Medical Research Research Articles

GLP-1 for Treating Obesity—Origin, History, and Evolution

In this Viewpoint, 2024 Lasker-DeBakey Clinical Medical Research Award winner Lotte Bjerre Knudsen describes her discovery of glucagon-like peptide-1 for the treatment of patients with obesity.

Hunting down the elusive cytosolic-DNA sensor

The 2024 Albert Lasker Basic Medical Research Award was attributed to Zhijian (James) Chen for “the discovery of the cGAS enzyme that senses foreign and self DNA, solving the mystery of how DNA stimulates immune and inflammatory responses.” Bringing to bear an ingenious in vitro complementation system, an astute insight, and superlative biochemistry, Chen and colleagues identified cGAS (cGAMP synthase) as both the molecule that perceives cytosolic DNA in infected, stressed, or dying cells and the enzyme that catalyzes the synthesis of cGAMP (cyclic GMP-AMP), a critical second messenger along the route to inflammatory cytokine production. These findings cleared up the reigning confusion surrounding a major mechanism of inciting the innate immune system, with therapeutic implications for fighting infections, containing tumors, and extinguishing autoimmune and inflammatory diseases.

Understanding chromoblastomycosis in Sri Lanka; insights into fungal aetiology and antifungal susceptibility patterns

Introduction: Chromoblastomycosis is a chronic disfiguring fungal infection of the subcutaneous tissue found mainly in the socio-economically marginalized population in the tropical and sub-tropical regions, characterized by the presence of sclerotic cells. This study was done with the aim of identifying the antifungal sensitivity patterns of the causative agents of chromoblastomycosis in Sri Lanka from 1992 to 2019.Methodology: Study was done on the stored isolates received from patients with chromoblastomycosis since 1992 to 2019, to the Mycology Reference Laboratory of Medical Research Institute, Colombo. Isolates were revived by subculture on Potato dextrose agar. Identification was done phenotypically. Antifungal sensitivity testing was performed by E test method. Available demographic and clinical data were analysed.Results: Of the 74 isolates, 71 (96%) were caused by Fonsecaea pedrosoi. Mean MIC for the antifungals tested were lowest for posaconazole 0.015 μg/ml followed by itraconazole 0.225 μg/ml, and voriconazole 0.768 μg/ml while amphotericin B demonstrated complete resistance with mean MIC of 30.591 μg/ml. No statistically significant differences were noted on the antifungal sensitivity of the isolates from 1992 to 2004 and 2005 to 2019.Conclusions: Fonsecaea pedrosoi was the commonest causative agent causing chromoblastomycosis in the studied population. Posaconazole demonstrated the lowest MIC values for the tested isolates followed by itraconazole and voriconazole. Amphotericin B demonstrated very high MIC values which were likely to result in clinical failure upon treatment. MIC values demonstrated minimal fluctuations throughout the tested time.

Temporal restriction of biomedical research on human embryos created in vitro

The article is devoted to the study of temporal limitation of biomedical research ofhuman embryos created in vitro. The author has investigated various models of settingtemporal restrictions, in particular, the most widespread in the world model of 14 daystemporal limitation. The article examines the validity of various models of temporal limitations(in particular, models that provide for temporal limitation of 7 days, 14 days, 28days) and their ability to maintain a balance between protection of a human embryo, interestsof a human, society, state, and science.Having studied the practice of establishing temporal limitations in various countries,including Switzerland, the Czech Republic, the United Kingdom, and the Netherlands, theauthor reached a conclusion. The research focused on issues related to the status of thehuman embryo and the scientific potential of studying embryos created in vitro more than14 days since their creation. The author concluded that the existing models, particularlythe 14-day rule, do not maintain a balance of interests. Therefore, it is necessary to establisha model that provides for multiple temporal limitations. The author has proposed atwo-level model of temporal limitation. The first level provides for the possibility of cultivatinga human embryo created in vitro up to the 14th day of its development from themoment of creation and carrying out biomedical research of such embryos up to the 14thday of their development from the moment of creation. The second level, which in exceptionalcases and in the presence of stricter conditions provides for the possibility of cultivatinga human embryo created in vitro up to the 28th day of its development from themoment of creation and carrying out biomedical research of such embryos up to the 28thday of their development from the moment of creation. Such a model is a compromise andwill ensure the balance between proper protection of a human embryo and interests of aperson, society, state, and science.

