Digital Commons Network^™

Hyperglycemia In Combination With Excess Fat Intake Promotes Renal Pyroptosis And Fibrosis Through Gα12-Dependent Endoplasmic Reticulum Stress, Muhammad Sohaib Khan, Boram Kim, Yerim Jeon, Jihoon Tak, Yun Seok Kim, Sang Gil Lee, Eun Byul Lee, Chang-Hoon Lee, Cheol Bin Eom, Hyun Sook Lee, Hyeon-Ki Jang, Nakyeom Lee, Jeong Hae Kie, Jee Myung Yang, Yoon Mee Yang, Sang Geon Kim

Faculty, Staff and Student Publications

Background: Chronic exposure to free fatty acids (FFAs) and glucose may disrupt metabolic homeostasis and initiate pathological processes. This study investigated the effects of hyperglycemia and fat overload on renal endoplasmic reticulum (ER) stress, pyroptosis and fibrogenesis in mice and the underlying basis. We hypothesized that the combined insult would more severely induce Gα12-dependent ER stress and renal complications.

Methods: Mice were subjected to either high fat diet (HFD)+streptozotocin (STZ), or STZ treatment, and AZ2 was used as an anti-diabetic agent. Blood sera were used for blood biochemistry, and tissues were employed for RNA sequencing, immunoblottings, TEM, histology and immunohistochemistry. …

Congenital Syphilis: From Near-Elimination To Crisis, Chad J Abresch, Irene A Stafford, Regan M Johnson, Kayode Olabanji, Ashleigh M Sutphen, Helen E Cejtin, Ashley Hoover

Faculty, Staff and Student Publications

This analytic essay examines the transformation of congenital syphilis (CS) in the United States from near-elimination to crisis. Drawing from the January 2025 Congenital Syphilis Summit in Atlanta, Georgia-convening public health leaders, Tribal health departments, the National Coalition of STD Directors, and Centers for Disease Control and Prevention experts-we contrast prevention systems during near-elimination (1998-2005) with the current crisis (2018-2025). Evidence revealed how dismantling public health infrastructure produced dramatically different outcomes, with CS cases increasing 937% over the past decade and racial/ethnic disparities worsening. American Indian/Alaska Native communities face rates up to 100 times higher than White populations in some …

Seeing Anxiety: Ecological Video Ethnography And Simulation To Understand Anxiety And Decision-Making In Dental Care, Mona Nasser, Hannah Drayson, Sally Hanks, Nicholas Peres, Michael Punt

Peninsula Dental School

BACKGROUND: Dental anxiety is a widespread barrier to care, often contributing to appointment avoidance, treatment disruption, and emotional strain for both patients and clinicians. While extensively studied as a psychological trait, less attention has been paid to how anxiety manifests situationally and relationally, through non-verbal, affective, and spatial cues within clinical encounters. Moreover, in certain contexts, such affective signals can intersect with decision-making processes, shaping how patients interpret, engage with, or withdraw from clinical choices.

OBJECTIVE: To explore how anxiety manifests within the micro-choreography of dental encounters, develop a taxonomy of 'anxious tells', and assess the utility of ecological video …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Exploring The Acceptability Of Integrating Dietitians Into Primary Care Dental Services For Children, Lauren Hallewell, Raul Bescos, Zoe Brookes, Tracey Parkin, Robert Witton, Patricia Casas-Agustench

School of Health Professions

BACKGROUND: Dental caries is a common childhood non-communicable disease strongly associated with high sugar intake. Beyond oral health, a poor diet can affect children's growth, development, and overall well-being. While dietary advice is central to preventive dental care, some primary care dental clinics have introduced body mass index (BMI) assessments and further dietary advice to address wider nutritional concerns in children. However, these efforts are often constrained by limited nutrition training, time constraints and concerns about sensitivity. Integrating dietitians into primary dental care may help overcome these barriers by enhancing dietary guidance, supporting broader nutritional needs and facilitating structured BMI …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Advancing Models Of Ptsd-Aud Comorbidity: Protocol For A Multimethod Framework Using Genetics And Ecological Momentary Assessment, Elizabeth A. Stinson, Samhita Lellapalli, Sage E. Hawn, Natalie Merrill, Lance M. Rappaport, Christina M. Sheerin, Vasiliki Michopoulos, Silviu-Alin Bacanu, Roseann E. Peterson, Abigail Powers, Ananda B. Amstadter

