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Following recent discussions around suspended life, this paper focuses on an endeavor that sought to arrest biological material in time and space and render it available on demand. It depicts the attempt to establish a collection of cryopreserved donated cells. The study offers rare insights into how this initiative was at odds with familiar politics significant in its field, those of innovation and preparedness, and therefore was suspended itself. In identifying parallels with accounts of unsuccessful biobanks, the paper makes a case for the analytical value of considering ill-fated projects of suspension along with those that prosper and attract public attention. The case of a novel cryo-collection, in particular, demonstrates how the idea and practice of suspension only gathers political momentum when it serves other well-established rationales. As such, it prompts two important conclusions. First, the power to arrest life as it comes with cryotechnologies is much more likely to unravel in entrenched constellations than to carry transformative or disruptive potential. Second, however, the paper also exemplifies that projects of suspension are not necessarily doomed to serve hegemonic ways of governing life. It advocates for preventing such mismatches from falling into oblivion. [ABSTRACT FROM AUTHOR]

Given that lumbar disc herniation (LDH) is a prevalent spinal condition that causes significant individual suffering and societal costs, the genetic basis of LDH has received relatively little research. Our aim is to increase understanding of the genetic factors influencing LDH. We perform a genome-wide association analysis (GWAS) of LDH in the FinnGen project and in Estonian and UK biobanks, followed by a genome-wide meta-analysis to combine the results. In the meta-analysis, we identify 41 loci that have not been associated with LDH in prior studies on top of the 23 known risk loci. We detect LDH-associated loci in the vicinity of genes related to inflammation, disc-related structures, and synaptic transmission. Overall, our research contributes to a deeper understanding of the genetic factors behind LDH, potentially paving the way for the development of new therapeutics, prevention methods, and treatments for symptomatic LDH in the future. A genome-wide association study suggests 41 previously unreported loci on top of the 23 known loci that influence the disease risk for lumbar disc herniations. Many of these loci harbour genes implicated in disc structure and inflammation, as well as genes related to the nervous system and nerve function. [ABSTRACT FROM AUTHOR]

Summary: Validation of biobanks and large cancer cohorts is essential in ensuring high‐quality research results. We examined the coverage, generalisability and validity of the lymphoma collection of the Uppsala‐Umeå Comprehensive Cancer Consortium (U‐CAN) biobank in Sweden, one of the largest cancer biobanks in Europe. Up until 2022, 889 lymphoma patients in U‐CAN Uppsala had available samples, and 329 in U‐CAN Umeå. Patients diagnosed in the U‐CAN Uppsala area 2011–2021 (n = 843) were linked to the nationwide Swedish Lymphoma Register, and a subset diagnosed before 2019 (n = 727) to population‐based registers. The coverage was 39% of all lymphoma patients between 2011 and 2019 diagnosed in the U‐CAN Uppsala area, with a pandemic decline to 10% during 2020–2021. The patients included had superior overall survival (hazard ratio = 0.70 [95% confidence interval, CI: 0.60–0.82]) than all lymphoma patients in Sweden. They had better performance status, were younger (odds ratio [OR] = 0.21 [95% CI: 0.13–0.34]) and had less comorbidities (OR = 0.66 [95% CI: 0.56–0.78]). However, cause‐specific survival and stage distribution were similar. The questionnaire data captured less comorbidities compared to the national registers. Evaluations of biobanks are important, as even population‐based biobanks such as U‐CAN select younger patients with higher socioeconomical status and better performance status. However, the similar cause‐specific survival as in the registries suggests U‐CANs usefulness for prognostic biomarker studies. [ABSTRACT FROM AUTHOR]

Biobanks are becoming ubiquitous infrastructures in zoology and other non-human life sciences. They promise to store frozen research samples for the long term for future use. That use remains speculative but nevertheless needs to be anticipated. Following the establishment of a physical and digital infrastructure for frozen samples in an animal biobanking project, this article explores how the future is anticipated to remember the past, and how frozen objects are shaped accordingly. Situating the biobank between mundane freezing routines in a research lab and the 'dry' and 'wet' collections of natural history museums, I argue that frozen research objects need to be conserved in two separate ways. The unavailability of cryo-objects in cold storage forces researchers to store materials independently of metadata, while retaining a link between them that allows for their reunion after thawing. The result is a split object, leading a double life at sub-zero and room temperature, linked only through the surface of special plastic containers. Following the making of such split objects, this article offers an elaboration of Radin's 'planned hindsight' as well as a reflection on the universality and particularity of biobanks as standardized scientific memory. [ABSTRACT FROM AUTHOR]

Background/Objectives: The identification of coronary artery disease (CAD) high-risk individuals is a major clinical need for timely diagnosis and intervention. Many different polygenic scores (PGSs) for CAD risk are available today to estimate the genetic risk. It is necessary to carefully choose the score to use, in particular for studies on populations, which are not adequately represented in the large datasets of European biobanks, such as the Italian one. This work aimed to analyze which PGS had the best performance within the Italian population. Methods: We used two Italian independent cohorts: the EPICOR case–control study (576 individuals) and the Atherosclerosis, Thrombosis, and Vascular Biology (ATVB) Italian study (3359 individuals). We evaluated 266 PGS for cardiovascular disease risk from the PGS Catalog, selecting 51 for CAD. Results: Distributions between patients and controls were significantly different for 49 scores (p-value < 0.01). Only five PGS have been trained and tested for the European population specifically. PGS003727 demonstrated to be the most accurate when evaluated independently (EPICOR AUC = 0.68; ATVB AUC = 0.80). Taking into account the conventional CAD risk factors further enhanced the performance of the model, particularly in the ATVB study (p-value = 0.0003). Conclusions: European CAD PGS could have different risk estimates in peculiar populations, such as the Italian one, as well as in various geographical macro areas. Therefore, further evaluation is recommended for clinical applicability. [ABSTRACT FROM AUTHOR]

Background and Objectives: Data provided from blood donors have contributed to the understanding of public health epidemiology and policy decisions. A recent example was during the severe acute respiratory syndrome‐related coronavirus (SARS‐CoV‐2) pandemic when blood services monitored the seroprevalence in blood donors. Based on this experience, blood services have the opportunity to expand their role and participate in public health surveillance and research. The aim of this report is to share available resources to assist blood services in this area. Materials and Methods: The Surveillance, Risk Assessment and Policy (SRAP) Sub‐group of the International Society of Blood Transfusion (ISBT) Transfusion Transmitted Infectious Diseases (TTID) Working Party developed a Public Health Research Toolkit to assist blood services and researchers interested in expanding their role in public health research. Results: The ISBT Public Health Research Toolkit provides resources for what blood services can offer to public health, examples of donor research studies, the utility of donor data and website links to public health agencies. The toolkit includes a customizable template for those interested in establishing and managing a biobank. Conclusion: The ISBT Public Health Research Toolkit includes resources to increase the recognition of the role blood donors can play in public health and to help blood services gain commitment and funding from various agencies for new research and surveillance. [ABSTRACT FROM AUTHOR]

Abstract Biobanks are valuable service units that ensure the usage of high-quality biological samples. They contribute to translational research, and their support may improve future therapeutic approaches. They store biological samples that can be used to examine circulation biomarkers, immune cells, and immunohistochemistry aspects of illnesses and further in-depth examinations using NGS techniques. The IRCCS Synlab SDN Biobank has about 70,000 well-preserved cryopreserved human samples from various diseases, primarily oncological but also neurological and cardiovascular. These biospecimens were taken from 25,000 participants underwent imaging with a contrast agent. The goal is to propose quality control assays that meet the requirements of the international standard ISO 9001:2015 and ISO 20387:2020 accreditation. PBMCs viability was determined, and immune subset cells were analyzed by flow cytometry. Furthermore, the expression of ubiquitous miRNAs was used to assess plasma sample integrity. The quality controls demonstrated that the biological samples were correctly cryopreserved; the preservation of human biological samples did not affect the quality of the biological samples tested. Indeed, the cryopreserved PBMCs had a vitality of more than 80%, and the lymphocyte subsets could be selected for future immune cell investigations. Furthermore, miRNA expression was highest in thawed plasma samples compared to the positive and negative controls. We evaluated the quality of our randomly selected biobank-thawed human samples. Both PBMCs and plasma samples fulfill the high-quality standards needed for biomedical research, assuring their long-term preservation. However, further research is needed in the biobanking field to establish globally accepted procedures to confirm the quality of biological samples.

The alarming pace of species extinction severely threatens terrestrial and aquatic ecosystems, undermining the crucial ecological services vital for environmental sustainability and human well-being. Anthropogenic activities, such as urbanization, agriculture, industrialization, and those inducing climate change, intensify these risks, further imperiling biodiversity. Of particular importance are aquatic organisms, pivotal in biodiscovery and biotechnology. They contribute significantly to natural product chemistry, drug development, and various biotechnological applications. To safeguard these invaluable resources, establishing and maintaining aquatic biomaterial repositories (ABRs) is imperative. This review explores the complex landscape of ABRs, emphasizing the need for standardized procedures from collection to distribution. It identifies key legislative and regulatory frameworks, such as the Nagoya Protocol and EU directives, essential for ensuring responsible and equitable biorepository operations. Drawing on extensive literature and database searches, this study compiles existing recommendations and practices into a cohesive framework with which to guide the establishment and sustainable management of ABRs. Through collaborative efforts and adherence to best practices, ABRs can play a transformative role in the future of marine biotechnology and environmental conservation. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis is a prevalent musculoskeletal condition, but the role of specific serum biomarkers, such as calcium, vitamin D, and C-reactive protein (CRP), in predicting mortality among individuals with osteoarthritis remains unclear. Methods: This observational study analyzed longitudinal data from over 500,000 participants in the UK Biobank, identifying those with osteoarthritis using ICD-9/10 codes or self-reported history. We performed multivariable cox-regression and flexible parametric survival model (FPSM) for survival analysis, with adjustments made through the inverse probability of treatment weight (IPTW) for baseline covariates identified by directed acyclic graphs (DAGs). Results: Of the 49,082 osteoarthritis population, the average age was 60.69 years, with 58.7% being female. During the follow-up period exceeding 15 years, a total of 5,522 people with osteoarthritis died. High serum calcium levels, compared to normal serum calcium levels, were significantly associated with all-cause mortality (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11, 1.59), cardiovascular diseases (CVD)-related deaths (HR 1.55, 95% CI 1.05, 2.29), and other deaths (HR 1.59, 95% CI 1.20, 2.11). Low serum calcium levels, compared to normal serum calcium levels, was linked with CVD-related deaths (HR 2.06, 95% CI 1.02, 4.14). Vitamin D insufficiency, compared to sufficient vitamin D levels, was correlated with all-cause mortality (HR 1.22, 95% CI 1.13, 1.33), CVD-related deaths (HR 1.43, 95% CI 1.20, 1.72), and other deaths (HR 1.26, 95% CI 1.09, 1.45) but not with cancer-related deaths. High serum CRP levels, compared to normal CRP levels, were associated with all outcomes (all-cause mortality: HR 1.22, 95% CI 1.12, 1.33; CVD-related death: HR 1.24, 95%CI 1.03, 1.49; cancer-related death: HR 1.23, 95% CI 1.09, 1.40; other deaths: HR 1.19, 95%CI 1.03, 1.38). Conclusions: Both high and low serum calcium levels, elevated CRP, and vitamin D insufficiency are potential predictors of increased mortality risk in the osteoarthritis population. These findings emphasize the importance of monitoring and possibly addressing these serum biomarkers in osteoarthritis populations to improve long-term outcomes. Further studies are needed to understand the underlying mechanisms and to propose therapeutic interventions. [ABSTRACT FROM AUTHOR]

Arterial stiffening and changes in brain structure both occur with normal aging and can be exacerbated via acquired health conditions. While cross-sectional associations exist, the longitudinal relationship between arterial stiffness and brain structure remains unclear. In this study, we investigated 1) associations between baseline arterial stiffness index (ASI) and brain structure (global and regional grey matter volumes (GMV), white matter hyperintensities (WMH)) 10-years post-baseline (10.4±0.8 years) and 2) associations between the 10-year change in ASI from baseline and brain structure 10-years post-baseline in 650 healthy middle- to older-aged adults (53.4±7.5 years) from the UK Biobank. We observed significant associations between baseline ASI and GMV (p<0.001) and WMH (p=0.0036) 10-years post-baseline. No significant associations between 10-year change in ASI and brain structure (global GMV p=0.24; WMH volume p=0.87) were observed. There were significant associations of baseline ASI in 2 of 60 regional brain volumes analyzed (right posterior superior temporal gyrus p=0.001; left superior lateral occipital cortex p<0.001). Strong associations with baseline ASI, but not changes in ASI over 10-years, suggest arterial stiffness at the entry point of older adulthood is more impactful on brain structure 10-years later compared to age-related stiffening. Based on these associations, we suggest clinical monitoring and potential intervention for reducing arterial stiffness should occur in midlife to reduce vascular contributions to structural changes in the brain, supporting a healthy trajectory of brain aging. Our findings also support use of ASI as a surrogate for gold standard measures in showing overall relationships between arterial stiffness and brain structure. [ABSTRACT FROM AUTHOR]

Biobanks of human biosamples and cell lines are indispensable for biomedical research on human health and disease and for drug development projects. Many human cell line biobanks worldwide hold collections of lymphoblastoid cell lines (LCLs), representing thousands of affected and control donors from diverse ethnic/ancestry groups. In recent years, induced human pluripotent stem cells (iPSCs) and differentiated human cells derived from these iPSCs have become indispensable for applied biomedical research. Establishing iPSCs remains a laborious and costly step towards generating differentiated human cells. To address this research need, several non‐profit and commercial biobanks have established iPSC collections for distribution to researchers, thereby serving as a resource for generating differentiated human cells. The most common starting materials for generation of iPSCs are a skin biopsy for harvesting fibroblasts, or a blood sample for collection of peripheral blood mononuclear cells. However untapped resources include the large established collections of biobanked human LCLs which can be reprogrammed to iPSCs using a variety of published protocols including the use of non‐integrating episomal vectors. Many biobanks curate LCLs from diverse ethnic/ancestry populations, an aspect largely absent in most established iPSC biobanks which tend to primarily reflect populations from developed countries. Here, we call upon researchers across the breadth of iPSC research to tap the unique resource of existing and diverse human LCL collections for establishing biobanked iPSC panels that better represent the varied human ethnic (and hence genomic) diversity, thereby benefiting precision medicine and drug development research on a global scale. [ABSTRACT FROM AUTHOR]

Methods of estimating polygenic scores (PGSs) from genome-wide association studies are increasingly utilized. However, independent method evaluation is lacking, and method comparisons are often limited. Here, we evaluate polygenic scores derived via seven methods in five biobank studies (totaling about 1.2 million participants) across 16 diseases and quantitative traits, building on a reference-standardized framework. We conducted meta-analyses to quantify the effects of method choice, hyperparameter tuning, method ensembling, and the target biobank on PGS performance. We found that no single method consistently outperformed all others. PGS effect sizes were more variable between biobanks than between methods within biobanks when methods were well tuned. Differences between methods were largest for the two investigated autoimmune diseases, seropositive rheumatoid arthritis and type 1 diabetes. For most methods, cross-validation was more reliable for tuning hyperparameters than automatic tuning (without the use of target data). For a given target phenotype, elastic net models combining PGS across methods (ensemble PGS) tuned in the UK Biobank provided consistent, high, and cross-biobank transferable performance, increasing PGS effect sizes (β coefficients) by a median of 5.0% relative to LDpred2 and MegaPRS (the two best-performing single methods when tuned with cross-validation). Our interactively browsable online-results and open-source workflow prspipe provide a rich resource and reference for the analysis of polygenic scoring methods across biobanks. [Display omitted] Systematic evaluation of polygenic scoring methods in 1.2 million individuals across five biobanks finds that no single method performs best. Performance varied more between biobanks than between methods, suggesting that future research should address between-biobank variability. Ensembles provided high, robust, and transferable performance. Workflow and results browser are open source. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) are amongst the most promising candidates for developing blood-based biomarkers. However, patient sample availability is a key barrier to translational research whilst most biobanks store samples of 1.5mL volume or less. To date, there is no consensus on the most suitable method of EV separation and current techniques frequently require large volumes of biofluids, complicated technology, technical expertise, or significant operating costs, which prevents their widespread adoption by less EV-focussed laboratories. Therefore, there is a need for an easy and reproducible method that separates representative EVs from clinically relevant 1mL volumes of plasma prior to subsequent biomarker identification. Methods: In this study, EVs were separated from a clinically relevant 1mL volume of human plasma using four different separation techniques: size exclusion chromatography (SEC), differential ultracentrifugation, precipitation, and immunoaffinity magnetic bead capture. The EVs were characterised using several orthogonal techniques (protein quantification, nanoparticle tracking analysis, transmission electron microscopy, Western blot, single particle interferometric reflectance imaging sensing, and mass spectrometry-based proteomics) to comprehensively compare the separated samples. Results: We provide examples of anticipated results highlighting that SEC-processed samples have greater protein quantification yield, greater particle yield of the expected size for EVs, and sufficient EV purity, which facilitates effective EV cargo assessment by proteomics. Moreover, we confirm significant overlap with known EV-related proteins within the Vesiclepedia database. Additionally, using single particle interferometric reflectance imaging sensing (Leprechaun®), we identify that SEC has the most representative surface tetraspanin distribution of the separated EV population compared to unprocessed plasma. Discussion: Given that SEC requires minimal expertise, no complicated technology and can separate EVs within 90 min, this comparison reinforces SEC as a clinically relevant EV separation method from 1mL of plasma making it suitable for widespread implementation. [ABSTRACT FROM AUTHOR]

There has been intense debate within the autistic and autism communities about the use of autism biobanks – repositories containing biological and phenotypic materials – and of genomic autism research more broadly. Here, we sought to understand the views and experiences of those contributing to one specific biobank, the Australian Autism Biobank. We adopted a multi-informant approach, conducting semi-structured interviews with 77 people, including 18 autistic probands, 46 parents and seven siblings, all of whom donated material to the Biobank, as well as six researchers employed on the project. Specifically, we asked: what motivated participants and researchers to contribute to the Australian Autism Biobank? And how did they feel about their involvement in that process? We analysed the data using reflexive thematic analysis, adopting an inductive approach within an essentialist framework. We identified three themes, which revealed a wide diversity of viewpoints, including positive conceptualisations of autism linked to neurodiversity and more negative conceptualisations linked to hopes for the development of genetic screening and reproductive choice. These findings have implications for the meaning, value and future directions of autism science. This research has been conducted using the Australian Autism Biobank resource. A lot of autism research has focused on finding genes that might cause autism. To conduct these genetic studies, researchers have created 'biobanks' – collections of biological samples (such as blood, saliva, urine, stool and hair) and other health information (such as cognitive assessments and medical histories). Our study focused on the Australian Autism Biobank, which collected biological and health information from almost 1000 Australian autistic children and their families. We wanted to know what people thought about giving their information to the Biobank and why they chose to do so. We spoke to 71 people who gave to the Biobank, including 18 autistic adolescents and young adults, 46 of their parents and seven of their siblings. We also spoke to six researchers who worked on the Biobank project. We found that people were interested in giving their information to the Biobank so they could understand why some people were autistic. Some people felt knowing why could help them make choices about having children in the future. People also wanted to be involved in the Biobank because they believed it could be a resource that could help others in the future. They also trusted that scientists would keep their information safe and were keen to know how that information might be used in the future. Our findings show that people have lots of different views about autism biobanks. We suggest researchers should listen to these different views as they develop their work. [ABSTRACT FROM AUTHOR]

In recent years, medicine has undergone profound changes, strongly entering a new phase defined as the "era of precision medicine". In this context, patient clinical management involves various scientific approaches that allow for a comprehensive pathology evaluation: from preventive processes (where applicable) to genetic and diagnostic studies. In this scenario, biobanks play an important role and, over the years, have gained increasing prestige, moving from small deposits to large collections of samples of various natures. Disease-oriented biobanks are rapidly developing as they provide useful information for the management of complex diseases, such as melanoma. Indeed, melanoma, given its highly heterogeneous characteristics, is one of the oncologic diseases with the greatest clinical and therapeutic management complexity. So, the possibility of extrapolating tissue, genetic and imaging data from dedicated biobanks could result in more selective study approaches. In this review, we specifically analyze the several biobank types to evaluate their role in technology development, patient monitoring and research of new biomarkers, especially in the melanoma context. [ABSTRACT FROM AUTHOR]

The biobanks from dermal biopsies represent an interesting strategy for biodiversity conservation. Nevertheless, the morphological and cellular patterns of the dermis can be influenced by the age and sex of the individual. Therefore, evaluating these factors is interesting for forming biobanks of Antillean manatees. These animals, representatives of marine fauna, have had their population reduced, and biobanks are essential for their conservation. Then, we evaluated the effects of age (3.5 years vs. 3.6–16 years vs. 23.6 years) and sex (males vs. females) on morphological and cellular parameters using histological and in vitro culture techniques. Regardless of age, no differences were observed for dermal thickness, collagen fibres, tissue proliferative activity and viable cell recovery. Nonetheless, fibroblast reduction was observed in groups aged 23.6 years compared to other animals (p < 0.05). Additionally, cells from animals aged 3.6–16 years showed more significant mitochondrial damage than the other groups (p < 0.05). Regardless of sex, no differences were observed for dermal thickness, collagen fibres, tissue proliferative activity and viable cell recovery; however, females had fewer fibroblasts than males (p < 0.05). Cells from females showed lower mitochondrial damage when compared to cells from males. In summary, although age and sex do not influence dermal thickness and cell recovery, variations in the number of fibroblasts and mitochondrial characteristics were observed among the groups. These differences may be significant for understanding the dermis aspects to be correlated to biobank systems. [ABSTRACT FROM AUTHOR]

Population biobanks are an increasingly important infrastructure to support research and will be a much-needed resource in the delivery of personalised medicine. Artificial intelligence (AI) systems can process and cross-link very large amounts of data quickly and be used not only for improving research power but also for helping with complex diagnosis and prediction of diseases based on health profiles. AI, therefore, potentially has a critical role to play in personalised medicine, and biobanks can provide a lot of the necessary baseline data related to healthy populations that will enable the development of AI tools. To develop these tools, access to personal data, and in particular, sensitive data, is required. Such data could be accessed from biobanks. Biobanks are a valuable resource for research but accessing and using the data contained within such biobanks raise a host of legal, ethical, and social issues (ELSI). This includes the appropriate consent to manage the collection, storage, use, and sharing of samples and data, and appropriate governance models that provide oversight of secondary use of samples and data. Biobanks have developed new consent models and governance tools to enable access that address some of these ELSI-related issues. In this paper, we consider whether such governance frameworks can enable access to biobank data to develop AI. As Italy has one of the most restrictive regulatory frameworks on the use of genetic data in Europe, we examine the regulatory framework in Italy. We also look at the proposed changes under the European Health Data Space (EHDS). We conclude by arguing that currently, regulatory frameworks are misaligned and unless addressed, accessing data within Italian biobanks to train AI will be severely limited. [ABSTRACT FROM AUTHOR]

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The UCLA ATLAS Community Health Initiative (ATLAS) has an initial target to recruit 150,000 participants from across the UCLA Health system with the goal of creating a genomic database to accelerate precision medicine efforts in California. This initiative includes a biobank embedded within the UCLA Health system that comprises de-identified genomic data linked to electronic health records (EHRs). The first freeze of data from September 2020 contains 27,987 genotyped samples imputed to 7.9 million SNPs across the genome and is linked with de-identified versions of the EHRs from UCLA Health. Here, we describe a centralized repository of the genotype data and provide tools and pipelines to perform genome- and phenome-wide association studies across a wide range of EHR-derived phenotypes and genetic ancestry groups. We demonstrate the utility of this resource through the analysis of 7 well-studied traits and recapitulate many previous genetic and phenotypic associations.

The HUNT Biobank in Norway holds biological samples from 110,000 participants in the HUNT Study. The biobank contains a variety of samples, including blood, DNA, urine, and fecal samples, which are available for research purposes. The biobank has a unique identification number for each participant, allowing for linkage to local and national registries. The data and samples from the biobank are accessible to national and international research groups. The HUNT Study is a valuable resource for epidemiological studies, disease risk prediction, and clinical translation. The biobank collects and stores various types of samples, which are processed and stored at specific temperatures. The biobank uses a Laboratory Information Management System to manage and track the samples. The storage facilities include liquid nitrogen freezers, chest freezers, and automatic storage systems. The biobank also conducts DNA and RNA extractions, quality assurance, and biomarker analyses. The data and samples from the HUNT Biobank are accessible to researchers with approval from the Regional Committee for Medical and Health Ethics. [Extracted from the article]

While model organisms have had many historians, this article places studies of humans, and particularly our development, in the politics of species choice. Human embryos, investigated directly rather than via animal surrogates, have gone through cycles of attention and neglect. In the past 60 years they moved from the sidelines to center stage. Research was resuscitated in anatomy, launched in reproductive biomedicine, molecular genetics, and stem-cell science, and made attractive in developmental biology. I explain this surge of interest in terms of rivalry with models and reliance on them. The greater involvement of medicine in human reproduction, especially through in vitro fertilization, gave access to fresh sources of material that fed critiques of extrapolation from mice and met demands for clinical relevance or "translation." Yet much of the revival depended on models. Supply infrastructures and digital standards, including biobanks and virtual atlases, emulated community resources for model organisms. Novel culture, imaging, molecular, and postgenomic methods were perfected on less precious samples. Toing and froing from the mouse affirmed the necessity of the exemplary mammal and its insufficiency justified inquiries into humans. Another kind of model—organoids and embryo-like structures derived from stem cells—enabled experiments that encouraged the organization of a new field, human developmental biology. Research on humans has competed with and counted on models. [ABSTRACT FROM AUTHOR]

In this essay, I use two literary works from two distinct genres and with two very different narratives - a satirical techno-thriller and a historical non-fiction piece - to show how they can both convey the same bioethical message - donation of human body parts - to their audience. The two books I examine and contrast here are Rebecca Skloot's The Immortal Life of Henrietta Lacks (2010) and Michael Crichton's satirical techno-thriller Next (2006). The main question this article will try to answer is obviously not why The Immortal Life of Henrietta Lacks, a carefully researched nonfiction book, belongs on the list of essential works on bioethics, but rather why Next, a satirical techno-thriller that continuously blurs the boundaries between fact and fiction, belongs on the list as well. [ABSTRACT FROM AUTHOR]

Introduction: The development of the scientific potential linked with biobanking and research on human biological material is highly dependent on the willingness of potential donors to cooperate with entities that collect the material. For this reason, it is crucial to identify the circumstances and factors that may encourage potential participants to donate their biological material. In particular, knowledge of the motivational factors that can be modified by the persons managing a biobank may prove notably important for shaping the organizational and communication policy of the biobank and other scientific institutions. Material and methods: The research was carried out on a group of 1,100 people over 18 years of age representing the adult population of Poland in 2021. Results: More than half of the respondents declared their willingness to donate a blood sample for research purposes to a biobank (57.8%). The most often indicated incentives among the factors supporting the donation of biological material were offers of: obtaining the results of genetic tests predicting the risk of diseases (77.1%), blood tests (71.3%), the possibility of obtaining a small remuneration (64.6%) and the carrying out of genetic ancestry tests (60.4%). Conclusion: Offering the possibility of performing additional diagnostic tests, especially genetic tests, may significantly increase the willingness of potential donors to cooperate with biobanks and other entities collecting human biological material for the purpose of scientific research. However, attention should also be paid to the challenges and risks linked with respecting the privacy and autonomy of research participants. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the biobank awareness among Polish pharmacy students and how it affects their support for biobank research. Methods: A survey among 366 pharmacy students enrolled at two Polish medical universities: the Poznań University of Medical Sciences and Medical University of Lublin was conducted. Results: Although most pharmacy students felt positivity about biobanking and expressed the willingness to donate their biospecimens for biomedical research, their awareness on research biobanks was low. Their willingness to participate was driven by the desire to benefit society, help advance science and develop new therapies. While students supported donation for most types of research, biobanks run by medical universities were the highest trusted research institutions. The primary factors associated with student's willingness to participate were religiosity and place of study. Notably, nonreligious students and those studying in Poznan exhibited more favourable attitudes toward donating for research and expressed greater support for the establishment of research biobanks in Poland. Conclusion: Since biobank awareness among future pharmacists is inadequate incorporating biobank competency domains into education and training of pharmacists is required. [ABSTRACT FROM AUTHOR]

Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse 'use conditions'. We report a core lexicon of terms that are atomic, non-directional 'concepts of use', called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use. [ABSTRACT FROM AUTHOR]

While biobanking is expanding globally, the empirical evidence concerning the impact of religion on future healthcare professionals' awareness and willingness to donate biospecimens for biobank research is lacking. To understand how medical students' religious beliefs can fuel their questions regarding how biospecimens would be stored, cared for, and used, we conducted a survey among 1500 medical students at Poznań University of Medical Sciences. Our findings suggest that, while both religious and nonreligious students supported the idea of biobanking of human biological material and were willing to donate for research purposes, nonreligious students felt more positive toward biobanking, supported the idea of establishing biobanks in Poland more often, and were more eager to donate most types of tissues and to participate in biobank research. Religious beliefs were also associated with medical students' perception of benefits and risks resulting from biobanking, perceived trust toward various biobank institutions, and preferred type of consent. [ABSTRACT FROM AUTHOR]

The availability of biomaterials is a key component of health research and the development of new health-technologies (including, diagnostics, medicines, and vaccines). People are often encouraged by biobanks to donate samples altruistically to such biobanks. While empirical evidence suggests many donors are motivated by the desire to contribute towards developing new health-technologies for society. However, a tension can arise as health-technologies whose development is contributed to by donors' biomaterials will often be protected by intellectual property rights (IPRs), including patents. Patents give rightsholders control over how patented technologies are used and can be used in a way that impedes public access to technologies developed. Yet, there are no binding European legal obligations mandating disclosure to donors of how IPRs can operate over downstream health-technologies and how they could impact access to health-technologies developed, nor are there legally binding obligations to ensure public accessibility of technologies developed. Focusing on the bioethical implications posed, this article argues that the current situation can impact donors' autonomy and dignity interests. A more holistic approach is needed for biobank donation, which embeds a consideration of donors' expectations/interests from the point of donation through to how such samples are used and how health-technologies developed are accessed. We put forward avenues that seek to address such issues. [ABSTRACT FROM AUTHOR]

Background Models with polygenic risk scores and clinical factors to predict risk of different cancers have been developed, but these models have been limited by the polygenic risk score–derivation methods and the incomplete selection of clinical variables. Methods We used UK Biobank to train the best polygenic risk scores for 8 cancers (bladder, breast, colorectal, kidney, lung, ovarian, pancreatic, and prostate cancers) and select relevant clinical variables from 733 baseline traits through extreme gradient boosting (XGBoost). Combining polygenic risk scores and clinical variables, we developed Cox proportional hazards models for risk prediction in these cancers. Results Our models achieved high prediction accuracy for 8 cancers, with areas under the curve ranging from 0.618 (95% confidence interval = 0.581 to 0.655) for ovarian cancer to 0.831 (95% confidence interval = 0.817 to 0.845) for lung cancer. Additionally, our models could identify individuals at a high risk for developing cancer. For example, the risk of breast cancer for individuals in the top 5% score quantile was nearly 13 times greater than for individuals in the lowest 10%. Furthermore, we observed a higher proportion of individuals with high polygenic risk scores in the early-onset group but a higher proportion of individuals at high clinical risk in the late-onset group. Conclusion Our models demonstrated the potential to predict cancer risk and identify high-risk individuals with great generalizability to different cancers. Our findings suggested that the polygenic risk score model is more predictive for the cancer risk of early-onset patients than for late-onset patients, while the clinical risk model is more predictive for late-onset patients. Meanwhile, combining polygenic risk scores and clinical risk factors has overall better predictive performance than using polygenic risk scores or clinical risk factors alone. [ABSTRACT FROM AUTHOR]

Multi-parametric magnetic resonance imaging (mpMRI) has emerged as an important tool for identifying clinically significant prostate cancer. We examined if the addition of a 400-variant multi-ancestry polygenic risk score (PRS) to mpMRI has the potential to improve identification. Based on data from 24 617 men from the Mass General Brigham Biobank, we identified 1243 men who underwent mpMRI. Men in the top PRS quartile were more likely to have clinically significant prostate cancer (47.1% vs 28.6% in the bottom PRS quartile, adjusted relative proportion 1.72 [95% CI = 1.35 to 2.19]). Both among men with a positive and a negative mpMRI, men in the top PRS quartile had the highest frequency of clinically significant cancer. In a constructed scenario for selecting men to undergo biopsy, use of the PRS lowered the frequency of missed clinically significant cancers from 9.1% to 5.9%. Our study provides initial support for using the PRS to improve identification of potentially lethal prostate cancer. [ABSTRACT FROM AUTHOR]

The increasing aging of the human population is currently and for the coming decades a major public health issue in many countries, requiring the implementation of global public health policies promoting healthy and successful aging. Individuals are not equal in the face of aging and some can present exceptional healthspan and/or lifespan, which are notably influenced by both genetic and environmental factors. Research and studies on human aging, healthy aging and longevity should rely in particular on cohorts of long-lived individuals, also including biological samples allowing studies on the biology of aging and longevity. In this manuscript, we provide for the first time a complete description of the CEPH (Centre d'Etude du Polymophisme Humain) Aging cohort, an exceptional cohort recruited during the 90s to 2000s, including more than 1700 French long-lived individuals (≥ 90 years old) born between 1875 and 1916 as well as for some of them their siblings and offspring. Among the participants, 1265 were centenarians, including 255 semi-supercentenarians ([105–110] years old) and 25 supercentenarians (≥ 110 years old). The available anthropometric, epidemiologic and clinical data for the cohort participants are described and especially the collection of blood-derived biological samples associated with the cohort which includes DNA, cryopreserved cells and cell lines, plasma, and serum. This biological collection from the first cohort of centenarians in the world is an inestimable resource for ongoing and future molecular, cellular, and functional studies aimed at deciphering the mechanisms of human (successful) aging and longevity. [ABSTRACT FROM AUTHOR]

The ear tissue of vulnerable felines, such as the puma, holds potential biological material for creating biobanks. However, skin composition can differ significantly between individuals of the of the same species and even between sexes, based on different environments. Therefore, identifying morphological similarities across these populations is crucial for developing accurate protocols. This study aimed to characterize and evaluate the structure and composition of ear skin in both a male and a female puma using histological techniques. Histomorphometric analysis revealed a total thickness of 304.65 µm and 238.95 µm for the male and the female, respectively. The epidermis was notably thinner in the female compared to the male. Specifically, the thickness of the basal, spinous, and corneum layers in the female was 2.62 µm, 10.07 µm, and 3.15 µm, respectively, compared to 3.49 µm, 13.94 µm, and 3.66 µm in the male, respectively. Melanocytes, keratinocytes, and fibroblasts totaled 26, 24, and 50 cells in the male and 21, 25, and 54 cells in the female. Moreover, chondrocytes (male: n=33 and female: n=41) and perichondrium (male=13.99 µm and female=9.05 µm) were observed in the cartilage. These results demonstrate the histomorphometric differences and similarities between a male and a female puma, consistent with observation in other felines. This information is relevant for a targeted approach for establishing biobanks for this species.

Since the biobanks’ inception in 1980, millions of human biological samples have been stored worldwide for medical research or treatment purposes. Today the secondary use of biobanks plays an increasingly important role in research projects because it allows large-scale research starting from professional collections of biospecimens and related clinical data. It would be limiting, in the “-omics” era, to not consider the enormous potential value to law enforcement of these biospecimens, where the availability of high-performance techniques makes it possible to obtain a large amount of data, even within a single session. Therefore, the quality of the sample, in addition to the associated clinical information, becomes of crucial importance to derive scientifically valid information, including for forensic research purposes. Proposing the introduction of the concept of “solidarity”, traditionally applied only to medical and research biobanks, led to public commitment to forensic medicine. Granting the forensic researcher this possibility certainly raises some questions regarding regulatory and ethical aspects of consent, privacy, confidentiality, transparency, and participant/donor trust. Since the debate has not stopped since the origin of biobanks, this review aims to explore the state of the art relating to the use of human biological material in medical biobanks for biomedical and forensic research.

Introduction: Veterinary biobanks store samples for future use and distribute samples to academic researchers and industry entities; however, informed consent provided by owners for pets contributing to biobanks can be complicated by limited understanding of goals, purpose, and logistics of biobanking. Methods: This survey-based study aimed to gather feedback from pet owners on how they viewed allowing their pet to contribute to a veterinary biobank, with the goal of identifying opportunities to improve education, awareness of veterinary biobanking initiatives, and the consent processes. An electronic survey was distributed to a listserv of 2,119 pet owners and responses were received from 118 respondents (5.6%). Results: Most respondents (67%) were not familiar with the concept of veterinary biobanking prior to having responded to the survey. Most (89%) were willing to allow their healthy pet to contribute samples to a veterinary biobanking program. Ninety-five percent would allow their sick pet to contribute. Most were neutral about financial incentives as a motivator to participate, although 40% indicated that if their pet's condition resulted in a decision to humanely euthanize, they would be more likely to contribute to the biobank if the veterinary biobanking program covered the cost of euthanasia. Common concerns included security/ confidentiality (36%), that results would not be shared with them (33%) or that samples would be used for other purposes beyond those advertised (22%). Discussion: These results suggest veterinary biobanking initiatives are well received by owners and most are willing to allow their pets to participate. Respondent concerns represent opportunities for veterinary biobanks to improve messaging and dissemination of results from work they support. [ABSTRACT FROM AUTHOR]

Since the biobanks' inception in 1980, millions of human biological samples have been stored worldwide for medical research or treatment purposes. Today the secondary use of biobanks plays an increasingly important role in research projects because it allows large-scale research starting from professional collections of biospecimens and related clinical data. It would be limiting, in the "-omics" era, to not consider the enormous potential value to law enforcement of these biospecimens, where the availability of high-performance techniques makes it possible to obtain a large amount of data, even within a single session. Therefore, the quality of the sample, in addition to the associated clinical information, becomes of crucial importance to derive scientifically valid information, including for forensic research purposes. Proposing the introduction of the concept of "solidarity", traditionally applied only to medical and research biobanks, led to public commitment to forensic medicine. Granting the forensic researcher this possibility certainly raises some questions regarding regulatory and ethical aspects of consent, privacy, confidentiality, transparency, and participant/donor trust. Since the debate has not stopped since the origin of biobanks, this review aims to explore the state of the art relating to the use of human biological material in medical biobanks for biomedical and forensic research. [ABSTRACT FROM AUTHOR]

Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine. [ABSTRACT FROM AUTHOR]

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5 -based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies. [ABSTRACT FROM AUTHOR]

The Taihu Biobank of Tumour Biomarkers (TBTB) study is a large-scale research project conducted in Wuxi, China, with the aim of understanding the prevalence, incidence, and mortality rates of cancer in middle-aged and elderly urban populations. The study recruited over 500,000 participants aged 45 and older and collected baseline data through physical examinations, serum tumor biomarkers, and questionnaire surveys. The study has identified thousands of new cancer cases and encourages collaborations with researchers worldwide. The study provides valuable data on demographic and health-related variables, laboratory test results, and the most commonly diagnosed cancers. However, there are limitations to the study, such as the lack of information on early life exposures and limited data on lifestyle factors. Researchers interested in the study are welcome to collaborate. [Extracted from the article]

