Enabling Demonstrated Consent for Biobanking with Blockchain and Generative AI.

Participation in research is supposed to be voluntary and informed. Yet it is difficult to ensure people are adequately informed about the potential uses of their biological materials when they donate samples for future research. We propose a novel consent framework which we call "demonstrated consent" that leverages blockchain technology and generative AI to address this problem. In a demonstrated consent model, each donated sample is associated with a unique non-fungible token (NFT) on a blockchain, which records in its metadata information about the planned and past uses of the sample in research, and is updated with each use of the sample. This information is accessible to a large language model (LLM) customized to present this information in an understandable and interactive manner. Thus, our model uses blockchain and generative AI technologies to track, make available, and explain information regarding planned and past uses of donated samples.

The impact of sex/gender-specific funding and editorial policies on biomedical research outcomes: a cross-national analysis (2000-2021).

Reflecting sex and gender characteristics in biomedical research is critical to improving health outcomes and reducing adverse effects from medical treatments. This study investigates the impact of sex/gender-specific funding policies and journal editorial standards on the integration of sex/gender analysis in biomedical research publications. Using data from the United States, Canada, the United Kingdom, and other countries between 2000 and 2021, we assessed how these policies influenced research output in the fields of medicine and life sciences. Our findings show that countries with progressive funding policies and journals promoting sex/gender-based reporting have significantly improved research quality and publication rates. This highlights the importance of coordinated policy efforts and editorial practices in advancing integrated sex/gender research. We recommend continued global efforts from policymakers, funding bodies, and journals to embed sex/gender perspectives in scientific inquiry, ensuring more effective and equitable biomedical advancements.

EXPRESS: Combined treatment with ruxolitinib and MK-2206 inhibits ERα activity by inhibiting MAPK signaling in BT474 breast cancer cells.

Triple-positive breast cancer (TPBC) is a type of breast cancer that overexpresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Dysregulation of estrogen receptor signaling has been implicated in the pathogenesis of breast cancer. ERα activation triggers the production of second messengers, including cAMP, leading to the activation of signals such as PI3K/AKT or Ras/MAPK. Ruxolitinib is a specific inhibitor of JAK1/JAK2. MK-2206 is an allosteric inhibitor of the Akt. The limitations of the use of ruxolitinib and MK-2206 as single agents necessitate the development of combination therapies with other drugs. This study is the first to investigate the effects of combining ruxolitinib with MK-2206 on MAPK and PI3K/AKT signaling in BT474 breast cancer cells. Additionally, this work aimed to increase the anticancer effects of cotreatment with MK-2206 and ruxolitinib. Ruxolitinib, MK-2206, and their combination reduced cell viability in a dose- and time-dependent manner, as determined by MTT assays after 48 hours of treatment. Colony formation and wound healing assays demonstrated that MK-2206 exhibited a synergistic anti-proliferative effect. The effects of ruxolitinib, MK-2206, and their combination on PI3K/AKT and MAPK signaling were assessed via western blotting. Ruxolitinib and MK-2206 combined treatment inhibits cell death in BT474 cells by downregulating ERα, Src-1, ERK1/2, SAPK/JNK, and c-Jun. Our results revealed the relationships among the ERα, PI3K/AKT, and MAPK signaling pathways in ER+ breast cancer cells. Understanding the interactions among ERα, PI3K-AKT-mTOR, and MAPK could lead to novel combination therapies.

Beyond Bias: Aggregate Approaches to Conflicts of Interest Research and Policy in Biomedical Research.

Considerable efforts have been devoted to addressing the problem of conflicts of interest (COI) in health research, policy, education, and practice. An overwhelming body of evidence demonstrates that conflicts associate with deleterious outcomes for the biomedical research enterprise. Nevertheless, little has changed for research, specifically, since the Institute of Medicine's landmark Conflicts of Interest in Medical Research, Practice, and Education was published over a decade ago. In this article, we draw on interdisciplinary research on manufactured controversies in science-policy deliberation to argue that the development of meaningful COI policy has been stymied through argumentative "wedges" designed to delay consensus and policy formation. Argumentative wedges disrupt policy formation by mischaracterizing the evidence base, continuously redefining the terms of the debate and/or recommending overly narrow criteria for who should be allowed to participate in policy deliberation. In this article, we argue researchers and policymakers interested in better addressing the harmful effects of COI can improve their efforts through strategic efforts designed to disrupt the wedges of manufactured controversy. Additionally, we argue that efforts to address COI can be further enhanced through embracing a broader framework for COI inquiry. Specifically, we argue that aggregate approaches to COI can help to disrupt these wedges and provide a strong foundation for future policy.