Psychology Faculty Publications

Background: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), which are moderately heritable, frequently co-occur and contribute to significant public health burdens, particularly among economically disadvantaged urban communities. There are noted sex differences in PTSD and AUD outcomes, with evidence suggesting women have heightened susceptibility to stress-related alcohol use. Preliminary PTSD-AUD ecological momentary assessment (EMA) findings support bidirectional associations across clinical outcomes. However, no studies to date have used PTSD-AUD comorbidity models as organizing frameworks to examine the temporal ordering and stability of within-person symptom dynamics underlying the maintenance or exacerbation of PTSD and AUD symptoms, including bidirectional and …

Sex And Gender Differences Between Experiences Of Discrimination And Physical Health: A Systematic Review, Saam Honarvar, Maryam Ajose, Bronwyn Sutherland, Alejandra Fernandez, Shakia T Hardy, Miguel Ángel Cano, Samaah Sullivan

Library Staff Publications

Background: Despite a plethora of previous research on experiences of discrimination and physical health outcomes, there has been less attention to sex/gender differences, although some research suggests a greater stress-related biological and behavioral impact on women.

Methods: Five databases were reviewed up to May 2023 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included studies that examined self-reported experiences of discrimination and physical health outcomes among adults (aged 18+) in the United States if results were either stratified by sex/gender or tested a sex/gender-by-discrimination interaction term.

Results: A total of 3,397 articles were extracted, and 50 …

Microplastics, Nanoplastics And Liver Disease: An Emerging Health Concern?, Shilpa Chokshi, Ashwin Dhanda, Matthew E. Cramp, Richard Thompson

Peninsula Medical School

Human liver tissue has been found to contain microplastics and nanoplastics (MNPs), with evidence that hepatic MNP accumulation has markedly increased over the past 10 years, prompting critical questions regarding their potential causal role in liver disease. In cell-based and murine models, MNP exposure can trigger oxidative stress, fibrogenesis and inflammation, pathological features that resemble those of advanced liver disease, suggesting shared mechanistic pathways. Furthermore, the capacity for MNPs to act as vectors for microbial pathogens, antimicrobial resistance, endocrine-disrupting chemicals and carcinogenic additives might have important implications for liver pathology. This Perspective examines emerging evidence on the consequences of MNPs …

An Insidious Interstice: Understanding Cognition And Language Behaviour Through The Eyes Of Juvenile Justice Professionals, Anne M. Perrotti, Allison T. Chappell, Tancy Vandecar-Burdin

Human Movement Studies & Special Education Faculty Publications

Introduction

Despite evidence suggesting language and cognition deficits are prevalent for justice involved youth, little research explores how juvenile justice personnel experience language and cognition behaviours in the youth they serve.

Aims

This qualitative study explored how juvenile justice personnel understand language and cognition skills and deficits in justice involved youth.

Methods

Twenty-two U.S. juvenile justice professionals participated in individual, semi-structured interviews. Questions focused on individual understanding of receptive language, expressive language, social communication, and cognition (i.e., problem-solving, predicting consequences and impulsiveness) in juveniles served. Using a phenomenological lens, transcripts were coded identifying themes and sub-themes of participant responses.

