Digital Commons Network^™

Glutamatergic Lateral Habenula Neurons Modulate Consolidation Of Associative Memories, Snigdha Srivastava, I-Ching Wang, Mikhail Y Kochukov, Jessica L Swanson, Mauro Costa-Mattioli, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

INTRODUCTION: Despite the rise in psychiatric disorders worldwide, the underlying brain circuits responsible for these devastating conditions remain elusive. The lateral habenula (LHb) has emerged as a key brain structure in depression studies due to its hyperactive state in both patients and animal models. While this aligns with known roles in driving aversive states and regulating serotonin release, it is still unclear how acute and transient activity changes in the LHb can influence higher order cognitive processes such as learning, memory, and behavioral adaptation. Given the importance of these processes to psychiatric conditions, understanding how LHb activity impacts cognitive function …

Resort Enhances Reference-Based Cell Type Deconvolution For Spatial Transcriptomics Through Regional Information Integration, Linhua Wang, Ling Wu, Guantong Qi, Chaozhong Liu, Wanli Wang, Xiang H-F Zhang, Zhandong Liu

Duncan NRI Faculty and Staff Publications

Motivation: Spatial transcriptomics (ST) captures positional gene expression within tissues but lacks single-cell resolution. Reference-based cell type deconvolution methods were developed to understand cell type distributions for ST. However, batch/platform discrepancies between references and ST impact their accuracy.

Results: We present Region-based Cell Sorting (ReSort), which utilizes ST's region-level data to lessen reliance on reference data and alleviate these technical issues. In simulation studies, ReSort enhances reference-based deconvolution methods. Applying ReSort to a mouse breast cancer model highlights macrophages M0 and M2 enrichment in the epithelial clone, revealing insights into epithelial-mesenchymal transition and immune infiltration.

Availability and implementation: Source codes …

Survey And Improvement Strategies For Gene Prioritization With Large Language Models, Matthew B Neeley, Guantong Qi, Guanchu Wang, Ruixiang Tang, Dongxue Mao, Chaozhong Liu, Sasidhar Pasupuleti, Bo Yuan, Fan Xia, Pengfei Liu, Zhandong Liu, Xia Hu

Duncan NRI Faculty and Staff Publications

Motivation: Rare diseases remain difficult to diagnose due to limited patient data and genetic diversity, with many cases remaining undiagnosed despite advances in variant prioritization tools. While large language models have shown promise in medical applications, their optimal application for trustworthy and accurate gene prioritization downstream of modern prioritization tools has not been systematically evaluated.

Results: We benchmarked various language models for gene prioritization using multi-agent and Human Phenotype Ontology classification approaches to categorize patient cases by phenotype-based solvability levels. To address language model limitations in ranking large gene sets, we implemented a divide-and-conquer strategy with mini-batching and token limiting …

Talking About Suffering In The Intensive Care Unit, Brent M Kious, Judith B Vick, Peter A Ubel, Olivia Sutton, Jennifer Blumenthal-Barby, Christopher E Cox, Deepshikha Ashana

Center for Medical Ethics and Health Policy Staff Publications

Background: Some have hypothesized that talk about suffering can be used by clinicians to motivate difficult decisions, especially to argue for reducing treatment at the end of life. We examined how talk about suffering is related to decision-making for critically ill patients, by evaluating transcripts of conversations between clinicians and patients' families.

Methods: We conducted a secondary qualitative content analysis of audio-recorded family meetings from a multicenter trial conducted in the adult intensive care units of five hospitals from 2012-2017 to look at how the term "suffering" and its variants were used. A coding guide was developed by consensus-oriented discussion …

A Hybrid Cloud Data Lake Architecture Supporting The Integration Of Clinical And Genomics Data, Apollo Mcowiti, Heidi Dowst, Fei Zheng, Susan Hilsenbeck, Christopher Amos

Center for Medical Ethics and Health Policy Staff Publications

Objective: Cancer centers must quickly integrate clinical genomics data from different vendors for oncology operations and research. Clinical data warehouse architectures are costly to construct and brittle, and they are not readily amenable to the rapid changes in oncology research. We introduce a cost-effective hybrid cloud Data Lake architecture for storing clinical genomic data from different vendors, aiding both clinical and research workflows.

Methods: We created a Data Lake architecture based on the zone architecture, with four layers: ingestion, storage, transformation, and interaction. The layers are implemented with a hybrid cloud architecture. Rich metadata created from patient and genomic data …

Different Responses Involving Tfh Cells Delay Parasite-Specific Antibody Production In Trypanosoma Cruzi Acute Experimental Models, Ana Carolina Leão, Maria Jose Villar, Rakesh Adhikari, Cristina Poveda, Leroy Versteeg, Gregório Almeida, Peter J Hotez, Maria Elena Bottazzi, Kathryn M Jones

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Chagas disease (CD), caused by the parasite Trypanosoma cruzi, affects millions globally. Despite treatment options in the acute phase, most infections progress to a chronic indeterminate form or develop severe cardiac/gastrointestinal complications. Understanding the immune response is crucial for the development of vaccines and more efficient drugs for the disease control.

Methods: This work investigates the immune response to T. cruzi H1 K68 strain infection in female BALB/c and C57BL/6 mice to characterize differences in Tfh and B cell responses that may be involved in the poor parasite-specific antibody production during acute infection. For this, mice were euthanized …

When Families Bridge The Research-Clinical Divide: An Exploration Of Values Regarding Cascade Screening In Genomic Research, Katherine E Bonini, Lauren R Desrosiers-Battu, Ann Katherine M Foreman, Nuriye N Sahin-Hodoglugil, Mary A Majumder, Candice R Finnila, Stephanie A Kraft, Laura M Amendola, Eimear E Kenny, Stephanie M Fullerton, Sara L Ackerman, Benjamin S Wilfond, Amy L Mcguire, Hadley Stevens Smith

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Genetic results are important for both patients and their biological relatives. However, cascade screening (CS) uptake is low, especially when testing occurs through research programs and not clinical care. Ethical guidance is needed for CS implementation when individuals receive clinical genetic results through research.

Methods: We conducted focus groups with 3 groups of individuals in the Clinical Sequencing Evidence-Generating Research Consortium: clinicians, patient representatives, and scholars of the ethical, legal, and social implications of genomics. We used inductive thematic and comparative analyses to analyze data within and across the groups.

Results: All participants (n = 27) agreed that …

Advancing Medical Applications Of Cancer Nanotechnology: Highlighting Two Decades Of The Nci's Nanotechnology Characterization Laboratory Service To The Research Community, Rachael M Crist, Yechezkel Barenholz, Ahuva Cern, Kate N Clark, Pieter R Cullis, Cheryl Dean, Neil Desai, Mauro Ferrari, Matthieu Germain, Carmen A Giacomantonio, Emma Grabarnik, Piotr Grodzinski, Atara Hod, Barry E Kennedy, Ruvanthi N Kularatne, Glen S Kwon, Emmanuel Loeb, Erin B Noftall, Len Pagliaro, Morteza Rasoulianboroujeni, Alexander Roth, Darren Rowles, Kulbir Singh, Nicole F Steinmetz, Zhanna Yehtina, Yao Zhang, Daniel Zilbersheid, Jeffrey D Clogston, Stephan T Stern, Marina A Dobrovolskaia

Center for Medical Ethics and Health Policy Staff Publications

The Nanotechnology Characterization Laboratory (NCL) is a US federally funded resource providing characterization and expertise to the cancer nanomedicine research community. Founded as a formal partnership among the US National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the US National Institute of Standards and Technology (NIST), the NCL has spent two decades developing a one-of-a-kind service with broad multidisciplinary expertise to meet the needs of a rapidly evolving drug development field. To mark the 20th anniversary of the lab's founding, the NCL hosted a symposium to highlight the achievements of the cancer nanomedicine field, showcase novel, …

Deep Brain Stimulation For Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views On Candidacy Factors, Ilona Cenolli, Tiffany A Campbell, Natalie Dorfman, Meghan Hurley, Jared N Smith, Kristin Kostick-Quenet, Eric A Storch, Jennifer Blumenthal-Barby, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS.

Objectives: …

Thermal Regimes Of Beaver-Impacted Stream Reaches In The Tualatin River Basin, Oregon, United States, Miles Mayer, Heejun Chang

Geography Faculty Publications and Presentations

As beavers are increasingly used in stream restoration, interest in their potential to mitigate stream degradation has grown. However, the impacts of beaver dams on stream temperature remain inconsistent across studies, often due to differences in spatial scale and methodology. We investigated summer thermal regimes at multiple spatial scales in three beaver-impacted streams within the Tualatin River Basin, Oregon, using fiber-optic distributed temperature sensing. Substantial variability in thermal regimes was observed among the three stream reaches and around individual beaver dams within each reach. This variability was primarily influenced by geomorphic changes in stream depth associated with beaver dams and …

Collaborative Governance And Hydrosocial Territorialization: Reaching Consensus On Salmon Restoration Goals In The Columbia River Basin, Thien-Kim Bui, Rebecca Mclain

Geography Faculty Publications and Presentations

Across the Cascadia bioregion, salmon and steelhead are ecological and cultural keystone species that contribute to and illustrate riverine health. Due to complex social, economic, and ecological relations over the past 150 years, many Columbia River Basin salmon and steelhead populations are now listed as threatened or endangered in the United States. This research uses the 2017–2020 Columbia Basin Partnership Task Force as a case study to understand how this collaborative governance effort of sovereign entities and nonsovereign stakeholders navigated competing water claims to reach consensus on aspirational qualitative and quantitative goals for salmon and steelhead restoration. Using semistructured interviews …

Do Academic Researchers Care About Patent Infringement? A Pcr Case Study, Janet Freilich

Faculty Scholarship

Because much cutting-edge academic research involves building on other new technologies, university research often involves making or using a patented invention—an act of patent infringement. The problem of how patents affect academic researchers has attracted considerable attention, but legal scholars are divided on the magnitude of patents’ potential impact. Many scholars fear that patents will entirely hobble academic scientific research, while others find that academic researchers entirely ignore patents and thus that they have little impact. This Article adds a piece of empirical evidence to the debate by studying the example of polymerase chain reaction (PCR) technology. In the early …

Evidence-Based Evaluation To Promote High-Value Care In Pediatric Critical Care: It Is Time To Fully Adopt, Maya Dewan, Rajit K Basu, Erin Bennett, Lily B Glater-Welt, Mark Hall, Benson S Hsu, Lia Lowrie, Venessa Lynn Pinto, Alexandre T Rotta, Edward Seferian, Linda Siegel, Heather A Wolfe, Vijay Srinivasan

Faculty, Staff and Students Publications

Introduction: Evidence-based recommendations for high-value care in pediatric critical care are needed. We sought to develop recommendations to identify unnecessary interventions, enhance outcomes, and promote efficient, patient-centered practices.

Methods: Using a modified Delphi process, a multi-institutional panel of pediatric intensivists from a national pediatric critical care quality improvement group identified 30 potential topics and selected 20 high- and medium-priority topics for further evaluation, and narrowed them to 10 by consensus voting. A structured scoping review of literature published between 2014 and 2023 identified 10 practices, which were critically assessed using the PICOST framework. The panel selected 5 priority recommendations based …

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

Refinement Of A Published Gene-Physical Activity Interaction Impacting Hdl-Cholesterol: Role Of Sex And Lipoprotein Subfractions, Kenneth E Westerman, Tuomas O Kilpeläinen, Magdalena Sevilla-Gonzalez, Margery A Connelly, Alexis C Wood, Michael Y Tsai, Kent D Taylor, Stephen S Rich, Jerome I Rotter, James D Otvos, Amy R Bentley, Samia Mora, Hugues Aschard, D C Rao, Charles Gu, Daniel I Chasman, Alisa K Manning

Faculty, Staff and Students Publications

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C). We explored this GxE in the Women’s Genome Health Study (WGHS; N=23,294; the strongest cohort-specific signal in the original meta-analysis), the UK …

Normalizing Facial Recognition Technology And The End Of Obscurity, Woodrow Hartzog, Evan Selinger, Judy Hyojoo Rhee

Faculty Scholarship

This article argues that facial recognition technology is the most dangerous surveillance tool ever invented. Given the unique threats this morally suspect tool poses to privacy, civil liberties, human flourishing, and democracy, the only appropriate response is a ban. To justify our position, we explain why facial recognition is distinctive among biometrics, clarify how even seemingly benign and positive uses of the technology can trigger dangerous normalization dynamics, and pinpoint why current United States laws (with reverberations in the EU’s AI Act) are designed to accelerate a slippery slope that makes mass surveillance nearly inevitable. Our most fundamental contribution lies …

Policing Gender: The Interest Convergence Of Women's And Transgender Rights, Michael Ulrich

Faculty Scholarship

The social, political, and legal landscape has seen a resurgence of gender fundamentalism, seeking to reinforce archaic notions of what it means to be a woman. Social media movements run in tandem with this resurgence of gender fundamentalism. For instance, the “tradwife” phenomenon that romanticizes a domestic, subservient role for women.¹ Alabama Senator Katie Britt most infamously reflected the convergence of these trends when she delivered her response to the State of the Union from a kitchen table and proclaimed that her message was “a direct appeal” to her “fellow moms.”² Meanwhile, executive orders and state laws have …

Ten Tips For Legal Empiricists, Jordana Goodman, Christa J. Laser, Mark A. Lemley, Lisa Larrimore Ouellette, Melissa F. Wasserman, Saurabh Vishnubhakat, Janet Freilich, Jessica Silbey, David L. Schwartz, Neel U. Sukhatme

Faculty Scholarship

This essay offers practical tips from leading legal empirical researchers to assist new scholars who are entering the field. Topics include developing meaningful research questions, designing robust survey methodologies, balancing qualitative and quantitative approaches, ensuring data transparency, fostering interdisciplinary collaboration, and navigating ethical considerations in empirical work. Drawing from their own unique challenges and successes, scholars Michael D. Frakes, Janet Freilich, Mark A. Lemley, Lisa Larrimore Ouellette, David L. Schwartz, Jessica Silbey, Neel U. Sukhatme, Saurabh Vishnubhakat, Melissa F. Wasserman, Jordana Goodman, and Christa Laser illuminate what they wished they would have known going into empirical research and the pitfalls …

Challenging The Law, Steven Arrigg Koh

Faculty Scholarship

Frédéric Mégret’s engaging contribution, A Look Back at The Women’s Hague Peace Conference: What Contribution To International Law Today?, exposes a legal duality. On one hand, the legalist perspective: law is a closed system. From this perspective, law is objective, hard, universal, and bounded. On the other hand, the sociocultural perspective: law is a human practice. From this perspective, law is subjective, organic, particular, and porous. This Essay reads Mégret’s analysis of the 1915 International Congress of Women in The Hague as a “sociocultural challenge,” disrupting the legalist perspective on international law, war, and peace during World War I. …

Under What Circumstances Is "Caste" Likely To Be Useful As An Analytic Concept (And Should We Care)?, Sanford V. Levinson, Robert L. Tsai

Faculty Scholarship

This Essay is the product of the 2025 “Constitutional Law Schmooze,” where academics from a variety of disciplines and from all over the country meet to discuss a common topic of constitutional law chosen by the moderator. This year’s topic was “caste.” The two of us, having written independent “tickets” of admission for the schmooze—i.e., short essays setting out our tentative thoughts about “caste”—turned out to be relative skeptics about the value of the term for lawyers. We are certainly not hostile to those who differ with us. This should be regarded as a “friendly dissent,” as distinguished, say, from …

What We Should Know About The Reliability Of Empirical Legal Studies, Kathryn Zeiler

Faculty Scholarship

The findings of replication studies conducted in the early 2010s led many to declare that science was in the midst of a “replication crisis.” Since then, a growing number of reforms have been proposed and tested. The field of empirical legal studies seems behind other fields such as psychology, economics, political science, medicine, biology, and others that have taken significant steps toward uncovering the general reliability of the field’s empirical work, investigating the causes of observed unreliability, and instituting and testing the effects of various reforms. The purpose of this Article is to summarize what we know about the reliability …

The Complex Development Of Psoralen-Interstrand Crosslink Resistance In Escherichia Coli Requires Acrr Inactivation, Retention Of A MarboxSequence, And One 3 Of Three Mara, Soxs, Or Rob Global Regulators, Travis K. Worley, Ayah H. Asal, Lo Cooper, Charmain T. Courcelle, Justin C. Courcelle

Biology Faculty Publications and Presentations

Crosslinking agents, such as psoralen and UVA radiation, can be effectively used as antimicrobials and for treating several dysplastic conditions in humans, including some cancers. Yet, both cancer cells and bacteria can become resistant to these compounds, making it important to understand how resistance develops. Recently, several mutants were isolated that developed high-levels of resistance to these compounds through upregulation of components of the AcrAB-TolC-efflux pump. Here, we characterized these mutants and found that resistance specifically requires inactivating mutations of the acrR transcriptional repressor which also retain the marbox sequence found within this coding region. In addition, the …

Heterospecific Coprophagy In The White-Tailed Deer Odocoileus Virginianus (Zimmermann, 1780) In Costa Rica, Mora Manuel Jose, Juan De Dios Astorga-Acuña

Biology Faculty Publications and Presentations

Animals may engage in coprophagy, including heterospecific coprophagy, where they consume the feces of other species. The white-tailed deer, Odocoileus virginianus, primarily feeds on plant material, such as tender forbs and shrub shoots. This report documents a case of heterospecific coprophagy by the white-tailed deer in Costa Rica, where two individuals were observed consuming domestic horse feces. The reasons for heterospecific coprophagy in ruminants like the white-tailed deer are unclear. Nutritional supplementation, microbial transfer, or other ecological factors may play a role in this behavior. However, such a behavior also poses risks, including the transmission of diseases and parasites from …