A Subtractive Method to Chemically Pattern Liquid Metal for Stretchable Circuits

AbstractAdvancements in biomedical research have spurred the development of stretchable electronic devices. While soft insulators are readily available, soft conductors with metal‐like electrical conductivity are rare. Gallium and its alloys, being nontoxic and intrinsically stretchable, are potentially ideal solutions. However, current additive liquid metal (LM) patterning methods face limitations in achieving high‐throughput, high‐resolution, and high‐density LM wiring. Here, a subtractive LM patterning method is developed to meet all these requirements simultaneously. The innovative method involves parallel filling a single continuous microfluidic mesh network with LM that short‐circuits all the pins and pads of a circuit, followed by parallel cutting of the unwanted short‐circuited interconnections using hydrochloric acid (HCl) vapor. Cutting locations are pre‐defined by designing narrower intersecting channels, leveraging capillary force for precise filling and cutting. The process is characterized using a multidimensional parametric study with varying LM line widths and HCl concentrations, and in situ impedance measurements to assess insulation performance. To showcase its high‐throughput capabilities, a mock circuit is used to successfully generate complex LM interconnects that connected hundreds of electrical pads. Finally, a stretchable LM circuit with a micro‐LED array is fabricated to demonstrate the practical application of this technology for massively parallel wiring in stretchable electronics.

Comparative performance analysis of large language models: ChatGPT-3.5, ChatGPT-4 and Google Gemini in glucocorticoid-induced osteoporosis

BackgroundsThe use of large language models (LLMs) in medicine can help physicians improve the quality and effectiveness of health care by increasing the efficiency of medical information management, patient care, medical research, and clinical decision-making.MethodsWe collected 34 frequently asked questions about glucocorticoid-induced osteoporosis (GIOP), covering topics related to the disease’s clinical manifestations, pathogenesis, diagnosis, treatment, prevention, and risk factors. We also generated 25 questions based on the 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (2022 ACR-GIOP Guideline). Each question was posed to the LLM (ChatGPT-3.5, ChatGPT-4, and Google Gemini), and three senior orthopedic surgeons independently rated the responses generated by the LLMs. Three senior orthopedic surgeons independently rated the answers based on responses ranging between 1 and 4 points. A total score (TS) > 9 indicated ‘good’ responses, 6 ≤ TS ≤ 9 indicated ‘moderate’ responses, and TS < 6 indicated ‘poor’ responses.ResultsIn response to the general questions related to GIOP and the 2022 ACR-GIOP Guidelines, Google Gemini provided more concise answers than the other LLMs. In terms of pathogenesis, ChatGPT-4 had significantly higher total scores (TSs) than ChatGPT-3.5. The TSs for answering questions related to the 2022 ACR-GIOP Guideline by ChatGPT-4 were significantly higher than those for Google Gemini. ChatGPT-3.5 and ChatGPT-4 had significantly higher self-corrected TSs than pre-corrected TSs, while Google Gemini self-corrected for responses that were not significantly different than before.ConclusionsOur study showed that Google Gemini provides more concise and intuitive responses than ChatGPT-3.5 and ChatGPT-4. ChatGPT-4 performed significantly better than ChatGPT3.5 and Google Gemini in terms of answering general questions about GIOP and the 2022 ACR-GIOP Guidelines. ChatGPT3.5 and ChatGPT-4 self-corrected better than Google Gemini.

A national-wide survey on clinical implementation of PGx testing into precision therapeutics for Chinese children: a long way before standard clinical practice

BackgroundPharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China.MethodsA survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made.ResultsQuestionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost.ConclusionAlthough GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

Japanese Perception of Brain Death and Implications for New Medical Technologies: Quantitative and Qualitative Social Media Analysis.

Brain death has been used to decide whether to keep sustained care and treatment. It can facilitate tissue, organ, and body donation for several purposes, such as transplantation and medical education and research. In Japan, brain death has strict diagnostic criteria and family consent is crucial, but it has been a challenging concept for the public since its introduction, including knowledge and communication issues. We analyzed data across YouTube and Twitter in Japan to uncover actors and assess the quality of brain death communication, providing recommendations to communicate new medical technologies. Using the keyword "" (brain death), we collected recent data from YouTube and Twitter, classifying the data into 5 dimensions: time, individuality (type of users), place, activity, and relations (hyperlinks). We employed a scale to evaluate brain death information quality. We divided YouTube videos into 3 groups and assessed their differences through statistical analysis. We also provided a text-based analysis of brain death-related narratives. Most videos (20/61, 33%) were uploaded in 2019, while 10,892 tweets peaked between July 3 and 9, 2023, and June 12 and 18, 2023. Videos about brain death were mostly uploaded by citizens (18/61, 27%), followed by media (13/61, 20%) and unknown actors (10/61, 15%). On the other hand, most identified users in a random sample of 100 tweets were citizens (73/100, 73%), and the top 10 retweeted and liked tweets were also mostly authored by citizens (75/100, 75%). No specific information on location was uncovered. Information videos contained guides for accreditation of the National Nursing Exam and religious points of view, while misinformation videos mostly contained promotions by spirituality actors and webtoon artists. Some tweets involved heart transplantation and patient narratives. Most hyperlinks pointed to YouTube and Twitter. Brain death has become a common topic in everyday life, with some actors disseminating high-quality information, others disseminating no medical information, and others disseminating misinformation. Recommendations include partnering with interested actors, discussing medical information in detail, and teaching people to recognize pseudoscience.

Single Cell Sequencing and Spatial Transcriptomics in Kidney Transplantation

Abstract Purpose of Review Progress in biology and medicine relies on technological advances. The ability to examine gene expression from single cells in tissues with complex architecture is now possible with the advent of single cell sequencing and spatial transcriptomics methods. This review will outline how these methods have been applied to kidney transplantation and their inherent challenges and limitations. Recent Findings The transcriptomes of single cells can now be defined in health and disease allowing for the differences to be investigated. Advanced in situ sequencing and capture methodologies now add spatial resolution to single cell transcriptomics. However, such powerful methods bring challenges, most notably the associated computational burden that is required to make the resulting high-dimensional output data interpretable. A second challenge is that of cost. Thankfully, as with many new technologies’ costs will drop over time making these methods available to more research groups. Summary The sequencing and analysis of gene expression at the single cell level with spatial information retained is now feasible. These methods are major advances for biomedical research and bring huge potential with regards to the better understanding of disease at cellular and organ levels.

Poly(vinylpyrrolidone)-Enhanced CRISPR-Cas System for Robust Nucleic Acid Diagnostics.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology has opened a new path for molecular diagnostics based on RNA programmed trans-cleavage activity. However, their accessibility for highly sensitive clinical diagnostics remains insufficient. In this study, we systematically investigated the impact of various surfactants on the CRISPR-Cas12a system and found that poly(vinylpyrrolidone) (PVP), a nonionic surfactant, showed the highest enhancement effect among these tested surfactants. Additionally, the enhancement effects of PVP are compatible and versatile to CRISPR-Cas12b and Cas13a systems, improving the sensitivity of these CRISPR-Cas systems toward synthetic targets by 1-2 orders of magnitude. By integrating the PVP-enhanced CRISPR system with isothermal nucleic acid amplification, both the two- and one-step assays exhibited comparable sensitivity and specificity to gold-standard quantitative polymerase chain reaction (qPCR) in the assay of clinical human papillomavirus (HPV) samples, thereby holding significant promise for advancing clinical diagnostics and biomedical research.

4-Halomethyl-Substituted Imidazolium Salts: a Versatile Platform for the Synthesis of Functionalized NHC Precursors.

N,N'-Diarylimidazolium salts containing haloalkyl functional groups that are reactive with various nucleophiles are considered to be promising reagents for the preparation of functionalized N-heterocyclic carbene (NHC) ligands, which are in demand in catalysis, materials science, and biomedical research. Recently, 4-chloromethyl-functionalized N,N'-diarylimidazolium salts became readily available via the condensation of N,N'-diaryl-2-methyl-1,4-diaza-1,3-butadienes with ethyl orthoformate and Me3SiCl, but these compounds were found to have insufficient reactivity in reactions with many nucleophiles. These chloromethyl salts were studied as precursors in the synthesis of bromo- and iodomethyl-functionalized imidazolium salts by halide anion exchange. The 4-ICH2-functionalized products were found to be unstable, whereas a series of novel 4-bromomethyl functionalized N,N'-diarylimidazolium salts were obtained in good yields. These bromomethyl-functionalized imidazolium salts were found to be significantly more reactive towards various N, O and S nucleophiles than the chloromethyl counterparts and enabled the preparation of previously inaccessible heteroatom-functionalized imidazolium salts, some of which were successfully used as NHC proligands in the preparation of Pd/NHC and Au/NHC complexes.