Results …

Organ Chips And Translational Research: Identifying And Examining New Ethical Issues, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Organ chips, also known as organ-on-a-chip devices, tissue chips, or microphysiological systems, have emerged over the last decade as a promising translational technology amidst growing concern about the translational crisis between laboratory research and patient bedside. Pointing to high rates of failure between nonhuman animal models and safety and efficacy in humans, organ chips and similar new approach methods have attracted substantial public and private investment. As human-cell-based alternatives to animal models, organ chips promise more predictive, efficient, and ethical platforms for pharmaceutical and toxicity testing. Engineered cultivation systems that enable cells to assemble into tissue-like structures (e.g. kidney, brain, …

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Access To Digital Health Technologies: Personalized Framework And Global Perspectives, Sanjiv M Narayan, Mina K Chung, Demilade Adedinsewo, Luisa C C Brant, Leslie L Davis, David Duncker, Jennifer L Hall, Janet K Han, Carolyn S P Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A Armoundas

Center for Medical Ethics and Health Policy Staff Publications

The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …

Pd-L1-Centric Whole Blood-Based Immune Signature Profiles Of Tuberculosis Patients During Therapy, Johanna Eggeling, Martina Sester, Christoph Lange, Jan Heyckendorf, Barbara Kalsdorf, Anna M Mandalakas, Andrew R Dinardo, David Lewinsohn, Dagmar Schaub, Tina Schmidt, Eva Tolosa, Maja Reimann, Patricia M Sánchez Carballo

Faculty, Staff and Students Publications

This prospective study investigated whole blood-based immune cell biomarkers for pulmonary tuberculosis (TB) immunoprofiling. Blood samples from 34 healthy controls and 51 tuberculosis patients were analyzed at three timepoints: Prior to therapy (T0), after 14 days of therapy (T1), and at the end of treatment (Te). Using multiparameter flow cytometry, 386 immune cell populations were analyzed. Predictive models were developed using two machine learning algorithms. A TB5LF change score, which was based on five cell populations, effectively distinguished tuberculosis patients from controls (AUC = 0.89) and tuberculosis patients before and at the end of treatment (AUC = 0.92). Similarly, the …

Astrocytic Sox9 Overexpression In Alzheimer’S Disease Mouse Models Promotes Aβ Plaque Phagocytosis And Preserves Cognitive Function, Dong-Joo Choi, Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debosmita Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R Williamson, Teng-Wei Huang, Kaitlyn Sanchez, Joanna Jankowsky, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes …

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

Case Report: Primed Dendritic Cell Immunotherapy For Multiple Solid Tumors, Jeffrey Jones, Aly Alrabaa, William Decker, Luis Ferbeyre, Gregorio Viramontes, Rafael Gonzalez, Elideth Angulo, Antonio Zamudio, Raul Hernandez, Stephen Noga, Susana Hernandez-Reyes, Paul Zhang, Darryl Smith, Ara Karamanian, Luis Tamara, Dalton Greenwood, Matthew Halpert

Faculty, Staff and Students Publications

Many patients with advanced solid tumors ultimately develop resistance to conventional therapies, with especially limited options for those experiencing rapid progression or poor performance status, highlighting the need for personalized immunotherapies capable of inducing durable responses. In this retrospective case series, we describe the clinical course and outcomes of five adults (4 male, 1 female; median age 51 years [range, 39-62]) with metastatic solid tumors who achieved complete and durable remission following doubly loaded autologous dendritic cell therapy after failure of standard treatments, such as immune checkpoint inhibition, radiation, surgery, or endocrine therapy. Five patients, including prostate adenocarcinoma (n=1), malignant …

Case Series Of Nizon-Isidor Syndrome By Heterozygous Variants In Med12l With Further Evidence Of Mitotic Instability In One Case With Diploid-Triploid Mosaicism, Russell Stewart, Kimberly M Ezell, Deanna S Bell, Brian Corner, Ashley Mcminn, Joy D Cogan, Rizwan Hamid, Lynette Rives, John A Phillips, Nina Paddu, Gitanjali Srivastava, Ronit Marom, Farah A Ladha, Claudia Soler-Alfonso, Rachel Franciskovich, Mary Koziura, Sumit Pruthi, Gabriele Richard, Christina B Sheedy, Undiagnosed Diseases Network, Thomas Cassini