Paradigm Shift: Outcomes from a Physician-Scientist Undergraduate Pipeline Program.

Diverse medical and research teams are essential to culturally-responsive care and robust progress of biomedical research. However, structural inequities stymie the entry of trainees from underrepresented in medicine (URiM) backgrounds into the physician-scientist pipeline. The Preparation for Graduate and Medical Education (PARAdiGM) program was designed to provide students from underrepresented backgrounds early exposure to physician-scientist training in the context of ample mentorship and programmatic support. By emphasizing research experience, career exposure, presentation skills, mentorship, and application assistance, PARAdiGM is an incipient experience priming this student group to pursue careers in academic medicine. Since its establishment in 2014, PARAdiGM is already increasing entry of URiM students into the physician-scientist pipeline. Encouragingly, the majority of PARAdiGM alumni have matriculated into US medical schools, of which 16% are currently enrolled in MD-PhD programs. Early outcomes from PARAdiGM suggest that an immersive framework, longitudinal mentoring, and opportunity for self-growth should be incorporated into URiM pipeline programs on a larger scale. In these ways, helping students to envision themselves as members of the physician-scientist community is a step toward breaking down the barriers currently limiting URiM entry into academic medicine.

Standing strong: War-related challenges in Ukrainian biomedical research and opportunities for support.

The prolonged war in Ukraine is having a strong impact on all sectors of the Ukrainian society, including biomedical research. Although the material and psychological conditions are challenging, the country and its researchers are courageously managing to continue their activities. This perspective paper describes the multiple challenges faced by Ukrainian biomedical researchers during wartime and outlines strategies to support and enhance collaboration with the global scientific community. Ukraine has a rich scientific history and modern expertise in biomedical research, and developing more international collaborations with Ukraine can have mutual benefits for all involved parties.

Ethics Review of Biomedical Research in Uzbekistan: Policy and Program Gaps.

We describe the national health research ethics review system of Uzbekistan and identify policy and program gaps that impede the protection of human research subjects. We find that the National Ethic Committee (NEC), functioning at the national level, is solely responsible for conducting research ethics review. There is little evidence that regional ethics committees work as intended, and there is no research ethics review at medical institutes and research centers even though they conduct CDTs (clinical drug trials). There is no national policy for the ethical review of non-clinical trials. We recommend the establishment of institutional review boards (IRBs) at medical institutes and research centers while at the same time building capacity at the national level to oversee and support the research ethics review system of the entire country.

Case Study of Severe Accidental Hypothermia with Rapid Cooling, Preserved Shivering, and Consciousness with a Summary of Similar Case Reports.

We describe a case of severe accidental hypothermia of a kayaker with preserved consciousness and shivering despite a rectal temperature of 22.9°C following a 50-min immersion in 3°C water with an estimated core temperature cooling rate of 10.6°C/h. Based on survival at sea prediction curves and cooling rates from physiology studies, cold water (eg, 0-5°C) immersion is expected to drop core temperature by 2 to 4°C/h. Furthermore, accidental hypothermia classification systems predict that severely hypothermic patients are usually unconscious and not shivering. The patient in this report rewarmed rapidly at 3.6°C/h with only minimally invasive measures and was discharged fully neurologically intact. In 41 similar cases of survival in moderate to severe hypothermia with core temperatures <32°C due to cold water immersion, cold air exposure, or avalanche burial, mean cooling rates were 4.3±3.3°C/h (range 0.4-10.6°C/h). Including the current patient, shivering was reported in only four cases. We found several other cases of rewarming from moderate to severe hypothermia with only minimally invasive measures. The current and summarized cases lead us to conclude that patients may be at risk of severe hypothermia in <60 min of cold water immersion and that it is possible for severely hypothermic patients to have preserved consciousness, close to normal vital signs, and shivering. Minimally invasive or noninvasive rewarming of patients with severe hypothermia is also possible, especially in those who continue to shiver. Hypothermia management should not necessarily be guided by classification systems or core temperature alone but rather by a careful consideration of the entire clinical picture.

Accelerating covalent binding studies: Direct mass shift measurement with acoustic ejection and TOF-MS.

Tracking chemical reactions by measuring incurred mass shifts upon successful binding is a direct and attractive alternative to existing assays based on chemical tags. Traditional methods use liquid chromatography-mass spectrometry (LC-MS), and because the required buffers are not amenable to direct MS injection, sample pre-treatment is needed to desalt. This leads to analysis times from ten seconds to minutes per sample, limiting throughput and preventing widespread application. Combining an acoustic ejection (AE) interface with a time-of-flight mass spectrometer (MS) removes this bottleneck, as samples can be directly introduced at rates of up to one second per sample. This article describes a complete workflow for measuring the covalent binding of compounds to proteins in real-time, from assay to data evaluation. It is noteworthy that this is the first instance of using SCIEX Echo® MS+ system with ZenoTOF 7600 system to study the kinetic regimes of covalent binding.

Yellapragada Subbarow: A Pioneer in Biomedical Research and the Unsung Hero of Modern Medicine.

Yellapragada Subbarow, an often overlooked yet monumental figure in biomedical research, made groundbreaking contributions that have profoundly shaped modern medicine. Born in 1895 in Andhra Pradesh, India, Subbarow's journey from humble beginnings to a pioneering biochemist is a testament to his relentless determination and intellectual prowess. His discoveries, including the elucidation of adenosine triphosphate (ATP), the development of folic acid, and the introduction of methotrexate and tetracycline antibiotics, have had a lasting impact on various fields such as biochemistry, oncology, and infectious disease treatment. Despite his significant scientific achievements, Subbarow's name remains relatively obscure outside academic circles. This review highlights his pivotal contributions and explores the reasons behind his underrecognition. By examining his life's work, this article seeks to celebrate Subbarow's enduring legacy and advocate for greater recognition of his contributions to medical science. His story enriches our understanding of scientific progress and is an inspiring example of the profound impact of perseverance and innovation in advancing human health. Through this review, we hope to honor Subbarow's remarkable achievements and bring deserved attention to one of the unsung heroes of modern medicine.

Innovation at the Interface between Academia and Industry: The BioMed X Model.

In the evolving landscape of biomedical research, the convergence of molecular biology and translational medicine has ushered in a new era of pharmaceutical innovation. This paradigm shift, characterized by significant advances in targeted therapies and gene editing, emphasizes the critical role of integrating academic research - and academic researchers - within industry settings. Contemporary innovation models are moving beyond traditional, corporation-centered frameworks, adopting more open, collaborative approaches. Here, we discuss the challenges and solutions brought about by this new direction in pharma innovation and describe the BioMed X innovation model, a unique open innovation approach that has been growing continuously over the past ten years.

Applying the Atomic Force Microscopy Technique in Medical Sciences-A Narrative Review.

Penetrating deep into the cells of the human body in real time has become increasingly possible with the implementation of modern technologies in medicine. Atomic force microscopy (AFM) enables the effective live imaging of cellular and molecular structures of biological samples (such as cells surfaces, components of biological membranes, cell nuclei, actin networks, proteins, and DNA) and provides three-dimensional surface visualization (in X-, Y-, and Z-planes). Furthermore, the AFM technique enables the study of the mechanical, electrical, and magnetic properties of cells and cell organelles and the measurements of interaction forces between biomolecules. The technique has found wide application in cancer research. With the use of AFM, it is not only possible to differentiate between healthy and cancerous cells, but also to distinguish between the stages of cancerous conditions. For many years, AFM has been an important tool for the study of neurodegenerative diseases associated with the deposition of peptide amyloid plaques. In recent years, a significant amount of research has been conducted on the application of AFM in the evaluation of connective tissue cell mechanics. This review aims to provide the spectrum of the most important applications of the AFM technique in medicine to date.

Measuring Cognition in Clinical Trials in Parkinson's Disease, Dementia with Lewy Bodies, and Related Disorders: Roundtable Proceedings and Roadmap for Research.

Emerging research suggests that Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share underlying pathology and may represent a single, biologically defined disease spectrum. Cognitive changes are among the most worrisome symptoms for patients with PD, and are the core feature of DLB. While the cognitive changes experienced by individuals with PD and mild cognitive impairment share some clinical characteristics with patients who have undiagnosed or prodromal DLB, these changes are distinct from other types of dementias, such as Alzheimer's disease. To spur the adaptation of existing cognition-focused measures and the development of new ones to underlie clinical trial endpoints in PD and DLB, the PD/DLB Cognition Roundtable was held on January 10 and 11, 2024, in Washington, D.C. The roundtable brought together representatives from academia and industry, as well as with representatives of regulatory agencies, community partners, patient advocates, and research funders, to build consensus and collaborate on the outcome assessment and trial design methods that will support the development of new treatments for early or mild cognitive changes in disorders on the PD/DLB spectrum. The authors of this document summarize the roundtable, discussing the state of the field for clinical trial design and cognition measures in PD and DLB, promising avenues of research, and perspectives of regulatory agencies.

Metal ions in biomedically relevant macromolecular structures.

Understanding the functions of metal ions in biological systems is crucial for many aspects of research, including deciphering their roles in diseases and potential therapeutic use. Structural information about the molecular or atomic details of these interactions, generated by methods like X-ray crystallography, cryo-electron microscopy, or nucleic magnetic resonance, frequently provides details that no other method can. As with any experimental method, they have inherent limitations that sometimes lead to an erroneous interpretation. This manuscript highlights different aspects of structural data available for metal-protein complexes. We examine the quality of modeling metal ion binding sites across different structure determination methods, where different kinds of errors stem from, and how they can impact correct interpretations and conclusions.

[Translated article] Bibliometric Study of the Advances Made in Clinical Dermatological Research in Spain from 2015 through 2021: Update of the MaIND Project and Interactive Online Map.

INTRODUCTION: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time. MATERIAL AND METHODS: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤4. RESULTS: A total of 1,674 out of the 10,199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (P<.002) and in the mean number of citation-years per article (P<.01). A total of 22 of the articles had a level of evidence >4, with a positive trend towards more articles having a higher level of evidence (P<.03). ACTAS DERMOSIFILOGRÁFICAS still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles). CONCLUSIONS: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence.

Overview on bacterial carbonic anhydrase genetic families.

Bacterial carbonic anhydrases (BCAs, EC 4.2.1.1) are indispensable enzymes in microbial physiology because they facilitate the hydration of carbon dioxide (CO2) to bicarbonate ions (HCO3-) and protons (H+), which are crucial for various metabolic processes and cellular homeostasis. Their involvement spans from metabolic pathways, such as photosynthesis, respiration, to organic compounds production, which are pivotal for bacterial growth and survival. This chapter elucidates the diversity of BCA genetic families, categorized into four distinct classes (α, ß, γ, and ι), which may reflect bacterial adaptation to environmental niches and their metabolic demands. The diversity of BCAs is essential not only for understanding their physiological roles but also for exploring their potential in biotechnology. Knowledge of their diversity enables researchers to develop innovative biocatalysts for industrial applications, including carbon capture technologies to convert CO2 emissions into valuable products. Additionally, BCAs are relevant to biomedical research and drug development because of their involvement in bacterial pathogenesis and microbial survival within the host. Understanding the diversity and function of BCAs can aid in designing targeted therapeutics that interfere with bacterial metabolism and potentially reduce the risk of infections.

Development and evaluation of a training curriculum to engage researchers on accessing and analyzing the All of Us data.

