research portfolio's purchasing power has declined by 15.9% (FY 2004-2015). Federal support for pediatric biomedical research has plateaued in nominal terms and declined significantly in real terms. Future congressional action will be necessary to protect gains and to expand the capacity of the pediatric portfolio.

Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal research investment to accelerate the discovery of the next generation of cancer treatments. Another major trend in this year's report is progress in precision medicine approaches to treat cancer. Although precision medicine offers promise to people with cancer and their families, that promise is only as good as our ability to make these treatments available to all patients. My presidential theme, "Delivering Discoveries: Expanding the Reach of Precision Medicine," focuses on tackling this formidable challenge so that new targeted therapies are accessible to anyone who faces a cancer diagnosis. By improving access to high-quality care, harnessing big data on patient outcomes from across the globe, and pursuing innovative clinical trials, I am optimistic that we will speed the delivery of these most promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO President, 2017 to 2018.

Mitochondrial Dysfunction in Type 2 Diabetic Skeletal Muscle Cells

Type 2 diabetes (T2D) is an epidemic disease characterized by high blood glucose levels and insulin resistance and is usually associated with obesity. Inadequate glucose utilization by the cell leads to an increase in high fat utilization to make cellular energy, which can lead to mitochondrial dysfunction. Typically, autophagy maintains homeostasis by removing damaged portions of the mitochondria and recycling the functional components to form new efficient mitochondria. The main focus of this project is to analyze if there is an impairment of the autophagy process in T2D that leads to an accumulation of dysfunctional mitochondria. We also evaluated mitochondrial dynamics to determine if the rate of mitochondrial fission exceeds that of fusion, as this may also explain the accumulation. Using an in vitro model of T2D, fluorescent microscopy and biochemical analysis of cells treated with high fats were evaluated to look at mitochondrial dynamics and number. Microscopic analysis showed a decrease in mitochondrial number and a decrease in mitochondrial membrane potential in T2D cells versus control. Furthermore, results revealed that in a diabetic environment there was an increase in mitochondrial fragmentation as seen with an increase in DRP‐1 expression. Lastly, results showed that Beclin‐1 increases under diabetic conditions signifying that autophagy is still being activated. In conclusion, our results demonstrate that there is an increase in mitochondrial fission and activation of autophagy in T2D. More work is needed to determine if fission occurs at a rate faster than the normal autophagy response can handle to explain the consequences of T2D.Support or Funding InformationCalifornia State University, Los Angeles Louis Stokes Alliance for Minority Participation (CSULA‐ LSAMP)andCalifornia State University, Los Angeles Minority Opportunities in Research Programs‐ Minority Biomedical Research Support Program‐Research Initiative for Scientific Enhancement (CSULA MORE‐ RISE Undergraduate)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Internal grant review to increase grant funding for junior investigators.

Decreasing biomedical research support over the past decade has driven many talented young scientists to seek careers outside academia. In 2011, the Department of Neurology at Johns Hopkins University School of Medicine developed an internal grant review program (IGRP) to systematically review career development awards (CDAs) and research grants (e.g., R01s) for junior investigators prior to NIH submission. With IGRP implementation, we observed significant increases in the number of CDAs and R-grants awarded to junior investigators. Thus, internal grant review is an effective means for supporting junior faculty and help them retain their research roles within academia. This article is protected by copyright. All rights reserved.

Chasing cures: Rewards and risks for rare disease patient organisations involved in research

Rare disease patient organisations (RDPOs) provide funding, logistic support and ideas for biomedical research. The literature, however, largely consists of case studies of successful RDPOs, and theoretical analyses of their potential influence on biomedical science. RDPOs’ involvement is portrayed as an example of patient empowerment and democratisation of research that allows some societal groups to challenge researchers’ traditional control of research agendas. Little is known about whether this optimistic view reflects common experiences of RDPOs or how research involvement impacts on RDPOs themselves. In our mixed methods study of a broad group of Australian RDPOs, organisational leaders identified psychological and practical benefits of supporting research but, in contrast with prevailing accounts, often struggled to uphold organisational and personal interests when engaging with researchers. Leaders reported difficulty fundraising for research and allocating funds in ways likely to support the RDPOs’ goals. They had concerns about promoting ‘false hope’ and noted conflicts between researchers’ and patients’ interests. Some were disillusioned with research and frustrated by lack of opportunities for genuine involvement in decision-making. These insights have important implications for how patient group alliances, researchers and policymakers could strengthen the engagement and contributions of RDPOs, which have become vital stakeholder groups in research.