Faculty, Staff and Students Publications

Nizon-Isidor syndrome is a rare disorder caused by heterozygous variants in MED12L, with only eight documented cases in the literature. Here, we present three additional cases of this syndrome. Proband 1 was a 7-year-old female who presented with developmental delay, right-leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a MED12L variant, NM_053002.5:c.3559+2T>G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of MED12L exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing …

Using Medication Pass Analysis To Examine Longitudinal Changes In Va Inpatient Nurse Staffing And Workload Before And Through The Covid-19 Pandemic: 2019-2022, Melissa K Knox, Chase S Eck, Lynette Dorsey, Paras D Mehta, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic resulted in extended disruption to the health care system. National-level data-driven comparisons of inpatient nurse staffing and workload before and during the pandemic have been limited.

Objectives: Assess the extent to which registered nurse (RN) staffing and workload changed from prepandemic levels in a national integrated health care system.

Research design: Longitudinal descriptive analysis. Medication pass analysis using bar code medication administration data for the peak-time medication pass (PTM) assessing year-over-year changes from 2019 to 2022. To assess significance of year-over-year changes in means we used the Welch 2-sample t test.

Subjects: Staff (N=42,999) administering PTM …

Once-Weekly Navepegritide In Children With Achondroplasia: The Approach Randomized Clinical Trial, Ravi Savarirayan, Ciara Mcdonnell, Carlos A Bacino, Daniel G Hoernschemeyer, Janet M Legare, M Jennifer Abuzzahab, Paul L Hofman, Philippe M Campeau, Josep Maria De Bergua Domingo, Leanne M Ward, Kevin Smit, Alden Smith, Meng Mao, Michael S Ominsky, Lærke C Freiberg, Aimee D Shu, Hanne B Hove

Faculty, Staff and Students Publications

Importance: Historically considered a skeletal dysplasia characterized by disproportionate short stature, achondroplasia is a condition with multisystemic effects due to the widespread expression of the fibroblast growth factor receptor 3 variant throughout the body, impacting muscle, neurological function, cardiorespiratory health, and health-related quality of life.

Objective: To evaluate the efficacy, safety, and tolerability of once-weekly navepegritide, an investigational prodrug of C-type natriuretic peptide, while assessing benefits beyond growth that may have important implications for complications and health-related quality of life in children with achondroplasia.

Design, setting, and participants: Enrollment for this pivotal phase 2b, randomized, double-blind, placebo-controlled trial (APPROACH) was …

Prevalence Of Substance Use In Northwest Syria: A Cross-Sectional Study, Isabel Draper, Dania Albaba, Heba Mesbah, Huda Taktak, Nidhal Saadoun, Mohammad Alhusein, Elharit Alissa, Anas Barbour, Zaher Sahloul, Nidal Moukaddam

Faculty, Staff and Students Publications

Objectives: Syria has undergone significant socio-political turmoil since 2011 as internal conflict displaced portions of the population, destroyed infrastructure, and destabilized the economy. In the context of multilevel healthcare system disruptions, there have been increasing reports of substance use. This study seeks to evaluate patterns of substance use in Northwestern Syria.

Methods: Trained staff administered questionnaires to community members in Azaz, Syria. Questions focused on the substance use prevalence, societal and public health impacts, and perspectives on treatment availability.

Results: 480 individuals were surveyed (80·88% male, 19·12 % female; 43·39% were 18-25 yrs, 11·5% reported personal substance use). H-booz (amphetamines), …

Surface Marker Identification To Capture Live Circulating Tumor Cells In Metastatic Triple-Negative Breast Cancer, Bree M Lege, Khushali J Patel, Brendan Panici, Ping Gong, Michael T Lewis, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies. Circulating tumor cells (CTC) are invaluable for monitoring metastatic tumor progression and treatment response but are difficult to capture because of their rarity and heterogeneity. Surface-based staining for live CTCs is essential to preserve RNA quality in single cells, but current markers tend to perform poorly on more mesenchymal tumor cells such as TNBCs. To enhance live TNBC CTC detection, we developed a workflow for live CTC capture and single-cell RNA sequencing (scRNA-seq). Using a mouse model of metastatic TNBC, we identified four new CTC surface markers, AHNAK2, …