Wasserstein-Kaplan-Meier Survival Regression

Survival analysis plays a pivotal role in medical research, offering valuable insights into the timing of events such as survival time. One common challenge in survival analysis is the necessity to adjust the survival function to account for additional factors, such as age, gender, and ethnicity. We propose an innovative regression model for right-censored survival data across heterogeneous populations, leveraging the Wasserstein space of probability measures. Our approach models the probability measure of survival time and the corresponding non-parametric Kaplan-Meier estimator for each subgroup as elements of the Wasserstein space. The Wasserstein space provides a flexible framework for modeling heterogeneous populations, allowing us to capture complex relationships between covariates and survival times. We address an underexplored aspect by deriving the non-asymptotic convergence rate of the Kaplan-Meier estimator to the underlying probability measure in terms of the Wasserstein metric. The proposed model is supported with a solid theoretical foundation including pointwise and uniform convergence rates, along with an efficient algorithm for model fitting. The proposed model effectively accommodates random variation that may exist in the probability measures across different subgroups, demonstrating superior performance in both simulations and two case studies compared to the Cox proportional hazards model and other alternative models.

Квантовые вычисления в медицинской физике: особенности алгоритмов и их перспективы

Background: Quantum computing represents a paradigm leap in computational capabilities, with potential applications across various scientific disciplines. The complicated computations required for imaging, radiation therapy, and molecular modeling in medical physics give novel prospects for quantum computing. Objective: This article investigates the role of quantum computing in medical physics research, with an emphasis on its potential to improve computational efficiency and accuracy and develop novel treatment approaches. Methods: A thorough literature analysis was undertaken to investigate recent advances in quantum computing and their implications in medical physics. Case studies were reviewed to demonstrate practical applications and possible advantages. Theoretical models were tested to forecast future developments. Statistical data from quantum computing implementations were gathered from many sources, particularly on improving processing speed and accuracy in medical physics applications. Results: The findings show that quantum computing can significantly improve the processing speed of complex simulations and imaging techniques, with some quantum algorithms outperforming classical algorithms by up to 100 times. In radiation therapy planning, quantum computing has exhibited a 25% boost in dose distribution calculation precision. Quantum algorithms have lowered calculation times in molecular modeling by about 40%, potentially boosting drug development and customized therapy by 30%. Conclusion: Quantum computing has the potential to alter medical physics by increasing computational capacity, which could lead to advancements in diagnostics, treatment planning, and medication development. The statistical results corroborate the promise of quantum computing in these domains, emphasizing the importance of ongoing interdisciplinary collaboration and research to fully achieve these benefits and address present hurdles in incorporating quantum computing into clinical practice.

Quantitative proteomics of patient fibroblasts reveal biomarkers and diagnostic signatures of mitochondrial disease.

Mitochondrial diseases belong to the group of inborn errors of metabolism (IEM), with a prevalence of 1:2,000-1:5,000. They are the most common form of IEM, but despite advances in next-generation sequencing technologies, almost half of the patients are left genetically undiagnosed. We investigated a cohort of 61 patients with defined mitochondrial disease to improve diagnostics, identify biomarkers, and correlate metabolic pathways to specific disease groups. Clinical presentations were structured using human phenotype ontology terms, and mass spectrometry-based proteomics was performed on primary fibroblasts. Additionally, we integrated six patients carrying variants of uncertain significance (VUS) to test proteomics as a diagnostic expansion. Proteomic profiles from patient samples could be classified according to their biochemical and genetic characteristics, with the expression of five proteins (GPX4, MORF4L1, MOXD1, MSRA and TMED9) correlating with the disease cohort, and thus, acting as putative biomarkers. Pathway analysis showed a deregulation of inflammatory and mitochondrial stress responses. This included the upregulation of glycosphingolipid metabolism and mitochondrial protein import, as well as the downregulation of arachidonic acid metabolism. Furthermore, we could assign pathogenicity to a VUS in MRPS23 by demonstrating the loss of associated mitochondrial ribosome subunits. We established mass spectrometry-based proteomics on patient fibroblasts as a viable and versatile tool for diagnosing patients with mitochondrial disease. The NovoNordisk Foundation, Knut and Alice Wallenberg Foundation, Wellcome Centre for Mitochondrial Research, UK Medical Research Council, and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children.

Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.