A recent study published in BMC Global & Public Health examined the relationship between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines and the risk of lifestyle-related cancers. The study, conducted using the UK Biobank cohort, found that higher adherence to the guidelines was associated with a lower risk of cancer, including breast, colorectal, and gallbladder cancers. The findings highlight the potential of lifestyle changes in cancer prevention and provide valuable insights for public health policies and cancer prevention strategies. The study also emphasizes the importance of ongoing research to understand the molecular mechanisms underlying these guidelines and develop personalized cancer prevention strategies. [Extracted from the article]

Objectives: Osteoporosis, a prevalent skeletal disorder characterized by reduced bone strength, is closely linked to the IGF system, crucial for skeletal metabolism. However, the precise nature of this relationship remains elusive. In this study, we employed Mendelian randomization (MR) to unravel the associations between genetically predicted serum IGF system member levels and osteoporosis. Methods: A two-sample MR approach was employed to investigate these causal associations based on two individual datasets. Predictions of 14 serum levels of IGF system members were made using 11,036,163 relevant Single Nucleotide Polymorphisms (SNPs) within a cohort of 4,301 individuals of European descent. Genetic association estimates for osteoporosis were derived from two publicly available GWAS consortia: the Finnish consortium from the FinnGen biobank, comprising 212,778 individuals of Finnish descent (3,203 cases and 209,575 controls), and the UK consortium from the UK Biobank, including 337,159 individuals of European descent (5,266 cases and 331,893 controls). Results: According to the UK dataset, IGF-1 levels were associated with a reduced risk of osteoporosis, as indicated by the weighted median method (Odds Ratio [OR] = 0.998, 95% CI = 0.997-1.000, P = 0.032). Additionally, higher levels of IGFBP-3 were linked to a decreased risk of osteoporosis using the Inverse-Variance Weighted (IVW) method (OR = 0.999, 95% CI = 0.998-1.000, P = 0.019), and CTGF levels exhibited a negative association with osteoporosis, as determined by the weighted median method (OR = 0.998, 95% CI = 0.996-0.999, P = 0.004). In the FinnGen dataset, IGF-1 and IGFBP-3 were not identified to be associated with osteoporosis. While, IGF-LR1 levels displayed a negative association with osteoporosis, according to the MR-Egger method (OR = 0.886, 95% CI = 0.795-0.987, P = 0.036), while CYR61 was linked to an increased risk of osteoporosis based on both the weighted median and IVW methods (OR = 1.154, 95% CI = 1.009-1.319, P = 0.037, and OR = 1.115, 95% CI = 1.022-1.215, P = 0.014, respectively). Conclusion: This study provides compelling evidence that certain IGF family members play a role in the pathogenesis of osteoporosis between different datasets, indicating population specific causal effects between IGF family and osteoporosis. Although the results from both datasets demonstrated that IGF family involved in the pathogenesis of osteoporosis, but the responding key molecules might be various among different population. Subsequent research is warranted to evaluate the potential of these biomarkers as targets for osteoporosis prevention and treatment in specific population. [ABSTRACT FROM AUTHOR]

This study aims to know the attitude and perceptions of biobanks among the general public and their willingness to donate bio specimens from a hospital in India. Biobanks collect, store bio specimens for diagnosis, treatment and research purpose. According to modern bio banking, bio specimens needs to have standard operating procedures to do so. The bio specimen should be kept confidential and anonymous. Do they have an awareness of the role of biobanks? Do they know the concept of consent and implications of retaining specimens in biobanks? This paper evaluates these areas. A cross sectional study was conducted among general public above 18 years of age using convenience sampling. The data was obtained through a questionnaire which was distributed via online using Google forms and assessed the ethical perception of the general public regarding their willingness to donate own biological samples for teaching and research purposes and their awareness and attitude on biobanks. A total of 200 participants were included in the study. 71.4% participants did not have any prior knowledge about biobanks. 59.6% of the participants were willing to donate the biospecimens for advancement in medical research, benefit the society and future generation. 43.8% of respondents emphasised the main discouraging factor in participation in biobank research is that they have fear of sample exploitation. 37.9 percent participants responded that they would like to specify the scope for use when granting permission to use their sample for research. Biobank will advance in medical research only when medical institutes and government bodies’ install privacy, consent laws and initiate lot of awareness programmes to improve public perspectives and knowledge about biobanking. [ABSTRACT FROM AUTHOR]

Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing large national biobanking initiatives. The rise of individual biobanks is paralleled by various networking activities in the field at both the national and international level, such as BBMRI-ERIC in the EU. A significant contribution to population-based biobanking comes from large cohort studies and national repositories, including the United Kingdom Biobank (UKBB), the CONSTANCES project in France, the German National Cohort (NAKO), LifeLines in the Netherlands, FinnGen in Finland, and the All of Us project in the U.S. At the same time, hospital-based biobanking has also gained importance in medical research. We describe some of the scientific questions that can be addressed particularly well by the use of population-based biobanks, including the discovery and calibration of biomarkers and the identification of molecular correlates of health parameters and disease states. Despite the tremendous progress made so far, some major challenges to population-based biobanking still remain, including the need to develop strategies for the long-term sustainability of biobanks, the handling of incidental findings, and the linkage of sample-related and sample-derived data to other relevant resources. [ABSTRACT FROM AUTHOR]

Objective The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations. Materials and Methods We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals. Results PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P  < .05, 74 were nominally replicated and 55 were fully replicated. At P  < 2.68 × 10−5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated. Discussion Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results. Conclusion This study demonstrated the feasibility of studying common exposures using All of Us data. [ABSTRACT FROM AUTHOR]

Context Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. Objective We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. Methods This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate β values and 95% CI. Results After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend <.05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend <.05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (β −0.04; 95% CI −0.08, −0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend <.05), except for FA values in projection fibers. Conclusion These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health. [ABSTRACT FROM AUTHOR]