Theoretical Formulation Strategies towards Neutralizing Inter-individual Variability Associated with Tacrolimus Immunosuppressant Therapy: A Case Study on Nextgeneration Personalized Medicine.

Individualizing drug therapy and attaining maximum benefits of a drug devoid of adverse reactions is the benefit of personalized medicine. One of the important factors contributing to inter-individual variability is genetic polymorphism. As of now, dose titration is the only followed golden standard for implementing personalized medicine. Converting the genotypic data into an optimized dose has become easier now due to technology development. However, for many drugs, finding an individualized dose may not be successful, which further leads to a trial and error approach. These dose titration strategies are generally followed at the clinical level, and so industrial involvement and further standardizations are not feasible. On the other side, technologically driven pharmaceutical industries have multiple smart drug delivery systems which are underutilized towards personalized medicine. Transdisciplinary research with drug delivery science can additionally support the personalization by converting the traditional concept of "dose titration towards personalization" with novel "dose-cum-dosage form modification towards next-generation personalized medicine"; the latter approach is useful to overcome gene-based inter-individual variability by either blocking, to downregulate, or bypassing the biological protein generated by the polymorphic gene. This article elaborates an advanced approach to implementing personalized medicine with the support of novel drug delivery systems. As a case study, we further reviewed the genetic polymorphisms associated with tacrolimus and customized novel drug delivery systems to overcome these challenges factored towards personalized medicine for better clinical outcomes, thereby paving a new strategy for implementing personalized medicine for all other drug candidates.

COVID-19 related interdisciplinary methods: Preventing errors and detecting research opportunities.

More than 130,000 peer-reviewed studies have been published within one year after COVID-19 emerged in many countries. This large and rapidly growing field may overwhelm the synthesizing abilities of both researchers and policy-makers. To provide a sinopsis, prevent errors, and detect cognitive gaps that may require interdisciplinary research methods, the literature on COVID-19 is summarized, twice. The overall purpose of this study is to generate a dialogue meant to explain the genesis of and/or find remedies for omissions and contradictions. The first review starts in Biology and ends in Policy. Policy is chosen as a destination because it is the setting where cognitive integration must occur. The second review follows the opposite path: it begins with stated policies on COVID-19 and then their assumptions and disciplinary relationships are identified. The purpose of this interdisciplinary method on methods is to yield a relational and explanatory view of the field -one strategy likely to be incomplete but usable when large bodies of literature need to be rapidly summarized. These reviews identify nine inter-related problems, research needs, or omissions, namely: (1) nation-wide, geo-referenced, epidemiological data collection systems (open to and monitored by the public); (2) metrics meant to detect non-symptomatic cases -e.g., test positivity-; (3) cost-benefit oriented methods, which should demonstrate they detect silent viral spreaders even with limited testing; (4) new personalized tests that inform on biological functions and disease correlates, such as cell-mediated immunity, co-morbidities, and immuno-suppression; (5) factors that influence vaccine effectiveness; (6) economic predictions that consider the long-term consequences likely to follow epidemics that growth exponentially; (7) the errors induced by self-limiting and/or implausible paradigms, such as binary and reductionist approaches; (8) new governance models that emphasize problem-solving skills, social participation, and the use of scientific knowledge; and (9) new educational programs that utilize visual aids and audience-specific communication strategies. The analysis indicates that, to optimally address these problems, disciplinary and social integration is needed. By asking what is/are the potential cause(s) and consequence(s) of each issue, this methodology generates visualizations that reveal possible relationships as well as omissions and contradictions. While inherently limited in scope and likely to become obsolete, these shortcomings are avoided when this 'method on methods' is frequently practiced. Open-ended, inter-/trans-disciplinary perspectives and broad social participation may help researchers and citizens to construct, de-construct, and re-construct COVID-19 related research.

From Reductionism to Reintegration: Solving society's most pressing problems requires building bridges between data types across the life sciences.

Decades of reductionist approaches in biology have achieved spectacular progress, but the proliferation of subdisciplines, each with its own technical and social practices regarding data, impedes the growth of the multidisciplinary and interdisciplinary approaches now needed to address pressing societal challenges. Data integration is key to a reintegrated biology able to address global issues such as climate change, biodiversity loss, and sustainable ecosystem management. We identify major challenges to data integration and present a vision for a "Data as a Service"-oriented architecture to promote reuse of data for discovery. The proposed architecture includes standards development, new tools and services, and strategies for career-development and sustainability.

Trends in Multidisciplinary Hazard and Disaster Research: A 1982-2017 Case Study.

From 1982 to 2017, 539 unique awards studying extreme events and natural disasters have been funded by the Infrastructure Management and Extreme Events (IMEE), Decision, Risk and Management Science (DRMS), Humans, Disasters, and the Built Environment (HDBE), and Hazard Science, Engineering, and Education for Sustainability (Hazard SEES) programs under the National Science Foundation, totaling approximately $450 million. The relationships between discipline, topic, and funding are explored through review of the data on each award's active dates, amount of funding received, specific hazards and disasters studied, and principal investigator (PI) and co-PI affiliations. A positive correlation between award funding and increasingly larger multidisciplinary teams of PIs on projects is observed. However, these teams of four or more PIs only account for about 18% of the total number of awards. In terms of topic, projects applicable to general hazard/disaster research encompass the largest portion of awards, but not the greatest funding per award on average. Additionally, both the number of awards per year and the total funds allotted per year show an increasing trend. Finally, some of the trends in project team discipline with relation to hazards show a shift to equal numbers of engineers and social scientists on multidisciplinary teams while others remain fairly homogeneous in their team dynamics. This article provides unique perspectives on how to better allocate funds through extensive topic and funding analysis. This work is a brief analysis of trends in the hazard and disaster research community, focusing on multidisciplinary project teams and their correlation to funding amounts and research areas.

Contributors to Independent Research Funding Success from the Perspective of K12 BIRCWH Program Directors.

INTRODUCTION: Faculty training awards are an important means of advancing early career faculty in research. The National Institutes of Health (NIH) Building Interdisciplinary Research Careers in Women's Health (BIRCWH) is a long-running K12 career development program and has been integral in promoting the research success of faculty nationally. We surveyed BIRCWH program directors to understand factors likely to influence long-term research careers and funding success. MATERIALS AND METHODS: We developed an online survey containing open-ended questions about individual and programmatic attributes and activities that promote success in achieving independent research funding. Domains of interest included: 1) strategies for funding success; 2) traits for predicting success; 3) groups considered vulnerable to attrition; and 4) existing resources and means of support. RESULTS: Fifteen institutions (75%) were included in the final analysis. Passion for research, persistence, resilience, and strong mentorship relationships were identified by all directors as factors important to scholar success. Responses also revealed an important pattern: program directors attributed attrition either to individual or organizational characteristics. This distinction has meaningful consequences for framing efforts to diminish attrition. Faculty who were clinicians, women, parents and underrepresented minorities were identified as vulnerable to attrition from the research careers. Common perceived challenges in these groups included isolation/feeling alienated, juggling numerous priorities, inadequate research time, lack of role models, and work-life balance issues. CONCLUSION: K12 BIRCWH directors identified persistence and resilience and developing community, networks, and other support opportunities as elements of scholar success. Programs and mentors can help early career faculty by teaching skills and providing tools they can use to maximize the value of these opportunities and expand their mentees' research relationships. Our study also highlights the importance of social factors, particularly isolation, on clinicians, women, and minoritized scholars on career success.

Exploring the changing geographical pattern of international scientific collaborations through the prism of cities.

Science is becoming increasingly international in terms of breaking down walls in its pursuit of high impact. Despite geographical location and distance still being major barriers for scientific collaboration, little is known about whether high-impact collaborations are similarly constrained by geography compared to collaborations of average impact. To address this question, we analyze Web of Science (WoS) data on international collaboration between global leader cities in science production. We report an increasing intensity of international city-city collaboration and find that average distance of collaboration of the strongest connections has slightly increased, but distance decay has remained stable over the last three decades. However, high-impact collaborations span large distances by following similar distance decay. This finding suggests that a larger geographical reach of research collaboration should be aimed for to support high-impact science. The creation of the European Research Area (ERA) represents an effective action that has deepened intracontinental research collaborations and the position of the European Union (EU) in global science. Yet, our results provide new evidence that global scientific leaders are not sufficiently collaborative in carrying out their big science projects.

Advances in the diagnosis of inherited neuromuscular diseases and implications for therapy development.

Advances in DNA sequencing technologies have resulted in a near doubling, in under 10 years, of the number of causal genes identified for inherited neuromuscular disorders. However, around half of patients, whether children or adults, do not receive a molecular diagnosis after initial diagnostic workup. Massively parallel technologies targeting RNA, proteins, and metabolites are being increasingly used to diagnose these unsolved cases. The use of these technologies to delineate pathways, biomarkers, and therapeutic targets has led to new approaches entering the drug development pipeline. However, these technologies might give rise to misleading conclusions if used in isolation, and traditional techniques including comprehensive neurological evaluation, histopathology, and biochemistry continue to have a crucial role in diagnostics. For optimal diagnosis, prognosis, and precision medicine, no single ruling technology exists. Instead, an interdisciplinary approach combining novel and traditional neurological techniques with computer-aided analysis and international data sharing is needed to advance the diagnosis and treatment of neuromuscular disorders.

The role of team science in the future of male contraception†.

Efforts to develop a male contraceptive method beyond condoms and vasectomy have been on-going for nearly 70 years. During this time, there have been ebbs and modest flows of resources available to support product development, but not at a level sufficient to carry research efforts through to market. The small community of researchers that have continued to pursue the development of male contraceptives is comprised of dedicated scientists who have a great deal of knowledge and experience to offer. While collaboration has been an organic outcome of limited resources, competing research objectives and geographically diverse locations have made consistent and sustained progress challenging, particularly for those working in the earliest stages of developing nonhormonal, reversible male contraceptive methods. While the past decade has seen an increase in funding to the field, the levels are still modest when placed in the context of actual costs to bring products to market. In addition, there are challenges still to be identified given that there is no regulatory precedent for these products. These challenges present an excellent use case for the application of design-thinking or human centered design, as a means of generating novel solutions. By engaging those with deep technical expertise in the field of male contraception as well as thought leaders from other fields of practice, design-thinking offers an opportunity to identify potential strategies, including nontraditional approaches, capable of driving the product development process forward, in a faster and more efficient manner.

Approaches to Measuring Trends in Interdisciplinary Research Publications at One Academic Medical Center.

PURPOSE: To determine if interdisciplinary research has increased between 2005 and 2015, based on an analysis of journal articles containing at least 1 author from Johns Hopkins University, and to compare different methods for determining the disciplinarity of research articles. METHOD: In 2017-2018, 100 peer-reviewed biomedical science articles were randomly selected from years 2005, 2010, and 2015 and classified as unidisciplinary or interdisciplinary based on Scopus author affiliation data (method 1). The corresponding authors of the 2010 and 2015 articles were sent a survey asking them to describe the disciplines involved in their research (method 2) and to define their research as unidisciplinary or interdisciplinary based on provided definitions (method 3). RESULTS: There was a statistically significant increase in the proportion of interdisciplinary articles in 2015 compared with both 2005 and 2010 (P = .02). Comparison of the 3 methods indicated that 45% of the articles were classified as interdisciplinary based on author affiliation data (method 1), 40% based on the corresponding author's description of the disciplines involved in their research (method 2), and 71% based on the corresponding author's definition of their article's disciplinarity (method 3). There was a statistically significant difference in the proportion of articles classified as interdisciplinary between methods 1 and 3 (P < .001) and between methods 2 and 3 (P < .001). CONCLUSIONS: This study found that interdisciplinary research increased at Johns Hopkins University over the past decade and highlights the difference between corresponding authors' views of their own research and other methods for determining interdisciplinarity.