Lysine Demethylase 4a Is A Centrosome-Associated Protein Required For Centrosome Integrity And Genomic Stability, Pratim Chowdhury, Xiaoli Wang, Richard I Han, Manga Motrapu, Ashley G Boice, Yuya Nakatani, Sofia Vargas-Hernandez, Julia F Love, Claude Chew, Sandra L Grimm, Dereck Mezquita, Frank M Mason, Elisabeth D Martinez, Cristian Coarfa, Cheryl L Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution. We additionally uncovered that KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis and integrity; a previously unknown functionality unlinked to altered expression of genes regulating centrosome number. We find that KDM4A interacts with …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …

Epithelial-Mesenchymal Transition And Stress Adaptations Underlie Yttrium-90 Resistance In Liver Cancer Cell Lines, Alexander Zheleznyak, Dhanusha Duraiyan, Prasanth Thunuguntla, Jessica Camacho, Shuang Wu, Jingxia Liu, Jason D Weber, Daniel L J Thorek, Benjamin S Strnad, Ryan C Fields, Matthew A Ciorba, Christine Yoon, Valerie Blanc, Nicholas Davidson, Jessica Silva-Fisher, Christopher D Malone

2020-Current year OA Pubs

UNLABELLED: Molecular signatures predict prognosis in hepatocellular carcinoma, but their relevance to transarterial radioembolization (TARE) with yttrium-90 (90Y) is unknown. We aimed to identify baseline and treatment-induced pathways associated with response and nominate biomarkers. Ten transcriptomically diverse human liver cancer cell lines were exposed to escalating activities of glass 90Y microspheres for 10 days. Normalized AUC values quantified sensitivity. Whole-transcriptome RNA sequencing at baseline and after treatment was analyzed with elastic net regression and gene set enrichment. Findings were corroborated by qRT-qPCR and exploratory analysis of pretreatment tumor samples from patients undergoing TARE. Liver cancer cell line responses to 90Y …

The Impact Of Pasifikas In Medicine On Pacific Islander Medical Student Experiences, Devon Hori Harvey, Micah Ngatuvai, Siale Vaitohi, Paige E. Faasuamalie, Maegan Tupinio, Lisa H. Smith

Student Papers, Posters & Projects

BACKGROUND: Pacific Islanders experience significant health disparities. One contributing aspect to these disparities is the lack of racial concordance as Pacific Islanders are underrepresented in the U.S. physician work force. Several factors contribute to this underrepresentation including lack of support systems for Pacific Islander premed and medical students. Pasifikas in Medicine (PiM) is a recently established national student organization founded to provide support for Pacific Islander premed students, medical students, residents, fellows and attending physicians. This study seeks to understand the impact of PiM on medical student experiences.

METHODS: An anonymous survey was distributed to the PiM listserv and to …

Co-Developing Strategies For Leprosy Management In Malaysia: A Transdisciplinary Research Approach Involving Individuals Affected By Leprosy And Other Stakeholders, Norana Abdul Rahman, Vaikunthan Rajaratnam, Ruth Mh Peters, Marjolein Bm Zweekhorst, Pamela Wright Phd, Ms, Med, Rn, Cen, Karen Morgan, Mohamed Rusli Abdullah

Publications

Despite Malaysia's low leprosy prevalence, new cases continue to emerge in rural and Indigenous communities. National strategies often prioritise elimination and surveillance, while overlooking the needs and challenges of individuals affected by leprosy and those managing their care. This study employed a transdisciplinary research approach, guided by the Dialogue Model, to co-develop context-specific strategies to improve the lives of those affected through participatory engagement with both groups. Conducted across three high-burden states in Peninsular Malaysia, the research involved a desk review and stakeholder mapping, followed by 40 in-depth interviews with affected individuals and other stakeholders. These were complemented by a …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …