Opportunities For Biomedical Research Research Articles

Our undergraduate program for physiology research, UPRIME (Undergraduate Physiology In Medicine and Education) will continue and further encourage and foster our majors in Human Physiology to enter careers in the health professions and physiology research

We previously announced and reported on our undergraduate summer research program, UPRIME, funded by an American Heart Association Grant with departmental support, has been successful in the fostering of junior and senior undergraduates (UPRIME Scholars) for the health professions and research. UPRIME is a 13-week summer program that provides opportunities for biomedical research, educational support and career advising. Our hope is that this holistic approach builds a space for inclusive excellence in which UPRIME scholars can acquire the tools needed for success. During the past three years, we have selected UPRIME Scholars based on the strength of their applications. We have matched the research interests of the students with our departmental strengths and met with the scholars weekly to foster a peer-based community and augment their research efforts with scientific seminars and discussions. Additionally, our UPRIME Scholars were supported to present their work at local and national level meetings. Our companion program, INPUT (INtegrative Biology & Physiology Undergraduate Training) which is designed for freshmen and sophomores with strong interest in physiology, is also part of our department’s commitment to inclusive excellence. Here, we are updating the statuses of previous and current UPRIME Scholars. Previous UPRIME Scholars have graduated and entered either professional schools (including medical and dental) or continue to work in our research labs. In addition, our most recent 2023 UPRIME Scholars that will graduate between 2023 and 2024 are currently still working in their mentors’ labs. Our department will continue to support UPRIME. In addition, we are committed to expanding our program to the regional and national levels. We seek highly motivated applicants from around the nation to apply to UPRIME for the opportunity to gain meaningful experiences in physiology research. American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hepatic organoids move from adolescence to maturity.

Since organoids were developed 15 years ago, they are now in their adolescence as a research tool. The ability to generate 'tissue in a dish' has created enormous opportunities for biomedical research. We examine the contributions that hepatic organoids have made to three areas of liver research: as a source of cells and tissue for basic research, for drug discovery and drug safety testing, and for understanding disease pathobiology. We discuss the features that enable hepatic organoids to provide useful models for human liver diseases and identify four types of advances that will enable them to become a mature (i.e., adult) research tool over the next 5 years. During this period, advances in single-cell RNA sequencing and CRISPR technologies coupled with improved hepatic organoid methodology, which enables them to have a wider range of cell types that are present in liver and to be grown in microwells, will generate discoveries that will dramatically advance our understanding of liver development and the pathogenesis of liver diseases. It will generate also new approaches for treating liver fibrosis, which remains a major public health problem with few treatment options.

Copper-Single-Atom Coordinated Nanotherapeutics for Enhanced Sonothermal-Parallel Catalytic Synergistic Cancer Therapy.

Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel "BH" interfacial-confined coordination strategy to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes (HA-NC_Cu) to achieve sonothermal-catalytic synergistic therapy is reported. Notably, HA-NC_Cu demonstrates exceptional sonothermal conversion performance under low-intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high-toxicity hydroxyl radicals in response to tumor-endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA-NC_Cu originates from the CuN4 C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal-catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long-term survival rate (100%). In combination with low-intensity ultrasound irradiation, HA-NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA-MB-231 breast cancer cells, comprehensively limiting primary triple-negative breast cancer. This study highlights the applications of single-atom-coordinated nanotherapeutics in sonothermal-catalytic synergistic therapy, which may create new opportunities in biomedical research.

Developing Future Biologists: developmental biology for undergraduates from underserved communities.

Developing Future Biologists (DFB) is an inclusive, trainee-run organization that strives to excite and engage the next generation of biologists, regardless of race, gender or socioeconomic status, in the field of developmental biology. DFB offers a week-long course consisting of active lectures, hands-on laboratory sessions, and professional development opportunities through interactions with scientists from a variety of backgrounds and careers. A major goal of DFB is to propel undergraduate students from underserved communities to pursue biomedical research opportunities and advanced degrees in science. To achieve this goal, we provide DFB participants with continuing access to a diverse network of scientists that students can utilize to secure opportunities and foster success throughout multiple stages of their research careers. Here, we describe the flourishing DFB program at the University of Michigan to encourage other institutions to create their own DFB programs.

Micro-computed tomography for analysis of heavy metal accumulation in the opercula

Micro-computed tomography (micro-CT) provides numerous opportunities in biomedical research. It allows the examination of samples in a non-destructive manner and visualization of the inner structures of various biological and nonbiological objects. This study was conducted to evaluate the potential of micro-CT scanner in the assessment of heavy metal accumulation in the opercula. The samples were taken from Prussian carp (Carassius gibelio) exposed to waterborne Cd (4.0 mg/L), Zn (4.0 mg/L), and the mixture of these two metals (4.0 mg Cd/L and 4.0 mg Zn/L) for 28 days. Heavy metal concentrations were determined using atomic absorption spectrometry. The results demonstrated higher concentrations of Cd and Zn in the treatment group opercula samples compared with the control group opercula samples. A simple micro-CT scan was performed to verify whether heavy metal accumulation could be determined in the reconstructed images. The results showed that micro-CT is potentially a powerful tool for metal accumulation detection. Moreover, it allowed visualization of the examined samples, revealing regions of heavy metal accumulation and providing the opportunity to compare samples exposed to different types of heavy metals.

Versatile Types of Inorganic/Organic NIR-IIa/IIb Fluorophores: From Strategic Design toward Molecular Imaging and Theranostics.

In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.

Recent Advances in Variational Autoencoders With Representation Learning for Biomedical Informatics: A Survey

Variational autoencoders (VAEs) are deep latent space generative models that have been immensely successful in multiple exciting applications in biomedical informatics such as molecular design, protein design, medical image classification and segmentation, integrated multi-omics data analyses, and large-scale biological sequence analyses, among others. The fundamental idea in VAEs is to learn the distribution of data in such a way that new meaningful data with more intra-class variations can be generated from the encoded distribution. The ability of VAEs to synthesize new data with more representation variance at state-of-art levels provides hope that the chronic scarcity of labeled data in the biomedical field can be resolved. Furthermore, VAEs have made nonlinear latent variable models tractable for modeling complex distributions. This has allowed for efficient extraction of relevant biomedical information from learned features for biological data sets, referred to as unsupervised feature representation learning. In this article, we review the various recent advancements in the development and application of VAEs for biomedical informatics. We discuss challenges and future opportunities for biomedical research with respect to VAEs.

PheWAS-ME: a web-app for interactive exploration of multimorbidity patterns in PheWAS.

Electronic health records (EHRs) linked with a DNA biobank provide unprecedented opportunities for biomedical research in precision medicine. The Phenome-wide association study (PheWAS) is a widely used technique for the evaluation of relationships between genetic variants and a large collection of clinical phenotypes recorded in EHRs. PheWAS analyses are typically presented as static tables and charts of summary statistics obtained from statistical tests of association between a genetic variant and individual phenotypes. Comorbidities are common and typically lead to complex, multivariate gene-disease association signals that are challenging to interpret. Discovering and interrogating multimorbidity patterns and their influence in PheWAS is difficult and time-consuming. We present PheWAS-ME: an interactive dashboard to visualize individual-level genotype and phenotype data side-by-side with PheWAS analysis results, allowing researchers to explore multimorbidity patterns and their associations with a genetic variant of interest. We expect this application to enrich PheWAS analyses by illuminating clinical multimorbidity patterns present in the data. A demo PheWAS-ME application is publicly available at https://prod.tbilab.org/phewas_me/. Sample datasets are provided for exploration with the option to upload custom PheWAS results and corresponding individual-level data. Online versions of the appendices are available at https://prod.tbilab.org/phewas_me_info/. The source code is available as an R package on GitHub (https://github.com/tbilab/multimorbidity_explorer). Supplementary data are available at Bioinformatics online.

Morocco's First Biobank: Establishment, Ethical Issues, Biomedical Research Opportunities, and Challenges.

Background Biobanks are highly organized infrastructures that allow the storage of human biological specimens associated with donors' personal and clinical data. These infrastructures play a key role in the development of translational medical research. In this context, we launched, in November 2015, the first biobank in Morocco (BRO Biobank) in order to promote biomedical research and provide opportunities to include Moroccan and North African ethnic groups in international biomedical studies. Here, we present the setup and the sample characteristics of BRO Biobank. Methods Patients were recruited at several departments of two major health-care centers in the city of Oujda. Healthy donors were enrolled during blood donation campaigns all over Eastern Morocco. From each participant, personal, clinical, and biomedical data were collected, and several biospecimens were stored. Standard operating procedures have been established in accordance with international guidelines on human biobanks. Results Between November 2015 and July 2020, 2446 participants were recruited into the BRO Biobank, of whom 2013 were healthy donors, and 433 were patients. For healthy donors, the median age was 35 years with a range between 18 and 65 years and the consanguinity rate was 28.96%. For patients, the median age was 11 years with a range between 1 day and 83 years. Among these patients, 55% had rare diseases (hemoglobinopathies, intellectual disabilities, disorders of sex differentiation, myopathies, etc.), 13% had lung cancer, 4% suffered from hematological neoplasms, 3% were from the kidney transplantation project, and 25% had unknown diagnoses. The BRO Biobank has collected 5092 biospecimens, including blood, white blood cells, plasma, serum, urine, frozen tissue, FFPE tissue, and nucleic acids. A sample quality control has been implemented and suggested that samples of the BRO Biobank are of high quality and therefore suitable for high-throughput nucleic acid analysis. Conclusions The BRO Biobank is the largest sample collection in Morocco, and it is ready to provide samples to national and international research projects. Therefore, the BRO Biobank is a valuable resource for advancing translational medical research.

ANESTHESIOLOGY 2020 Keynote Address: ‘Exceptional Opportunities in Biomedical Research’

ANESTHESIOLOGY 2020 Keynote Address: ‘Exceptional Opportunities in Biomedical Research’

Delivery of Tissue-Targeted Scalpels: Opportunities and Challenges for In Vivo CRISPR/Cas-Based Genome Editing.

CRISPR/Cas9-based genome editing has quickly emerged as a powerful breakthrough technology for use in diverse settings across biomedical research and therapeutic development. Recent efforts toward understanding gene modification methods in vitro have led to substantial improvements in ex vivo genome editing efficiency. Because disease targets for genomic correction are often localized in specific organs, realization of the full potential of genomic medicines will require delivery of CRISPR/Cas9 systems targeting specific tissues and cells directly in vivo. In this Perspective, we focus on progress toward in vivo delivery of CRISPR/Cas components. Viral and nonviral delivery systems are both promising for gene editing in diverse tissues via local injection and systemic injection. We describe the various viral vectors and synthetic nonviral materials used for in vivo gene editing and applications to research and therapeutic models, and summarize opportunities and progress to date for both methods. We also discuss challenges for viral delivery, including overcoming limited packaging capacity, immunogenicity associated with multiple dosing, and the potential for off-target effects, and nonviral delivery, including efforts to increase efficacy and to expand utility of nonviral carriers for use in extrahepatic tissues and cancer. Looking ahead, additional advances in the safety and efficiency of viral and nonviral delivery systems for tissue- and cell-type-specific gene editing will be required to enable broad clinical translation. We provide a summary of current delivery systems used for in vivo genome editing, organized with respect to route of administration, and highlight immediate opportunities for biomedical research and applications. Furthermore, we discuss current challenges for in vivo delivery of CRISPR/Cas9 systems to guide the development of future therapies.

HotSpotAnnotations-a database for hotspot mutations and annotations in cancer.

Hotspots, recurrently mutated DNA positions in cancer, are thought to be oncogenic drivers because random chance is unlikely and the knowledge of clear examples of oncogenic hotspots in genes like BRAF, IDH1, KRAS and NRAS among many other genes. Hotspots are attractive because provide opportunities for biomedical research and novel treatments. Nevertheless, recent evidence, such as DNA hairpins for APOBEC3A, suggests that a considerable fraction of hotspots seem to be passengers rather than drivers. To document hotspots, the database HotSpotsAnnotations is proposed. For this, a statistical model was implemented to detect putative hotspots, which was applied to TCGA cancer datasets covering 33 cancer types, 10 182 patients and 3 175 929 mutations. Then, genes and hotspots were annotated by two published methods (APOBEC3A hairpins and dN/dS ratio) that may inform and warn researchers about possible false functional hotspots. Moreover, manual annotation from users can be added and shared. From the 23 198 detected as possible hotspots, 4435 were selected after false discovery rate correction and minimum mutation count. From these, 305 were annotated as likely for APOBEC3A whereas 442 were annotated as unlikely. To date, this is the first database dedicated to annotating hotspots for possible false functional hotspots.

Carbon Nanomaterials and LED Irradiation as Antibacterial Strategies against Gram-Positive Multidrug-Resistant Pathogens.

Background: Due to current antibiotic resistance worldwide, there is an urgent need to find new alternative antibacterial approaches capable of dealing with multidrug-resistant pathogens. Most recent studies have demonstrated the antibacterial activity and non-cytotoxicity of carbon nanomaterials such as graphene oxide (GO) and carbon nanofibers (CNFs). On the other hand, light-emitting diodes (LEDs) have shown great potential in a wide range of biomedical applications. Methods: We investigated a nanotechnological strategy consisting of GO or CNFs combined with light-emitting diod (LED) irradiation as novel nanoweapons against two clinically relevant Gram-positive multidrug-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). The cytotoxicity of GO and CNFs was studied in the presence of human keratinocyte HaCaT cells. Results: GO or CNFs exhibited no cytotoxicity and high antibacterial activity in direct contact with MRSE and MRSA cells. Furthermore, when GO or CNFs were illuminated with LED light, the MRSE and MRSA cells lost viability. The rate of decrease in colony forming units from 0 to 3 h, measured per mL, increased to 98.5 ± 1.6% and 95.8 ± 1.4% for GO and 99.5 ± 0.6% and 99.7 ± 0.2% for CNFs. Conclusions: This combined antimicrobial approach opens up many biomedical research opportunities and provides an enhanced strategy for the prevention and treatment of Gram-positive multidrug-resistant infections.

Reactive jet impingement bioprinting of high cell density gels for bone microtissue fabrication

Advances in three-dimensional cell cultures offer new opportunities in biomedical research and drug development. However, there are still challenges to overcome, including the lack of reliability, repeatability and complexity of tissues obtained by these techniques. In this study, we describe a new bioprinting system called reactive jet impingement (ReJI) for the bioprinting of cell-laden hydrogels. Droplets of gel precursor solutions are jetted at one another such that they meet and react in mid-air before the gel droplets fall to the substrate. This technique offers a combination of deposition rate, cell density and cell viability which is not currently matched by any other bioprinting technique. The importance of cell density is demonstrated in the development of bone microtissues derived from immortalised human bone marrow stem cells. The cells were printed with high viability within a collagen-alginate-fibrin gel, and tissue specific gene expression shows significantly higher tissue maturation rates using the ability of the ReJI system to deposit gels with a high cell density.

In vivo label-free confocal imaging of the deep mouse brain with long-wavelength illumination.

Optical microscopy is a valuable tool for in vivo monitoring of biological structures and functions because of its non-invasiveness. However, imaging deep into biological tissues is challenging due to the scattering and absorption of light. Previous research has shown that 1300 nm and 1700 nm are the two best wavelength windows for deep brain imaging. Here, we combined long-wavelength illumination of ~1700 nm with reflectance confocal microscopy and achieved an imaging depth of ~1.3 mm with ~1-micrometer spatial resolution in adult mouse brains, which is 3-4 times deeper than that of conventional confocal microscopy using visible wavelength. We showed that the method can be added to any laser-scanning microscopy with simple and low-cost sources and detectors, such as continuous-wave diode lasers and InGaAs photodiodes. The long-wavelength, reflectance confocal imaging we demonstrated is label-free, and requires low illumination power. Furthermore, the imaging system is simple and low-cost, potentially creating new opportunities for biomedical research and clinical applications.

Unexplored therapeutic opportunities in the human genome.

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

From Nonclinical Research to Clinical Trials and Patient-registries: Challenges and Opportunities in Biomedical Research

The most important challenge faced by human beings is health. The only way to provide better solutions for health care is innovation, true innovation. The only source of true innovation is research, good research indeed. The pathway from a basic science study to a randomized clinical trial is long and not free of bumps and even landmines. These are all the obstacles and barriers that limit the availability of resources, entangle administrative-regulatory processes, and restrain investigators’ initiatives. There is increasing demand for evidence to guide clinical practice but, paradoxically, biomedical research has become increasingly complex, expensive, and difficult to integrate into clinical care with increased barriers to performing the practical aspects of investigation. We face the challenge of increasing the volume of biomedical research and simultaneously improving the efficiency and output of this research. In this article, we review the main stages and methods of biomedical research, from nonclinical studies with animal and computational models to randomized trials and clinical registries, focusing on their limitations and challenges, but also providing alternative solutions to overcome them. Fortunately, challenges are always opportunities in disguise.

Poly(HDDA)-Based Polymers for Microfabrication and Mechanobiology

ABSTRACTMaterials processing and additive manufacturing afford exciting opportunities in biomedical research, including the study of cell-material interactions. However, some of the most efficient materials for microfabrication are not wholly suitable for biological applications, require extensive post-processing or exhibit high mechanical stiffness that limits the range of applications. Conversely, materials exhibiting high cytocompatibility and low stiffness require long processing times with typically decreased spatial resolution of features. Here, we investigated the use of hexanediol diacrylate (HDDA), a classic and efficient polymer for stereolithography, for oligodendrocyte progenitor cell (OPC) culture. We developed composite HDDA-polyethylene glycol acrylate hydrogels that exhibited high biocompatibility, mechanical stiffness in the range of muscle tissue, and high printing efficiency at ∼5 μm resolution.

Lessons Learned from the Broadening Experiences in Scientific Training (BEST) Awards

Success of the entire biomedical research enterprise relies on the creativity, innovation, and dedication of the scientific workforce. There is ongoing concern that the long training time and the declining percentage of PhD graduates that obtain independent academic research positions are making biomedical research a less attractive career. Additionally, although many graduates are moving into essential research‐related occupations rather than research‐intensive positions, many current training programs do little to prepare trainees for these other career options. The NIH is committed to supporting a sustainable and robust workforce equipped to address the greatest challenges and opportunities in biomedical research, recognizing that traditional research‐intensive positions are not the only means by which PhD graduates can meaningfully contribute to the biomedical research enterprise. To address this need and based on recommendations from the Advisory Committee to the Director (ACD) Working Group on Biomedical Workforce, the NIH Common Fund launched the “Strengthening the Biomedical Research Workforce” program as one component of a trans‐NIH strategy to enhance training opportunities for early career scientists to better prepare them for a variety of career options in the dynamic biomedical workforce landscape.These awards, also called the Broadening Experiences in Scientific Training (BEST) awards, are providing support for institutions to develop innovative approaches to complement traditional research training in biomedical sciences. Institutions are encouraged to partner with industry or other entities to provide a wealth of diverse training opportunities for their trainees, and the awardees have formed a network to share experiences and determine best practices. One of the novelties of this program is the NIH cross‐site evaluation of all the programs. The desired impacts of the program include: 1) enhancing trainee agency to make career decisions, 2) reduced time to desired, non‐training, non‐terminal career opportunities and reduced time in postdoctoral positions, and 3) the creation and/or further development of institutional infrastructure to continue the BEST‐like activities. This rigorous analysis will assess impact at the home institutions, and proven approaches will be widely disseminated throughout the training community.Support or Funding InformationThese awards are supported by the NIH Common Fund.

Ethical considerations for informed consent in infertility research: The use of electronic health records.

The growing use of electronic health records (EHRs) in healthcare provides rich opportunities for biomedical research. Using EHRs, massive quantities of patient data can be extracted for research without the need to recruit patients, schedule study visits, or rely on self-reporting. However, this innovation poses significant concerns about patient privacy and confidentiality of data. Patients receiving infertility treatment may be particularly vulnerable to data breaches, as their EHRs often include sensitive health information about themselves, their partner, and their offspring. Helping patients with infertility to make informed decisions about sharing data is crucial, yet little is known about best practices for obtaining informed consent to use EHR data for research. This commentary reviews possible options for obtaining informed consent for EHR use among patients seeking fertility services. In addition, this commentary summarizes the limited research available on patient preferences for informed consent practices.