bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nothing about Us without Us in Precision Medicine: A Call to Reframe Disability Difference in Genetics and Genomics
Authors: Mintz Kevin T. , Stramondo Joseph A. , Tabor Holly K. 
Published: December 2024

AbstractSixty‐one million Americans and approximately a billion people worldwide live with some form of disability that limits one or more major life activities. The field of precision medicine continues to grapple with how to best serve disability communities. In this paper, we suggest that precision medicine faces an ethical tension between its goal to treat or cure disabling conditions and views that consider disability as a marginalized identity. We appeal to the concepts of recognition justice and distributive justice to argue that the ELSI community should take a more proactive role in promoting disability inclusion in precision medicine's practice and research. We also highlight two priorities for the ELSI community moving forward: facilitating greater collaboration between genetics and genomic professionals and disability communities and advocating for inclusive research design and disability accommodations in the research process.
Toward Justice and Community Empowerment in Genomics Studies on Sensitive Traits
Authors: Natri Heini M. , Chapman Carolyn Riley 
Published: December 2024

AbstractCommunity engagement and participatory research have been appropriately employed to increase the relevance, rigor, and acceptability of all types of research, but these approaches may be particularly important in genomics and biomedical research on sensitive traits such as neurodevelopmental, psychiatric, and behavioral ones. Here, we provide an overview of past and ongoing efforts in community engagement in genomics studies and consider successes and opportunities for further improvement. Informed by this knowledge as well as one of the author's experiences, we set out a vision for a more equitable and collaborative genomics where wider communities, including social, ethnic, and other communities that share a particular trait, are included in the research as peers and collaborators, not solely as objects of study.
Accountability for Reasonableness as a Framework for the Promotion of Fair and Equitable Research
Authors: Dupras Charles , Dubé Marie‐Pierre , Gravel Simon , Haidar Hazar 
Published: December 2024

AbstractDespite increased efforts to ensure diversity in genomic research, the exclusion of minority groups from data analyses and publications remains a critical issue. This paper addresses the ethical implications of these exclusions and proposes accountability for reasonableness (A4R) as a framework to promote fairness and equity in research. Originally conceived by Norman Daniels and James Sabin to guide resource allocation in the context of health policy, A4R emphasizes publicity, relevance of reasons, enforcement, and revision as essential for legitimacy and trust in the decision‐making process. The authors argue that A4R is also relevant to resource allocation in research and that, if adequately informed and incentivized by funding agencies, institutional review boards, and scientific journals, researchers are well‐positioned to assess data‐selection justifications. The A4R framework provides a promising foundation for fostering accountability in genomics and other fields, including artificial intelligence, where lack of diversity and pervasive biases threaten equitable benefit sharing.
Can Open Science Advance Health Justice? Genomic Research Dissemination in the Evolving Data‐Sharing Landscape
Authors: Kraft Stephanie A. , Mittendorf Kathleen F. 
Published: December 2024

AbstractScientific data‐sharing and open science initiatives are increasingly important mechanisms for advancing the impact of genomic research. These mechanisms are being implemented as growing attention is paid to the need to improve the inclusion of research participants from marginalized and underrepresented groups. Together, these efforts aim to promote equitable advancements in genomic medicine. However, if not guided by community‐informed protections, these efforts may harm the very participants and communities they aim to benefit. This essay examines potential benefits and harms of open science and explores how to advance a more just vision of open science in genomics. Drawing on relational ethics frameworks, we argue that researchers should consider their obligations to participants as well as the broader communities that are impacted by their research. We propose eight strategies to provide a foundation of practical steps for researchers to reduce the possibility of harms stemming from open science and to work toward genomic justice.
Moving toward Equity through Embedded ELSI Ethnography
Authors: James Jennifer Elyse , Riddle Leslie , Koenig Barbara , Joseph Galen 
Published: December 2024