OBJECTIVE: The All of Us Evenings with Genetics (EwG) Research Program at Baylor College of Medicine (BCM), funded to engage research scholars to work with the All of Us data, developed a training curriculum for the Researcher Workbench, the platform to access and analyze All of Us data. All of Us EwG developed the curriculum so that it could teach scholars regardless of their skills and background in programming languages and cloud computing. All of Us EwG delivered this curriculum at the first annual All of Us EwG Faculty Summit in May 2022. The curriculum was evaluated both during and after the Faculty Summit so that it could be improved for future training. MATERIALS AND METHODS: Surveys were administered to assess scholars' familiarity with the programming languages and computational tools required to use the Researcher Workbench. The curriculum was developed using backward design and was informed by the survey results, a review of available resources for training users on the Researcher Workbench, and All of Us EwG members' collective experience training students. The curriculum was evaluated using feedback surveys during the Faculty Summit as well as virtual meetings and emails following the Faculty Summit. RESULTS: The evaluation results demonstrated the success of the curriculum and identified areas for improvement. DISCUSSION AND CONCLUSION: The curriculum has been adapted and improved in response to evaluations and in response to changes to the All of Us data and infrastructure to train more researchers through this program and other scholarly programs.

Provenance Information for Biomedical Data and Workflows: Scoping Review.

BACKGROUND: The record of the origin and the history of data, known as provenance, holds importance. Provenance information leads to higher interpretability of scientific results and enables reliable collaboration and data sharing. However, the lack of comprehensive evidence on provenance approaches hinders the uptake of good scientific practice in clinical research. OBJECTIVE: This scoping review aims to identify approaches and criteria for provenance tracking in the biomedical domain. We reviewed the state-of-the-art frameworks, associated artifacts, and methodologies for provenance tracking. METHODS: This scoping review followed the methodological framework developed by Arksey and O'Malley. We searched the PubMed and Web of Science databases for English-language articles published from 2006 to 2022. Title and abstract screening were carried out by 4 independent reviewers using the Rayyan screening tool. A majority vote was required for consent on the eligibility of papers based on the defined inclusion and exclusion criteria. Full-text reading and screening were performed independently by 2 reviewers, and information was extracted into a pretested template for the 5 research questions. Disagreements were resolved by a domain expert. The study protocol has previously been published. RESULTS: The search resulted in a total of 764 papers. Of 624 identified, deduplicated papers, 66 (10.6%) studies fulfilled the inclusion criteria. We identified diverse provenance-tracking approaches ranging from practical provenance processing and managing to theoretical frameworks distinguishing diverse concepts and details of data and metadata models, provenance components, and notations. A substantial majority investigated underlying requirements to varying extents and validation intensities but lacked completeness in provenance coverage. Mostly, cited requirements concerned the knowledge about data integrity and reproducibility. Moreover, these revolved around robust data quality assessments, consistent policies for sensitive data protection, improved user interfaces, and automated ontology development. We found that different stakeholder groups benefit from the availability of provenance information. Thereby, we recognized that the term provenance is subjected to an evolutionary and technical process with multifaceted meanings and roles. Challenges included organizational and technical issues linked to data annotation, provenance modeling, and performance, amplified by subsequent matters such as enhanced provenance information and quality principles. CONCLUSIONS: As data volumes grow and computing power increases, the challenge of scaling provenance systems to handle data efficiently and assist complex queries intensifies, necessitating automated and scalable solutions. With rising legal and scientific demands, there is an urgent need for greater transparency in implementing provenance systems in research projects, despite the challenges of unresolved granularity and knowledge bottlenecks. We believe that our recommendations enable quality and guide the implementation of auditable and measurable provenance approaches as well as solutions in the daily tasks of biomedical scientists. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31750.

Racial Equity, Diversity and Inclusion in Bioethics: Recommendations from the Association of Bioethics Program Directors Presidential Task Force.

Recent calls to address racism in bioethics reflect a sense of urgency to mitigate the lethal effects of a lack of action. While the field was catalyzed largely in response to pivotal events deeply rooted in racism and other structures of oppression embedded in research and health care, it has failed to center racial justice in its scholarship, pedagogy, advocacy, and practice, and neglected to integrate anti-racism as a central consideration. Academic bioethics programs play a key role in determining the field's norms and practices, including methodologies, funding priorities, and professional networks that bear on equity, inclusion, and epistemic justice. This article describes recommendations from the Racial Equity, Diversity, and Inclusion (REDI) Task Force commissioned by the Association of Bioethics Program Directors to prioritize and strengthen anti-racist practices in bioethics programmatic endeavors and to evaluate and develop specific goals to advance REDI.

What public health challenges and unmet medical needs would benefit from interdisciplinary collaboration in the EU? A survey and multi-stakeholder debate.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts' societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU's research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.