Digital Commons Network^™

Morphology-Aware Hrv Estimation From Wrist Ppg In Sedentary Scenarios, Changshuo Hu, Hung Manh Pham, Dong Ma

Research Collection School Of Computing and Information Systems

Photoplethysmography (PPG) is widely used in wearable devices for non-invasive heart rate variability (HRV) monitoring. While most prior work focuses on mitigating motion artifacts, recent studies highlight that even subtle contact pressure variations can distort waveform morphology and lead to inaccurate HRV estimates. In this work, we propose a morphology-aware deep learning framework that conditions HRV estimation on beat-level waveform types. Our model jointly encodes the raw PPG waveform and a sequence of pressure-induced morphology labels using parallel encoders, integrates them via cross-attention, and predicts normal-to-normal (NN) intervals and beat count to support downstream HRV computation. Evaluated on the public …

Cross-Subject Mind Decoding From Inaccurate Representations, Yangyang Xu, Bangzhen Liu, Wenqi Shao, Yong Du, Shengfeng He, Tingting Zhu

Research Collection School Of Computing and Information Systems

Decoding stimulus images from fMRI signals has advanced with pre-trained generative models. However, existing methods struggle with cross-subject mappings due to cognitive variability and subject-specific differences. This challenge arises from sequential errors, where unidirectional mappings generate partially inaccurate representations that, when fed into diffusion models, accumulate errors and degrade reconstruction fidelity. To address this, we propose the Bidirectional Autoencoder Intertwining framework for accurate decoded representation prediction. Our approach unifies multiple subjects through a Subject Bias Modulation Module while leveraging bidirectional mapping to better capture data distributions for precise representation prediction. To further enhance fidelity when decoding representations into stimulus images, …

Memad: Structured Memory Of Debates For Enhanced Multi-Agent Reasoning, Shuai Ling, Lizi Liao, Dongmei Jiang, Weili Guan

Research Collection School Of Computing and Information Systems

Large Language Models (LLMs) demonstrate remarkable in-context learning capabilities but often struggle with complex, multi-step reasoning. Multi-Agent Debate (MAD) frameworks partially address these limitations by enabling iterative agent interactions. However, they neglect valuable historical insights by treating each new debate independently. In this paper, we propose Memory-Augmented MAD (MeMAD), a parameter-free memory-augmented MAD framework that systematically organizes and reuses past debate transcripts. MeMAD stores structured representations of successful and unsuccessful reasoning attempts enriched with self-reflections and peer feedback. It systematically retrieves them via semantic similarity at inference time to inform new reasoning tasks. Our experiments on challenging mathematical reasoning, scientific …

Institute For Global Health And Development : Issue 12 - October 2025, Institute For Global Health And Development

IGHD Newsletters

• Dr. Bhutta Awarded the Virchow Prize 2025 For Global Health
• Mapping Climate Vulnerability and Resilience Across the Prepare Pakistan Project – Promoting Climate Resilience, Pakistan’s High-Risk Districts
• Choice Project Dissemination Workshop Held in Accelerating Progress Towards Health and Health-Related SDGS Nairobi
• Farhana Tabassum Attends the Inauguration Of “Imagining Life” At the Climate Action Center, Karachi
• IGHD Participates in the Green Zameen Fellowship on Sustainable Energy Transition
• IGHD Team Leads Systematic Reviews & Meta-Analysis
• Empowering Research in Maternal Health Dr. Khadija Vadsaria Completes Her PhD at Aga Khan University
• Climate Change and Maternal Health Dr. Jai Das Featured in the Economist …

Check Out The Library, 2025 Fall Issue, Cal Poly Humboldt Library

Library Publications

Issue 20

Analyzing Sea Level Rise Scenarios Impact On The Mobility, Infrastructures, Environment Of Abu Dhabi And Defining Solutions By Creating A Digital Twin Using Gis And Game Engine, Justine Sylviane Lucie Sarrau

Dissertations

This dissertation investigates the potential impact of future sea level rise (SLR) scenarios on the city of Abu Dhabi. With climate change, many coastal towns are at risk of experiencing this type of natural hazard. Currently, no precise scenario simulations have been developed, mainly due to the use of low spatial resolution elevation data. Additionally, the difficulty in understanding the real impacts persists when analyses rely solely on traditional cartography and GIS methods. This dissertation aims to advance the field by offering a new approach, which involves creating a comprehensive dynamic 3D simulation with dynamic flowing water. This model, defined …

Irf6 Regulates Adherens Junction Proteins And Inflammatory Cytokines In Salivary Acinar Cells And Its Expression Is Elevated In Sjӧgren’S Syndrome, Vi Pham, Antonio Hernandes Chaves Neto, Julia Zheng, Mary Elmeniawi, Krishna Kumar Kookal, Muhammad F Walji, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates. At the molecular level, the acinar differentiation markers E-cadherin and MIST1 were markedly reduced in Irf6-null embryonic SG, while the proinflammatory cytokines, …

Vegetation Dynamics And Land-Use History During The Holocene In Corsica (Western Mediterranean): Regional Patterns And Local Landscape Transformation In Changing Coastal Ecosystems, Jordi Revelles, Ralph Fyfe, Matthieu Ghilardi, Andrés Currás, Federico Di Rita

School of Geography, Earth and Environmental Sciences

The archaeoecological research conducted in Corsica underscores the critical role of integrating palynological studies from sedimentary deposits to reconstruct past human-environment interactions. This approach sheds new light on evidence of farming activities and redefines archaeological territories and human occupation temporalities. Understanding the influence of human activities on coastal ecosystems requires outlining natural and climatic dynamics at a regional scale while evaluating landscape transformations at local scale, where human imprints are clearly evidenced. To achieve this, we applied quantitative methodologies to disentangle regional pollen loading from local vegetation signals. The Landscape Reconstruction Algorithm (LRA) was employed as an advanced tool to …

“He’S Here, He’S Not Queer”: The Indexical Potential Of Pronoun Use On American Drag Reality Television, Finn Verdonk , '26

Senior Theses, Projects, and Awards

When English speakers talk about drag performers, what factors impact the pronoun that is used? Pulling data from two seasons of RuPaul’s Drag Race (Season 4 and Season 14) and one season of Dragula (Season 5), this thesis attempts to understand the ways in which drag performers use pronouns in discourse about fellow drag performers. Building from Myers’s 2018 proposal that using he/him pronouns for drag queens can index shadiness or criticism, I expand her sample to see if her findings hold up over time and across franchises. I find that he/him pronouns on RPDR no longer index shadiness and …

Ten Tips For Legal Empiricists, Jordana R. Goodman, Christa J. Laser

Northwestern Journal of Technology and Intellectual Property

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, these scholars illuminate what they wished they would have known going into empirical research and the pitfalls to avoid.

Although many examples focus on intellectual property law, the principles outlined here are broadly applicable to all legal empirical scholarship. This essay aims to serve as …

Unregulated And Unacceptable: Facial Recognition Technology's History, Privacy Concerns, And Impact On Society, Alyssa Pequignot

Northwestern Journal of Technology and Intellectual Property

This Note provides a general review of the current state of Facial Recognition Technology (FRT), including Illinois state regulation and past federal regulation attempts. This Note asserts that even as datasets become more diverse and “fairer,” FRT may still have discriminatory impacts on minority populations, as evidenced by a few highlighted examples that focus on race and gender. This Note suggests that one option to mitigate these dangers is to implement national regulations for its use. Ultimately, this Note suggests what a federal regulation might look like, informed by the societal impacts discussion.

After an introduction in Section I, Section …

Divergent Sensory Transcriptomic Profiles In Positive And Negative Learning In Bicyclus Anynana Butterflies, Yi Ting Ter, Erica L. Westerman

Biological Sciences Faculty Publications and Presentations

Mate preference learning, where individuals learn to prefer or avoid specific phenotypes during mate selection, is pervasive across animal taxa and influences reproductive isolation and trait evolution. Despite its significance, the genetic basis underlying the associated valence attribution (whether to prefer or avoid) remains largely unclear. Both in terms of what genes are associated with attributing valence, and whether valence attribution is associated with transcriptional changes in both sensory tissues and neural circuits in the brain, or is restricted to the brain. Here, we investigate the neurogenomic basis of positive and negative mate preference learning using Bicyclus anynana butterflies. We …

Structure-Activity Relationships Of A–And B-Type Proanthocyanidins In Long-Term Dentin Biomodification And Biocompatibility, Yvette Alania, Mariana Reis-Havlat, Shu-Xi Jing, Fahimeh Tabatabaei, James B. Mcalpine, Shao-Nong Chen, Guido F. Pauli, Ana K. Bedran-Russo

School of Dentistry Faculty Research and Publications

Objective

To explore the structure-activity relationships of plant-based proanthocyanidins (PACs) with dental pulp stem cells (DPSCs) and the long-term biomechanical stability of PAC-modified dentin extracellular matrix (ECM).

Methods

Mid-coronal dentin ECM (n= 8) was treated with eight PAC tetramers and trimers with varying A-/B-type linkages. Chemo-mechanical analyses included dynamic mechanical analysis and ATR-FTIR spectroscopy. Viscoelastic components were calculated after PAC biomodification, 18-month incubation, and protein destabilization. Collagen structure was assessed via IR amide absorbance ratios. DPSCs were cultured with PACs at different concentrations (100, 10, and 1 μg/mL) to measure proliferation. ANOVA and post-hoc tests were used for …

Population Health And Systems Science: Medical Student Feedback On A Novel Approach That Follows A National Curricular Framework, Jeffrey Levin, Gary Beck Dallaghan, Chaynee Atwood, Vanessa Casanova, Cynthia Ball, Theresa Byrd, Emmanuel Elueze, Michael Kennedy, Dalia Nessim, Peter Pendegrass, Yordanos Tiruneh

School of Medicine Faculty Publications and Presentations

Introduction: Population Health and System Science, a longitudinal course at a new medical school in northeast Texas, incorporates case-based learning and experiential field visits during an 18-month pre-clerkship phase. The course integrates content from public and population health, preventive medicine disciplines, and health administration and leadership. Materials and Methods: A cross-sectional survey assessed student self-reports on achievement of session objectives and introduction to national core curricular, cross-cutting, and systems thinking domains. Results: Of 36 students, 33 responded. Most rated objectives favorably. Open-ended responses highlighted relevance to future practice and requested more content on biostatistics, epidemiology, health equity, and healthcare economics, …

Transcript Diversity In Aging: Cryptic Transcription And Splicing, Brenna S Mccauley, Nicholas Nikoloutsos, Weiwei Dang

Faculty, Staff and Students Publications

Increased transcript diversity, which is caused in part by alternative splicing and cryptic transcription, is an underappreciated aspect of age-associated transcriptome remodeling. Recent work has revealed that structurally novel transcripts increase during aging in many tissues. Genes with cryptic and alternatively spliced transcripts with age are enriched for functional categories relevant to tissue function and aging, and have been implicated in cognitive decline, decreased muscle strength, reduced oocyte quality, immune aging, altered stem cell properties, and senescence. Indeed, there is emerging evidence that alternatively spliced transcripts and elevated cryptic transcription directly contribute to aging phenotypes in multiple tissues. The full …

Phosphorylation At Serine 214 Correlates With Tau Seeding Activity In An Age-Dependent Manner In Two Mouse Models For Tauopathies And Is Required For Tau Transsynaptic Propagation, Pablo Martinez, Nur Jury-Garfe, Henika Patel, Yanwen You, Abigail Perkins, Yingjian You, Audrey Lee-Gosselin, Ruben Vidal, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Background

Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely understood.

Objective

To characterize the temporal dynamics of tau seeding activity and identify specific phosphorylated tau species associated with tau propagation in vivo.

Methods

We profiled tau seeding activity using a FRET-based biosensor cell line and correlated it with the abundance of phospho- and conformational tau species in two transgenic mouse models of tauopathy (P301S-1N4R and P301S-0N4R). Immunohistochemistry and subcellular fractionation were used to examine the spatial distribution of tau species. Functional …

Aging Affects Lipid Homeostasis In Lacrimal Glands By Upregulating Lipogenesis And Changing Its Specificity, Seher Yuksel, Prashant Kumar, Sydney E Krenz, Kaitlin K Scholand, Zhiyuan Yu, Anastasiia Ivanova, Helen P Makarenkova, Sarah F Hamm-Alvarez, Igor A Butovich, Cintia S De Paiva

Faculty, Staff and Students Publications

Purpose: The lacrimal gland (LG) develops age-related alterations. This study investigated the lipid content of the accumulated secretions within the murine aged LG.

Methods: C57BL/6J animals of different ages (3 months, 12 months, and 20-26 months) were used. Published data of bulk RNA sequencing of aged LGs were used to investigate lipid pathways. Exorbital LGs were excised for histology or PCR. Histologic sections were stained with standard histochemical stains or immunostained using anti-adiponectin, anti-perilipin 2 antibodies, and BODIPY dye. LG lipidomes were investigated using unbiased, untargeted high-resolution liquid chromatography/mass spectrometry (LC/MS), and the data were processed using unbiased, untargeted principal …

Critical Care Of The Adult With Congenital Heart Disease, Christopher W Valle, Amanda C Garfinkel, Jonathan Buber, Anitra W Romfh, Andrea M Elliott, Jonathan N Menachem, Jennifer Nelson, Peter C Laussen, Jane Heggie, Cameron Dezfulian, David Morrow, Anne Marie Valente, American College Of Cardiology Critical Care Cardiology Section And Adult Congenital And Pediatric Cardiology Section

Faculty, Staff and Students Publications

Advances in the treatment of congenital heart disease (CHD) have led to dramatic improvements in survival for individuals with CHD. While adults with CHD represent a small percentage of admissions to the intensive care unit (ICU), the critical care needs of this population will grow as this population ages and develops increasingly complex cardiac and noncardiac conditions. Adults with CHD require special care in the ICU because of both their unique cardiovascular conditions and the multi-organ dysfunction that often accompanies their cardiac pathophysiology. This review aims to summarize the current epidemiology of critical care for adults with CHD, describe key …

Assessment Of Genes And Mirnas Expression In Alzheimer's Disease Samples Using Single And/Or Multiplex Preferential Amplification Pcr, Samanda F. Hickman

Theses (2016-Present)

Gene expression is measurable at the RNA and protein levels. It is a process by which genes produce functional products that are either non-coding RNAs or proteins. The non-coding RNAs or proteins of gene expression ultimately affect phenotype. Non-coding RNA (or mRNA) expression is measured by Northern blot or real-time quantitative PCR (RT-qPCR), while Western blot measures protein expression. Both require software to differentiate between the amounts of end products. Statistical analysis is employed to validate any differences among the measured values and to infer a correlation between the end products of various samples. There are several neurodegenerative diseases, including …

Analyzing Apoe Genotypic Variants And Expression Of Associated Genes And Mirnas In Alzheimer's Disease, Angelica Mendez

Theses (2016-Present)

One of the neurodegenerative diseases that affect the human brain is Alzheimer's disease (AD). It progressively destroys memory, thinking skills, and other critical mental functions of the brain. It is the most common cause of dementia due to the loss of cognitive functions. However, it differs from dementia, which includes other diseases resulting in cognitive deterioration and causing a person to lose independence and functionality. The apolipoprotein E (APOE) gene influences Alzheimer's risk. APOE protein transports cholesterol and other types of fat in the bloodstream. When the process fails, it contributes to the development of AD. Three genotypes of APOE …

Lac-Phe Induces Hypophagia By Inhibiting Agrp Neurons In Mice, Hailan Liu, Veronica L Li, Qingzhuo Liu, Yao Liu, Cunjin Su, Hueyxian Wong, Na Yin, Hesong Liu, Xing Fang, Kristine M Mcdermott, Hueyzhong Wong, Meng Yu, Longlong Tu, Jonathan C Bean, Yongxiang Li, Mengjie Wang, Yue Deng, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Junying Han, Megan E Burt, Sanika V Jossy, Chunmei Wang, Yongjie Yang, Benjamin R Arenkiel, Dong Kong, Yang He, Jonathan Z Long, Yong Xu

Faculty, Staff and Students Publications

Lactate-derived N-lactoyl-phenylalanine (Lac-Phe) was recently identified as an lactate-derived circulating metabolite that reduces feeding and obesity, but mechanisms that underlie the metabolic benefits of Lac-Phe remain unknown. Here we demonstrated that Lac-Phe directly inhibits hypothalamic neurons that express Agouti-related protein (AgRP), resulting in an indirect activation of anorexigenic neurons in the paraventricular nucleus of the hypothalamus (PVH). We also found that both AgRP inhibition and PVH activation are required to mediate Lac-Phe-induced hypophagia. Further, we show that Lac-Phe inhibits AgRP neurons via activating the ATP-sensitive potassium (KATP) channel, and inhibition of the KATP channel blunts effects of Lac-Phe to suppress …

High Prevalence Of Abnormal Baseline Lung Function In Pediatric And Young Adult Hematopoietic Stem Cell Transplant Recipients: A Report From The Transpire Study, Jane Koo, Richard Cooper, Stephanie L Edwards, Adam Lane, Sara Katherine Loveless, Lauren Strecker, Kelly E Lake, Kasiani C Myers, Christopher Towe, Jessica Patti, Laura L Walkup, Kathryn A Wikenheiser-Brokamp, Margaret L Macmillan, Philip Lacher, Tamara Griffin, Merve Tekman, Gabriel Salinas Cisneros, Kevin Wu, Matthew S Zinter, Fernando A Urrego, K Scott Baker, Matthew F Abts, Sheri Ballard, Jason L Freedman, Alexander Caraballo, Lisa R Young, Maureen B Josephson, Julian L Allen, Devaney M Camburn, Erin E Doherty, Mashid Sababi Azamian, Martha Arredondo, Manuel Silva-Carmona, Leslie E Lehmann, Wai Wong, Jonathan M Gaffin, William Mcalpine, Mona Li, Samuel B Goldfarb, Jason C Woods, Stella M Davies

Faculty, Staff and Students Publications

Background: Pulmonary complications are a major cause of morbidity and mortality in pediatric and young adult hematopoietic stem cell transplant (HSCT) recipients. The impact of preexisting lung dysfunction on posttransplant outcomes remains understudied.

Methods: In a multi-institutional prospective cohort of 444 patients (≤24 years) undergoing allogeneic HSCT at eight centers, baseline lung function was categorized as normal or abnormal using clinical history, imaging, pulmonary function tests (PFTs), and pulmonologist review. Spirometry and diffusion capacity were assessed at baseline, Day 100, 1 year, and 2 years post-HSCT.

Results: Baseline pulmonary dysfunction was present in 224 patients (50.4%), including impaired spirometry (46.4%), …

Rev-Erbα Regulates Brain Nad+ Levels And Tauopathy Via An Nfil3-Cd38 Axis, Jiyeon Lee, Ryeonghwa Kang, Sohui Park, Ibrahim O Saliu, Minsoo Son, Jaymie R Voorhees, Julie M Dimitry, Elsa I Quillin, Brian V Lananna, Young-Ah Goo, Guoyan Zhao, Erik S Musiek, Et Al.

2020-Current year OA Pubs

Nicotinamide adenine dinucleotide (NAD

A Randomised Controlled Trial Of Verbal Guidance Versus Verbal Guidance Supplemented By A Photographic Aid For Bystander Identification Of Intramuscular Tranexamic Acid Injection Sites In A Simulated Road Injury Scenario, Tim Nutbeam, Emily Foote, Lauren R. Rodgers, Jessica Thomas-Mourne, Rob Fenwick

Peninsula Medical School

Background: Non-compressible haemorrhage is a leading cause of preventable death following road injury. Tranexamic acid (TXA), when administered early, improves survival. Intramuscular (IM) administration offers a feasible route for early administration by lay bystanders. However, the ability of bystanders to correctly identify safe IM injection sites remains unclear. This study aimed to evaluate whether verbal guidance supplemented by a photographic aid improves the accuracy of site identification in a simulated road injury scenario. Methods: In this randomised controlled trial, 64 lay participants were recruited on a university campus and randomised to receive either (1) verbal guidance alone or (2) verbal …

Machine Learning For Dissolved Oxygen Prediction In The Manawatu River Catchment, New Zealand, Imokhai T. Tenebe, Eunice O. Babatunde, Nkpa M. Ogarekpe, Egbe Etu Etu, Joshua Emakhu, Kindness E. Etu, Obiora B. Ezeudu, Oluwarotimi S. Oladele

Faculty Research, Scholarly, and Creative Activity

Uncontrolled anthropogenic activities have increased river pollution, resulting in poor water quality and a growing need for continuous monitoring, which is time-consuming and costly. This study evaluated the accuracy of machine learning (ML) models in predicting dissolved oxygen (DO) levels, aiming to reduce field monitoring efforts and minimize the number of measured parameters. Regression models (Huber, Linear, Ridge), Bagging methods (Extra Trees, Random Forest, Decision Trees), and Boosting techniques (Gradient Boosting, Light Gradient Boosting, AdaBoost) were tested using data from three sites in the Manawatu Catchment, New Zealand. Data spanning 1989–2014 included 12 water quality variables and was split into …

Chimeric Antigen Receptor Natural Killer (Car-Nk) Cells: From Preclinical Promise To Clinical Reality In Cancer Immunotherapy, Hunter Cassidy Cochran, Kevin Ashkan Ghobadi, Armin Ghobadi

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR-NK cells offer the potential for "off-the-shelf" treatments with a favorable safety profile, due in part to their innate capacity for HLA-unrestricted tumor targeting and an absence of graft-versus-host disease. Landmark clinical studies using cord blood - derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the …

Plasma Proteome Correlations With Liver Stiffness In Pediatric Cholestasis Implicate Epithelial To Mesenchymal Transition, Benjamin L Shneider, Rupa S Kanchi, Sandra L Grimm, Sridevi Devaraj, Juliet Emamaullee, Jeremy Schraw, Philip J Lupo, Jorge A Bezerra, Kathleen M Loomes, John C Magee, Ronald J Sokol, Kasper S Wang, Alyssa Kriegmeier, Evelyn Hsu, Jean P Molleston, Philip Rosenthal, Rohit Kohli, Saul J Karpen, Simon P Horslen, M Kyle Jensen, Arianna Barbetta, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Pediatric cholestatic liver diseases can be characterized by rapidly progressive fibrosis. A multicenter cross-sectional analysis of vibration-controlled elastography in biliary atresia (BA), alpha-1 antitrypsin deficiency (A1AT), and Alagille syndrome (ALGS) was leveraged to interrogate the plasma proteome relative to liver stiffness measurements (LSM).

Methods: Slow off-rate modified aptamer scanning profiling of >7000 proteins in plasma from 187 children with BA (n=93), A1AT (n=31), ALGS (n=46), and healthy pediatric controls (n=17) was performed, and correlations with LSM were undertaken.

Results: There was an abundance of LSM correlated proteins (BA n=2720, A1AT n=694, ALGS n=5968). Interestingly, a distinct plasma proteome was …

Effects Of The Kcnq (Kv7) Channel Opener Ezogabine On Resting-State Functional Connectivity Of Striatal Brain Reward Regions, Depression, And Anhedonia In Major Depressive Disorder: Results From A Randomized Controlled Trial, Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough

Faculty, Staff and Students Publications

Background: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.

Methods: A double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n …

Hyaluronidase-1 Mediates Postprandial Suppression Of Hepatic Gluconeogenesis, Xi Chen, Sophie Dogné, Yanru Deng, Huiqiao Li, Jieyi Meng, Charlise Giang, Jan-Bernd Funcke, Leon G Straub, Michelle Dias, Sundararajah Thevananther, Qiang Tong, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Yu'e Liu, Nagireddy Putluri, Xia Gao, Miao-Hsueh Chen, Dongyin Guan, Hari Krishna Yalamanchili, Shangang Zhao, Nathalie Caron, Yi Zhu

Faculty, Staff and Students Publications

Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly suppressed to allow for glucose storage as glycogen and lipids in the liver. Failure to suppress gluconeogenesis after meals leads to elevated postprandial glucose levels, a key feature of type 2 diabetes. This dynamic switch is regulated by insulin and glucagon, but insulin resistance impairs this regulation. In this study, we identified a novel mechanism involving postprandial circulating hyaluronan (HA) and lysosomal hyaluronidase-1 (HYAL1) that suppresses hepatic gluconeogenesis by rewiring …

Adeno-Associated Virus-Mediated Silencing Of Sox4 Leads To Long-Term Amelioration Of Liver Phenotypes In Mouse Models Of Alagille Syndrome, Duncan Fox, Jun Xie, Jennifer L Burwinkel, Josh M Adams, Kashish Chetal, Marzieh Keivandarian, Yaniv Faingelernt, Sanjay Subramanian, Mario F Lopez, Anna L Peters, Nathan Salomonis, Neda Zarrin-Khameh, Guangping Gao, Stacey S Huppert, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Background & aims: In patients with Alagille syndrome (ALGS), bile duct paucity often leads to severe cholestatic phenotypes for which liver transplantation remains the only definitive treatment. No Food and Drug Administration-approved mechanism-based strategies exist to enhance biliary development in ALGS or other diseases with bile duct paucity. We aimed to identify a therapeutic target to address this unmet need.

Methods: Preclinical ALGS mouse models lacking 1 copy of Jag1 with or without conditional deletion of 1 or both copies of Sox9 were used. Sox4 levels were reduced genetically or with adeno-associated virus 8 (AAV8) vectors driving a Sox4-silencing sequence. …