AbstractThis paper describes the unique values of, challenges within, and opportunities presented by embedded ELSI ethnography. Drawing from our six‐year embedded ELSI study of the WISDOM (Women Informed to Screen Depending on Measures of Risk) trial, we present three examples of the variable ways we engaged with the WISDOM trial's scientific team. WISDOM is a preference‐sensitive, pragmatic, randomized controlled trial of risk‐based breast cancer screening informed by genomics. Our embedded ELSI approach included multiple modes of engagement: (a) Trial investigators sought bioethics expertise; for example, we were asked to consult on traditional bioethics topics such as consent as well as more complex questions about whether to implement a specific risk‐assessment approach on only one race‐defined group of trial participants. (b) As the ELSI investigators, we identified ethical concerns in issues that surfaced via ethnography and considered them in the Bioethics Working Group; for example, there were concerns about the implementation processes that the WISDOM team viewed as logistical challenges. (c) Our presence in WISDOM working group conversations and our expertise on classic social science topics, including race and gender, offered opportunities to engage on the spot with topics such as how to include transgender participants in a trial initially focused on “women's health”; through such engagement, the value of social science became clear to the trial investigators. The paper elaborates on the dynamic relationship between our ethnographic observations, the Bioethics Working Group discussions, and the contributions of each to our real‐time ELSI interventions in these examples. The methods and experiences we describe here suggest modes of engagement that, in combination, have the potential to expand the role of ELSI to offer real‐time intervention on issues related to equity, inclusion, and justice in genetic and genomic research.
From Eugenics to Human Genome Editing: Bionationalism and Instrumentalizing Life in China within a Global Context
Authors: Nie Jing‐Bao 
Published: December 2024

AbstractAs shocking as He Jiankui's genetic experiment resulting in the world's first gene‐edited babies may have been, a socioethical inquiry into this paradigmatic case of scientific misconduct reveals its deep roots in genetic and scientific nationalism, as manifested in the widely accepted practice of yousheng (superior birth or eugenics) in China and the country's authoritarian pursuit of science superpower status. Along with eugenics, bionationalism has long been an international phenomenon. A global sociobioethics or ethical transculturalism is thus necessary to adequately investigate the macrolevel sociopolitical, historical, and transnational forces, such as bionationalism, that structurally shape bioethical issues and people's responses to them, causing the systematic undermining of essential bioethical norms and the instrumentalization of human life.
A Just Genomics Needs an ELSI of Translation
Authors: Halley Meghan C. , Olson Nate W. , Ashley Euan A. , Goldenberg Aaron J. , Tabor Holly K. 
Published: December 2024

AbstractThe rapid advances in genomics over the last decade have come to fruition amid intense public discussions of justice in medicine and health care. While much emphasis has been placed on increasing diversity in genomics research participation, an overly narrow focus on recruitment eschews recognition of the disparities in health care that will ultimately shape access to the benefits of genomic medicine. In this essay, we suggest that achieving a just genomics, both now and in the future, requires an explicit ELSI of translation—normative and pragmatic scholarship that embraces the interconnectedness of research and clinical care and centers the obligations of researchers, institutions, and funders to mitigate inequities throughout the translational pipeline. We propose core principles to guide an ELSI of translation and to ensure that this work balances the value of the generalizable knowledge that genomics research generates and the value of the individuals and communities who make this research possible.
Linking Anxiolytic Action to Hippocampal “Theta”—A Personal History
Authors: McNaughton N. 
Published: December 2024

ABSTRACTThis paper provides a personal history of work starting with the discovery that anxiolytic drugs reduce hippocampal theta frequency. It includes parallel work on septal elicitation of theta carried out in Jeffrey Gray's laboratory in Oxford; a statement of my original scientific perspective on the work; and a description of later work in my laboratory in New Zealand confirming the function of theta rhythmicity per se and its mediation of the effects of anxiolytic drugs on behavior. I finish with comments on risk management with such experiments and their use in larger scale theory development.
The Discovery of Head Direction Cells: A Personal Account
Authors: Taube Jeffrey S. 
Published: December 2024

ABSTRACTThis article is my recollection of events surrounding the discovery of head direction (HD) cells by Jim Ranck in 1984 and the first journal publications 6 years later. Ranck first described the fundamental properties of HD cells qualitatively in a Society for Neuroscience abstract (1984) and in the proceedings to a conference. Ranck, however, was convinced by Bob Muller, a faculty colleague in the lab, to delay writing up Jim's discovery until they developed a two‐spot video tracking system, which would enable proper quantitative analyses. The development of this system was complex and was still undergoing development when I arrived in the Brooklyn lab in 1986. By this time, Jim had begun to refocus his efforts on thinking about the relationship between space and manifolds and was no longer engaged in active research. It thus befell me (unintentionally) to complete the recordings of these fascinating cells. This endeavor involved recording additional HD cells with the new video tracking system, monitoring the cells' responses following a series of environmental manipulations, and performing quantitative analyses on the data. Throughout 1987, I recorded most of the cells that would form the basis for our 1990 papers published in the Journal of Neuroscience. Along the way, there were many events and emotions: luck, excitement, humor, frustration, tutorials, unintended outcomes, and long‐lasting friendships. I was guided and supported during this time by both Bob Muller and John Kubie, but remain forever grateful to Jim for this wonderful opportunity.
Exploration of histone protein γ‐H2AX as a prognostic factor in soft tissue sarcomas and its association with biological behavior, immune cell environment and survival in leiomyosarcoma
Authors: Simon Adrian Georg , Lyu Su Ir , Schultheis Anne Maria , Stahl David , Wuerdemann Nora , Walter Sebastian , Hieggelke Lena , Buettner Reinhard , Bruns Christiane Josephine , Eysel Peer , Schiffmann Lars Mortimer , Knipper Karl , Mallmann Peter , Quaas Alexander , Ullrich Roland 
Published: December 2024

AbstractThis study evaluates the H2AX/γ‐H2AX expression in soft tissue sarcomas (STS), its implications for biological behavior and immune environment, and its potential as a prognostic biomarker. RNA‐Seq data from 237 STS were obtained from The Cancer Genome Atlas project. Patients were stratified by H2AX mRNA expression using a survival‐associated cutoff. Differentially expressed genes and pathways as well as immune signatures between H2AXhigh‐ and H2AXlow tumors were identified with DESeq2 analysis, gene set enrichment analyses (GSEA), Enrichr pathway analysis and CIBERSORTx. Tissue microarrays of a different cohort of 291 STS were generated for immunohistochemical staining to assess γ‐H2AX protein expression, followed by statistical evaluation. High H2AX mRNA expression was associated with shorter overall survival (OS) in STS (p = 0.02), particularly in leiomyosarcomas (LMS) (p < 0.001), and was a negative prognostic factor in LMS (HR 11.15, p < 0.001). H2AXhigh LMS tumors showed upregulation of cell cycle‐related pathways, while H2AXlow LMS exhibited increased inflammatory activity, including elevated M1 macrophage signatures and resting mast cell signatures (both p < 0.001). High γ‐H2AX protein levels were an independent negative prognostic factor in the total LMS cohort (HR 12.12, p = 0.025) and in the subgroup of non‐uterine LMS (HR 153.80, p = 0.013). Consistent with CIBERSORTx analysis, γ‐H2AXlow LMS showed higher mast cell infiltration than γ‐H2AXhigh LMS (p = 0.038). In conclusion, H2AX mRNA and γ‐H2AX protein expression are associated with distinct biological behavior, differences in the immune cell environment, and might serve as useful prognostic biomarkers in LMS.
A Novel Edge‐Enhanced Networks for Optic Disc and Optic Cup Segmentation
Authors: Liu Mingtao , Wang Yunyu , Li Yuxuan , Hu Shunbo , Wang Guodong , Wang Jing 
Published: December 2024

ABSTRACTOptic disc and optic cup segmentation plays a key role in early diagnosis of glaucoma which is a serious eye disease that can cause damage to the optic nerve, retina, and may cause permanent blindness. Deep learning‐based models are used to improve the efficiency and accuracy of fundus image segmentation. However, most approaches currently still have limitations in accurately segmenting optic disc and optic cup, which suffer from the lack of feature abstraction representation and blurring of segmentation in edge regions. This paper proposes a novel edge enhancement network called EE‐TransUNet to tackle this challenge. It incorporates the Cascaded Convolutional Fusion block before each decoder layer. This enhances the abstract representation of features and preserves the information of the original features, thereby improving the model's nonlinear fitting ability. Additionally, the Channel Shuffling Multiple Expansion Fusion block is incorporated into the skip connections of the model. This block enhances the network's ability to perceive and characterize image features, thereby improving segmentation accuracy at the edges of the optic cup and optic disc. We validate the effectiveness of the method by conducting experiments on three publicly available datasets, RIM‐ONE‐v3, REFUGUE and DRISHTI‐GS. The Dice coefficients on the test set are 0.871, 0.9056, 0.9068 for the optic cup region and 0.9721, 0.967, 0.9774 for the optic disc region, respectively. The proposed method achieves competitive results compared to other state‐of‐the‐art methods. Our code is available at: https://github.com/wangyunyuwyy/EE‐TransUNet.
Applying Bayesian Networks to TRL Assessments – Innovation in Systems Engineering
Authors: Austin Marc F. , Ahalt Virginia , Doolittle Erin , Homberger Cheyne , Polacek George A. , York Donal M. 
Published: December 2024

ABSTRACTCurrently, technology readiness assessments (TRAs) are used in determining the maturity of the critical technology elements (CTEs) of a system as it moves forward in the system development life cycle. The TRA method uses technology readiness levels (TRLs) as the decision metric. TRL values are assessed and determined by subject matter experts (SMEs). Since expert evaluators often differ in their judgment when scoring a system element against the TRL scale criteria, this paper argues for the use of a Bayesian network model to provide a mathematical method to consistently combine and validate the judgment of these SMEs and increase the confidence in the determination of the readiness of system components and their technologies.
A Bayesian Approach for Estimating Complex System Reliability
Authors: Doguc Ozge , Ramirez‐Marquez Jose Emmanuel 
Published: December 2024

ABSTRACTAlthough a number of recent studies on using Bayesian Networks (BN) for system reliability estimation have been proposed, these studies are based on the assumption that a pre‐built BN was designed to represent the system. In these studies, the task of building the BN is typically left to a group of specialists who are BN and domain experts. However, the process of building a system‐specific BN is generally very time consuming and may lead to incorrect deductions. As there are no existing studies to eliminate the need for a human expert in the process of system reliability estimation, this paper introduces a holistic method that uses historical data about the system to be modeled as a BN and provides efficient techniques for automated construction of the BN model and estimation of the system reliability. Moreover, very limited human intervention is sufficient for the process of BN construction and reliability estimation.
Chaperone Proteins: The Rising Players in Muscle Atrophy
Authors: Acquarone Davide , Bertero Alessandro , Brancaccio Mara , Sorge Matteo 
Published: December 2024

ABSTRACTDespite significant progress in understanding the molecular aetiology of muscle atrophy, there is still a great need for new targets and drugs capable of counteracting muscle wasting. The role of an impaired proteostasis as the underlying causal mechanism of muscle atrophy is a well‐established concept. From the earliest work on muscle atrophy and the identification of the first atrogenes, the hyper‐activation of the proteolytic systems, such as autophagy and the ubiquitin proteasome system, has been recognized as the major driver of atrophy. However, the role of other key regulators of proteostasis, the chaperone proteins, has been largely overlooked. Chaperone proteins play a pivotal role in protein folding and in preventing the aggregation of misfolded proteins. Indeed, some chaperones, such as αB‐crystallin and Hsp25, are involved in compensatory responses aimed at counteracting protein aggregation during sarcopenia. Chaperones also regulate different intracellular signalling pathways crucial for atrogene expression and the control of protein catabolism, such as the AKT and NF‐kB pathways, which are regulated by Hsp70 and Hsp90. Furthermore, the downregulation of certain chaperones causes severe muscle wasting per se and experimental strategies aimed at preventing this downregulation have shown promising results in mitigating or reversing muscle atrophy. This highlights the therapeutic potential of targeting chaperones and confirms their crucial anti‐atrophic functions. In this review, we summarize the most relevant data showing the modulation and the causative role of chaperone proteins in different types of skeletal muscle atrophies.
Beyond the income‐achievement gap: The role of individual, family, and environmental factors in cognitive resilience among low‐income youth
Authors: Rakesh Divyangana , Sadikova Ekaterina , McLaughlin Katie A. 
Published: December 2024

AbstractBackgroundLow socioeconomic status is associated with lower cognitive performance and long‐term disparities in achievement and success. However, not all children from low‐income backgrounds exhibit lower cognitive performance. Characterizing the factors that promote such resilience in youth from low‐income households is of crucial importance.MethodsWe used baseline data from participants in the lowest tertile of income‐to‐needs in the Adolescent Brain Cognitive Development study and machine learning to identify the factors that predict fluid and crystallized cognitive resilience among youth from low‐income backgrounds. Predictors included 164 variables across child characteristics, family and developmental history, and environment.ResultsOur models were reliably able to predict resilience but were substantially more accurate for crystallized cognition (AUC = 0.75) than for fluid cognition (AUC = 0.67). Key predictors included developmental factors such as birthweight and duration of breastfeeding, neighborhood‐level factors (e.g., living in concentrated privilege, enrollment in advanced placement courses), children's own temperament and mental health, and other factors such as physical activity and involvement in extracurricular activities.ConclusionOur findings highlight the importance of a multifaceted approach to promoting cognitive resilience among children from low‐income households in future intervention work.
Factors related to mean corpuscular volume in HFE p.C282Y homozygotes
Authors: Barton James C. , Barton J. Clayborn , Acton Ronald T. 
Published: December 2024

AbstractIntroductionThe aim of this study was to define the relationships between factors other than transferrin saturation (TS) to mean corpuscular volume (MCV) and macrocytosis (MCV > 100 fL) in HFE p.C282Y (rs1800562) homozygotes.MethodsWe studied white post‐screening participants with p.C282Y homozygosity who did not have anemia, report cirrhosis or pregnancy, or use medications that increase MCV. We analyzed relations of MCV and macrocytosis with age, sex, diabetes reports, daily alcohol consumption, swollen or tender 2nd/3rd metacarpophalangeal (MCP) joints, TS, and serum ferritin (SF).ResultsThere were 257 participants (110 men and 147 women). Median alcohol consumption, median TS, median SF, and macrocytosis prevalence were significantly greater in men. Relative risk of macrocytosis in men was 2.81. In men and women, there were significant positive Pearson's correlations of MCV versus age and Spearman's correlations of MCV versus alcohol consumption and TS. Mean MCV and macrocytosis prevalence were significantly greater in participants with than without swollen or tender 2nd/3rd MCP joints. Linear regression on MCV revealed positive associations: age (p < 0.0001), alcohol consumption (p = 0.0007), and TS (p < 0.0001). Logistic regression on macrocytosis revealed an odds ratio for age of 1.04 (95% confidence interval: 1.00, 1.07).ConclusionsMCV in HFE p.C282Y homozygotes is positively related to age, daily alcohol consumption, TS, and swollen or tender 2nd/3rd MCP joints.