Efficacy of Centers of Biomedical Research Excellence (CoBRE) grants to build research capacity in underrepresented states.

Federal funding for research has immediate and long-term economic impact. Since federal research funding is regionally concentrated and not geographically distributed, the benefits are not fully realized in some regions of the country. The Established (previously Experimental) Program to Stimulate Competitive Research (EPSCoR) programs at several agencies, for example, the National Science Foundation, and the Institutional Development Award (IDeA) program at the National Institutes of Health were created to increase competitiveness for funding in states with historically low levels of federal funding. The Centers of Biomedical Research Excellence (CoBRE) award program is a component of the IDeA program. The CoBRE grants support research core facilities to develop research infrastructure. These grants also support the research projects of junior investigators, under the guidance of mentoring teams of senior investigators, to develop human resources at these institutions. Few studies have assessed the effectiveness of these programs. This study examines the investment and outcomes of the CoBRE grants from 2000 through 2022. The maturation of junior investigators into independently funded principal investigators is comparable to other mentoring programs supported by NIH. The investment in research cores resulted in substantial research productivity, measured by publications. Despite the successes of individual investigators and increased research infrastructure and productivity, the geographic distribution of federal and NIH research dollars has not changed. These results will be informative in consideration of policies designed to enhance the geographic distribution of federal research dollars.

Setting up a state-of-the-art laboratory in resource limited settings: A case study of the biomedical science research and training centre in Northeast Nigeria.

African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research and Training Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to overcome current barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation and collaborations. With its state-of-the-art facilities and commitment to training African scientists, BioRTC is poised to significantly advance neuroscience research and training in the region. Although we are in the early stages of our journey, our model, emphasizing open access and inclusivity, offers a replicable blueprint for neuroscience research development in similar resource-limited settings, promising to enrich the global neuroscience community. We invite the support and collaboration of those who share our vision and believe in our potential.

Managing the life cycle of a portfolio of open data resources at the SIB Swiss Institute of Bioinformatics.

Data resources are essential for the long-term preservation of scientific data and the reproducibility of science. The SIB Swiss Institute of Bioinformatics provides the life science community with a portfolio of openly accessible, high-quality databases and software platforms, which vary from expert-curated knowledgebases, such as UniProtKB/Swiss-Prot (part of the UniProt consortium) and STRING, to online platforms such as SWISS-MODEL and SwissDrugDesign. SIB's mission is to ensure that these resources are available in the long term, as long as their return on investment and their scientific impact are high. To this end, SIB provides its resources, in addition to stable financial support, with a range of high-quality, innovative services that are, to our knowledge, unique in the field. Through this first-class management framework with central services, such as user-centric consulting activities, legal support, open-science guidance, knowledge sharing and training efforts, SIB supports the promotion of excellence in resource development and operation. This review presents the ecosystem of data resources at SIB; the process used for the identification, evaluation and development of resources; and the support activities that SIB provides. A set of indicators has been put in place to select the resources and establish quality standards, reflecting their multifaceted nature and complexity. Through this paper, the reader will discover how SIB's leading tools and databases are fostered by the institute, leading them to be best-in-class resources able to tackle the burning matters that society faces from disease outbreaks and cancer to biodiversity and open science.

Sustaining productivity gains in the face of climate change: A research agenda for US wheat.

Wheat is a globally important crop and one of the "big three" US field crops. But unlike the other two (maize and soybean), in the United States its development is commercially unattractive, and so its breeding takes place primarily in public universities. Troublingly, the incentive structures within these universities may be hindering genetic improvement just as climate change is complicating breeding efforts. "Business as usual" in the US public wheat-breeding infrastructure may not sustain productivity increases. To address this concern, we held a multidisciplinary conference in which researchers from 12 US (public) universities and one European university shared the current state of knowledge in their disciplines, aired concerns, and proposed initiatives that could facilitate maintaining genetic improvement of wheat in the face of climate change. We discovered that climate-change-oriented breeding efforts are currently considered too risky and/or costly for most university wheat breeders to undertake, leading to a relative lack of breeding efforts that focus on abiotic stressors such as drought and heat. We hypothesize that this risk/cost burden can be reduced through the development of appropriate germplasm, relevant screening mechanisms, consistent germplasm characterization, and innovative models predicting the performance of germplasm under projected future climate conditions. However, doing so will require coordinated, longer-term, inter-regional efforts to generate phenotype data, and the modification of incentive structures to consistently reward such efforts.

The BioRef Infrastructure, a Framework for Real-Time, Federated, Privacy-Preserving, and Personalized Reference Intervals: Design, Development, and Application.

BACKGROUND: Reference intervals (RIs) for patient test results are in standard use across many medical disciplines, allowing physicians to identify measurements indicating potentially pathological states with relative ease. The process of inferring cohort-specific RIs is, however, often ignored because of the high costs and cumbersome efforts associated with it. Sophisticated analysis tools are required to automatically infer relevant and locally specific RIs directly from routine laboratory data. These tools would effectively connect clinical laboratory databases to physicians and provide personalized target ranges for the respective cohort population. OBJECTIVE: This study aims to describe the BioRef infrastructure, a multicentric governance and IT framework for the estimation and assessment of patient group-specific RIs from routine clinical laboratory data using an innovative decentralized data-sharing approach and a sophisticated, clinically oriented graphical user interface for data analysis. METHODS: A common governance agreement and interoperability standards have been established, allowing the harmonization of multidimensional laboratory measurements from multiple clinical databases into a unified "big data" resource. International coding systems, such as the International Classification of Diseases, Tenth Revision (ICD-10); unique identifiers for medical devices from the Global Unique Device Identification Database; type identifiers from the Global Medical Device Nomenclature; and a universal transfer logic, such as the Resource Description Framework (RDF), are used to align the routine laboratory data of each data provider for use within the BioRef framework. With a decentralized data-sharing approach, the BioRef data can be evaluated by end users from each cohort site following a strict "no copy, no move" principle, that is, only data aggregates for the intercohort analysis of target ranges are exchanged. RESULTS: The TI4Health distributed and secure analytics system was used to implement the proposed federated and privacy-preserving approach and comply with the limitations applied to sensitive patient data. Under the BioRef interoperability consensus, clinical partners enable the computation of RIs via the TI4Health graphical user interface for query without exposing the underlying raw data. The interface was developed for use by physicians and clinical laboratory specialists and allows intuitive and interactive data stratification by patient factors (age, sex, and personal medical history) as well as laboratory analysis determinants (device, analyzer, and test kit identifier). This consolidated effort enables the creation of extremely detailed and patient group-specific queries, allowing the generation of individualized, covariate-adjusted RIs on the fly. CONCLUSIONS: With the BioRef-TI4Health infrastructure, a framework for clinical physicians and researchers to define precise RIs immediately in a convenient, privacy-preserving, and reproducible manner has been implemented, promoting a vital part of practicing precision medicine while streamlining compliance and avoiding transfers of raw patient data. This new approach can provide a crucial update on RIs and improve patient care for personalized medicine.

Swiss CAT+, a Data-driven Infrastructure for Accelerated Catalysts Discovery and Optimization.

The Catalysis Hub - Swiss CAT+ is a new infrastructure project funded by ETH-domain, co-headed by EPFL and ETHZ. It offers the scientific community a unique integrated technology platform combining automated and high-throughput experimentation with advanced computational data analysis to accelerate the discoveries in the field of sustainable catalytic technologies. Divided into two hubs of expertise, homogeneous catalysis at EPFL and heterogeneous catalysis at ETHZ, the platform is open to academic and private research groups. Following a multi-year investment plan, both hubs have acquired and developed several high-end robotic platforms devoted to the synthesis, characterization, and testing of large numbers of molecular and solid catalysts. The hardware is associated with a fully digitalized experimental workflow and a specific data management strategy to support closed-loop experimentation and advanced computational data analysis.

[The German Network of University Medicine: technical and organizational approaches for research data platforms]. / Das Netzwerk Universitätsmedizin: Technisch-organisatorische Ansätze für Forschungsdatenplattformen.

The Network University Medicine (NUM) consists of 36 university clinics in Germany. It was set up to coordinate COVID-19 university medicine research activities on a national level. This required, among other things, common infrastructures for the collection, storage, and use of medical research data. These infrastructures were not available in the required form when the NUM started in April 2020. Medical research data are extremely heterogeneous and reach far beyond "real world data" from patient care. There was no "one size fits all" solution, so NUM built five infrastructures for different types of data, different ways of obtaining data, and different data origination settings. To prevent the creation of new data silos, all five infrastructures operate based on FAIR principles (findable, accessible, interoperable, reusable). In addition, NUM is implementing an overarching governance framework to manage the evolution of these five infrastructures. The article describes the current state of development and possible perspectives with a strong focus on technical and organizational aspects.

The EurOPDX Data Portal: an open platform for patient-derived cancer xenograft data sharing and visualization.

BACKGROUND: Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research. EurOPDX Data Portal is the unified data sharing platform adopted by the Consortium. MAIN BODY: In this paper we describe the main features of the EurOPDX Data Portal ( https://dataportal.europdx.eu/ ), its architecture and possible utilization by researchers who look for PDX mice models for their research. The Portal offers a catalogue of European models accessible on a cooperative basis. The models are searchable by metadata, and a detailed view provides molecular profiles (gene expression, mutation, copy number alteration) and treatment studies. The Portal displays the data in multiple tools (PDX Finder, cBioPortal, and GenomeCruzer in future), which are populated from a common database displaying strictly mutually consistent views. (SHORT) CONCLUSION: EurOPDX Data Portal is an entry point to the EurOPDX Research Infrastructure offering PDX mice models for collaborative research, (meta)data describing their features and deep molecular data analysis according to users' interests.

European research networks to facilitate drug research in children.

Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

Improving the outcome for children with cancer: Development of targeted new agents.

The outcome for children with cancer has improved significantly over the past 60 years, with greater than 80% of patients today becoming 5-year survivors. Despite this progress, cancer remains the leading cause of death from disease in children in the United States, and significant short-term and long-term treatment toxicities continue to impact the majority of children with cancer. The development of targeted new agents offers the prospect of potentially more effective and less toxic treatment for children. More than a decade since imatinib mesylate was introduced into the treatment of children with Philadelphia chromosome-positive acute lymphoblastic leukemia, transforming its outcome, a range of targeted agents has undergone study in pediatric cancer patients. Early lessons learned from these studies include a better understanding of the adverse event profile of these drugs in children, the challenge of developing pediatric-specific formulations, and the continued reliance on successful development for adult cancer indications on pediatric drug development. The collaborative research infrastructure for children with cancer in the United States is well positioned to advance novel treatments into clinical investigations for a spectrum of rare and ultra-rare childhood cancers. A greater investment of resources in target discovery and validation can help drive much needed development of new, more effective treatments for children with cancer.

The COVID-19 pandemic has highlighted the need to invest in care home research infrastructure.

The COVID-19 pandemic resulted in catastrophic levels of morbidity and mortality for care home residents. Despite this, research platforms for COVID-19 in care homes arrived late in the pandemic compared with other care settings. The Prophylactic Therapy in Care Homes Trial (PROTECT-CH) was established to provide a platform to deliver multi-centre cluster-randomized clinical trials of investigational medicinal products for COVID-19 prophylaxis in UK care homes. Commencing set-up in January 2021, this involved the design and development of novel infrastructure for contracting and recruitment, remote consent, staff training, research insurance, eligibility screening, prescribing, dispensing and adverse event reporting; such infrastructure being previously absent. By the time this infrastructure was in place, the widespread uptake of vaccination in care homes had changed the epidemiology of COVID-19 rendering the trial unfeasible. While some of the resources developed through PROTECT-CH will enable the future establishment of care home platform research, the near absence of care home trial infrastructure and nationally linked databases involving the care home sector will continue to significantly hamper progress. These issues are replicated in most other countries. Beyond COVID-19, there are many other research questions that require addressing to provide better care to people living in care homes. PROTECT-CH has exposed a clear need for research funders to invest in, and legislate for, an effective care home research infrastructure as part of national pandemic preparedness planning. Doing so would also invigorate care home research in the interim, leading to improved healthcare delivery specific to those living in this sector.

HIV HGM biobank as a research platform for paediatric infectious diseases and COVID-19 pandemic.

AIM: The initial cases of COVID-19 appeared in December 2019 and Spain was one of the most affected countries during the first wave (March to June). Since then, HIV HGM BioBank has been restructured as an established Paediatrics and Adults HIV_COVID-19 BioBank that aims at the long-term storage of samples obtained from not only HIV-1, but also from COVID-19 patients and HIV-1_COVID-19 coinfected patients. METHODS: HIV HGM BioBank holds high quality biological samples from newborns, children, adolescents and adults with their associated clinical data. Research groups trying to establish large networks focused on research on specific clinical problems in epidemiology, biology, routes of transmission and therapies, are potential users of the clinical samples and of associated data of HIV-1_COVID-19 HGM BioBank. RESULTS: The HIV HGM BioBank is an academic and ethical enterprise complying with all the legal regulatory rules to provide service to the society. HIV_COVID-19 HGM BioBank has been repurposed to offer an important resource for global research of COVID-19 in newborns, children, adolescents, adults and elders to study the biological effect of the pandemic. CONCLUSION: Herein, we present a description of how HIV HGM BioBank has rapidly become an indispensable structure in modern biomedical research, including COVID-19 research.

A gaps-and-needs analysis of vaccine R&D in Europe: Recommendations to improve the research infrastructure.

The COVID-19 pandemic has brought into sharp focus the importance of strategies supporting vaccine development. During the pandemic, TRANSVAC, the European vaccine-research-infrastructure initiative, undertook an in-depth consultation of stakeholders to identify how best to position and sustain a European vaccine R&D infrastructure. The consultation included an online survey incorporating a gaps-and-needs analysis, follow-up interviews and focus-group meetings. Between October 2020 and June 2021, 53 organisations completed the online survey, including 24 research institutes and universities, and 9 pharmaceutical companies; 24 organisations participated in interviews, and 14 in focus-group meetings. The arising recommendations covered all aspects of the vaccine-development value chain: from preclinical development to financing and business development; and covered prophylactic and therapeutic vaccines, for both human and veterinary indications. Overall, the recommendations supported the expansion and elaboration of services including training programmes, and improved or more extensive access to expertise, technologies, partnerships, curated databases, and-data analysis tools. Funding and financing featured as critical elements requiring support throughout the vaccine-development programmes, notably for academics and small companies, and for vaccine programmes that address medical and veterinary needs without a great potential for commercial gain. Centralizing the access to these research infrastructures via a single on-line portal was considered advantageous.

FarGen - participants in the genetic research infrastructure of the Faroe Islands.

Background: The demographic history of the Faroe Islands makes this isolated population - founded in the 9th century - interesting for genetic research. The goal of the FarGen project was to recruit individuals to the FarGen infrastructure to promote research into the genetic features of the Faroese people, and to develop a reference panel of population-specific variants. We aimed to recruit 1500 individuals. Participation was voluntary; participants had to donate a blood sample for whole-genome sequencing, and had to answer a questionnaire regarding sociodemographics, health, motivation and attitude towards participation in genetic research. Methods: A total of 1541 participants voluntarily joined the project, donated a blood sample and returned the questionnaire. Results: Answers from the questionnaire show that participants are, in general, European, have children, have a relatively high level of education, rate their health to be good, are willing to participate in future health-related research, and were motivated to sign up primarily to participate in research to help others and local research competency building. Conclusions: Overall, the initial cohort of the FarGen infrastructure comprises 3% of the Faroese population, and represents the general population well based on the collected sociodemographic data. However, there is an excess of women, and some geographic sub-regions and age groups are slightly underrepresented. We find the recruitment method with voluntary sign-up appropriate, and knowledge acquired through the first phase will aid the next phase of the project, with the aim of expanding the FarGen cohort with additional individuals, bio-specimens and body measurements in order to perform multifactorial analyses.

Establishment of the Dutch Nationwide, Interdisciplinary Infrastructure and Biobank for Fundamental and Translational Ovarian Cancer Research: Archipelago of Ovarian Cancer Research.

OBJECTIVES: Ovarian cancer has the worst overall survival rate of all gynecologic malignancies. For the majority of patients, the 5-year overall survival rate of less than 50% has hardly improved over the last decades. To improve the outcome of patients with all subtypes of ovarian cancer, large-scale fundamental and translational research is needed. To accommodate these types of ovarian cancer research, we have established a Dutch nationwide, interdisciplinary infrastructure and biobank: the Archipelago of Ovarian Cancer Research (AOCR). The AOCR will facilitate fundamental and translational ovarian cancer research and enhance interdisciplinary, national, and international collaboration. DESIGN: The AOCR biobank is a prospective ovarian cancer biobank in which biomaterials are collected, processed, and stored in a uniform matter for future (genetic) scientific research. All 19 Dutch hospitals in which ovarian cancer surgery is performed participate and collaborate in the AOCR biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients of 16 years and older with suspected or diagnosed ovarian, fallopian tube, or primary peritoneal cancer are recruited for participation. Patients who agree to participate give written informed consent for collection, storage, and issue of their biomaterials for future studies. After inclusion, different blood samples are taken at various predefined time points both before and during treatment. In case of a diagnostic paracentesis or biopsy, the residual biomaterials of these procedures are stored in the biobank. During surgery, primary tumor tissue and, if applicable, tissue from metastatic sites are collected and stored. From each patient, a representative histological hematoxylin and eosin stained slide is digitalized for research purposes, including reassessment by a panel of gynecologic pathologists. Clinical and pathological data are obtained on a per-study basis from Dutch registries. Research proposals for the issue of biomaterials and data are evaluated by both the Archipelago Scientific Committee and the Steering Committee. Researchers using the biomaterials from the AOCR biobank are encouraged to enrich the biobank with data and materials resulting from their analyses and experiments. LIMITATIONS: The implementation and first 4 years of collection are financed by an infrastructural grant from the Dutch Cancer Society. Therefore, the main limitation is that the costs for sustaining the biobank after the funding period will have to be covered. This coverage will come from incorporation of budget for biobanking in future grant applications and from fees from external researchers and commercial parties using the biomaterials stored in the AOCR biobank. Moreover, we will apply for grants aimed at sustaining and improving research infrastructures and biobanks. CONCLUSIONS: With the establishment of the Dutch nationwide, interdisciplinary Archipelago of Ovarian Cancer Research infrastructure and biobank, fundamental and translational research on ovarian cancer can be greatly improved. The ultimate aim of this infrastructure is that it will lead to improved diagnostics, treatment, and survival of patients with ovarian cancer.

Bioinformatics in the Netherlands: the value of a nationwide community.

This review provides a historical overview of the inception and development of bioinformatics research in the Netherlands. Rooted in theoretical biology by foundational figures such as Paulien Hogeweg (at Utrecht University since the 1970s), the developments leading to organizational structures supporting a relatively large Dutch bioinformatics community will be reviewed. We will show that the most valuable resource that we have built over these years is the close-knit national expert community that is well engaged in basic and translational life science research programmes. The Dutch bioinformatics community is accustomed to facing the ever-changing landscape of data challenges and working towards solutions together. In addition, this community is the stable factor on the road towards sustainability, especially in times where existing funding models are challenged and change rapidly.

Lessons from the pandemic on the value of research infrastructure.

The COVID-19 pandemic has shed a spotlight on the resilience of healthcare systems, and their ability to cope efficiently and effectively with unexpected crises. If we are to learn one economic lesson from the pandemic, arguably it is the perils of an overfocus on short-term allocative efficiency at the price of lack of capacity to deal with uncertain future challenges. In normal times, building spare capacity with 'option value' into health systems may seem inefficient, the costs potentially exceeding the benefits. Yet the fatal weakness of not doing so is that this can leave health systems highly constrained when dealing with unexpected, but ultimately inevitable, shocks-such as the COVID-19 pandemic. In this article, we argue that the pandemic has highlighted the potentially enormous option value of biomedical research infrastructure. We illustrate this with reference to COVID-19 response work supported by the United Kingdom National Institute for Health Research Oxford Biomedical Research Centre. As the world deals with the fallout from the most serious economic crisis since the Great Depression, pressure will soon come to review government expenditure, including research funding. Developing a framework to fully account for option value, and understanding the public appetite to pay for it, should allow us to be better prepared for the next emerging problem.

Fundamental challenges in assessing the impact of research infrastructure.

Clinical research infrastructure is one of the unsung heroes of the scientific response to the current COVID-19 pandemic. The extensive, long-term funding into research support structures, skilled people, and technology allowed the United Kingdom research response to move off the starting blocks at pace by utilizing pre-existing platforms. The increasing focus from funders on evaluating the outcomes and impact of research infrastructure investment requires both a reframing and progression of the current models in order to address the contribution of the underlying support infrastructure. The majority of current evaluation/outcome models focus on a "pipeline" approach using a methodology which follows the traditional research funding route with the addition of quantitative metrics. These models fail to embrace the complexity caused by the interplay of previous investment, the coalescing of project outputs from different funders, the underlying infrastructure investment, and the parallel development across different parts of the system. Research infrastructure is the underpinning foundation of a project-driven research system and requires long-term, sustained funding and capital investment to maintain scientific and technological expertise. Therefore, the short-term focus on quantitative metrics that are easy to collect and interpret and that can be assessed in a roughly 5-year funding cycle needs to be addressed. The significant level of investment in research infrastructure necessitates investment to develop bespoke methodologies that develop fit-for-purpose, longer-term/continual approach(es) to evaluation. Real-world research should reflect real-world evaluation and allow for the accrual of a narrative of value indicators that build a picture of the contribution of infrastructure to research outcomes. The linear approach is not fit for purpose, the research endeavour is a complex, twisted road, and the evaluation approach needs to embrace this complexity through the development of realist approaches and the rapidly evolving data ecosystem. This paper sets out methodological challenges and considers the need to develop bespoke methodological approaches to allow a richer assessment of impact, contribution, attribution, and evaluation of research infrastructure. This paper is the beginning of a conversation that invites the community to "take up the mantle" and tackle the complexity of real-world research translation and evaluation.

Developing an interprofessional research infrastructure at a mid-sized liberal arts university.

This Interprofessional Education and Practice (IPEP) Guide describes the various mechanisms used to grow and support interprofessional research and scholarship at a mid-sized liberal arts university. The guide illustrates a creative, multi-stakeholder approach to integrating interprofessional education into university departments and programs and offers suggestions for establishing a research infrastructure that centers interprofessional scholarly engagement and is aligned with the institution's missions and values. Faculty and higher education practitioners are provided with key takeaways for crafting an internal grants program to achieve these goals.

Assessing the biogeographical and socio-ecological representativeness of the ILTER site network.

The challenges posed by climate and land use change are increasingly complex, with rising and accelerating impacts on the global environmental system. Novel environmental and ecosystem research needs to properly interpret system changes and derive management recommendations across scales. This largely depends on advances in the establishment of an internationally harmonised, long-term operating and representative infrastructure for environmental observation. This paper presents an analysis evaluating 743 formally accredited sites of the International Long-Term Ecological Research (ILTER) network in 47 countries with regard to their spatial distribution and related biogeographical and socio-ecological representativeness. "Representedness" values were computed from six global datasets. The analysis revealed a dense coverage of Northern temperate regions and anthropogenic zones most notably in the US, Europe and East Asia. Significant gaps are present in economically less developed and anthropogenically less impacted hot and barren regions like Northern and Central Africa and inner-continental parts of South America. These findings provide the arguments for our recommendations regarding the geographic expansion for the further development of the ILTER network.