Trends and insights in animal and biomedical research: A 5-year scientometric analysis of orthodontic peer-reviewed journals

Biomedical research plays a critical role in advancing orthodontic innovations by identifying new targets for therapeutic interventions and developing more effective, personalized orthodontic treatment. This study evaluates the major contributors and trends in animal-related orthodontic research over the past 5 years (2017-2023). All animal-related studies published in the eight orthodontic journals listed in the 2022 Journal Citation Reports between January 2017 and June 2023 were retrieved from the Web of Science Core Collection. After examination, the following bibliometric data were extracted from each article: title, authors, affiliations, geographic origin, year of publication, journal name, and keywords. Multiple bibliometric software packages including Biblioshiny R-package software, Datawrapper, and Datasmith were used to analyze different bibliometric outcomes. A total of 3669 articles were screened from which 266 were selected and included in the analysis. The annual growth rate of production exhibited a decline of 11.18%. Most of the included studies focused on orthodontic tooth movement (32.3%), mainly utilizing rat models (50%). Although the United States accounted for the highest number of publications (n = 236), the trend in funded research showed a decreasing trajectory over time, with notably limited funding from the National Institutes of Health. This study reveals a declining trend in overall animal-related orthodontic research, highlighted by a significant decrease in National Institutes of Health funding over time. To address this gap, academic institutions and professional organizations should support initiatives fostering biomedical orthodontic research.

Exosome Loaded Protein Hydrogel for Enhanced Gelation Kinetics and Wound Healing.

Exosomes are being increasingly explored in biomedical research for wound healing applications. Exosomes can improve blood circulation and endocrine signaling, resulting in enhanced cell regeneration. However, exosome treatments suffer from low retention and bioavailability of exosomes at the wound site. Hydrogels are a popular tool for drug delivery due to their ability to encapsulate drugs in their network and allow for targeted release. Recently, hydrogels have proven to be an effective method to provide increased rates of wound healing when combined with exosomes that can be applied noninvasively. We have designed a series of single-domain protein-based hydrogels capable of physical cross-linking and upper critical solution temperature (UCST) behavior. Hydrogel variant Q5, previously designed with improved UCST behavior and a significantly enhanced gelation rate, is selected as a candidate for encapsulation release of exosomes dubbed Q5Exo. Q5Exo exhibits low critical gelation times and significant decreases in wound healing times in a diabetic mouse wound model showing promise as an exosome-based drug delivery tool and for future hybrid, noninvasive protein-exosome design.

Institutional care and education: circulation of knowledge about epilepsy in Sweden 1915-40.

This article focuses on the circulation of knowledge about epilepsy in Sweden between 1915 and 1940. During the period medical research on epilepsy increased, which simultaneously brought a new degree of specialisation and distinction between branches of medicine. The aim of this article is to study the impact of new medical knowledge about epilepsy on the treatment and education of children with epilepsy in Sweden. In order to concretise the aim, the study focuses on the asylum Margarethahemmet. The key source material consists of Margarethahemmet's annual reports and yearbooks. The minutes of the meetings of the Swedish General Association for the Care of the Feebleminded and Epileptic for the period 1915-1938 have been used as supplementary material. In order to trace the impact of medical discoveries on Margarethahemmet's operations, contemporary scientific articles, mostly from Germany, have also been used. The article demonstrates how new research and new knowledge was sought internationally and nationally, to provide doctors and special teachers at the asylum with a proper knowledge about education, care and treatment for children with epilepsy. The increased understanding of the disease directly impacted the ability of a stigmatized group - people with epileptic disorder - to actively participate in society on the same terms as others.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK

IntroductionPreterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the...

Evolution and applications of CRISPR-Cas9 technology in last decade

CRISPR-Cas9 technology has rapidly evolved and expanded its applications since its inception in 2015. This research paper provides a comprehensive overview of the advancements and applications of CRISPR-Cas9 technology from 2015 to 2023. We review key milestones in CRISPR-Cas9 research, including improvements in genome editing efficiency, novel applications in gene therapy and biotechnology, and emerging trends in CRISPR-based diagnostics and therapeutics. Additionally, we discuss the ethical considerations, regulatory challenges, and future prospects of CRISPR-Cas9 technology. Through a thorough analysis of the literature spanning nearly a decade, this paper aims to highlight the transformative impact of CRISPR-Cas9 technology on biomedical research and its potential for addressing pressing societal challenges.