Digital Commons Network^™

Malt1 Protease Inhibition Restrains Glioblastoma Progression By Reversing Tumor-Associated Macrophage-Dependent Immunosuppression In Mice, Juliana Hofstätter Azambuja, Saigopalakrishna Yerneni, Lisa Maurer, Hannah Crentsil, Gabriela Debom, Linda Klei, Mei Smyers, Chaim Sneiderman, Kristina Schwab, Rajesh Acharya, Aivi Nguyen, Josie Emery, John Little, Jeffrey Meridew, Yijen Lin Wu, Prasanna Ekambaram, Dong Hu, Pete Gough, John Bertin, Ari Melnick, Gary Kohanbash, Riyue Bao, Peter Lucas, Linda Mcallister-Lucas

College of Life Sciences Faculty Papers

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. We show that MALT1 is expressed in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis in macrophages, leading to enhanced macrophage migration and polarization toward an immunosuppressive ('M2-like') phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage anti-tumor 'M1-like' phenotype. Preclinical in vivo analysis shows that MALT1 inhibitor treatment results in immuno-reactivity of GBM-associated macrophages …

A Distinct Form Of Fat Fibrosis Is Linked To Insulin Resistance In People With Hiv, Diana L Alba, Alaa Abdellatif, Moon Kyung Choi, Stephen M Brown Mayfield, Thuy An T Pham, David I Berrios, Antonio E Rodriguez, Marin Ewing, Tony R Figueroa, Judy Gonzalez-Vargas, Ningyan Zhang, Zhiqiang An, Dawei Bu, Steven G Deeks, Philipp E Scherer, Peter W Hunt, Suneil K Koliwad

The Brown Foundation: Institute of Molecular Medicine

BACKGROUND

Despite antiretroviral therapy (ART), people with HIV (PWH) are at heightened risk for insulin resistance (IR) and type 2 diabetes (T2D). Subcutaneous adipose tissue (SAT) fibrosis contributes to metabolic disease, but its role in IR among PWH is unknown. We investigated the relationship between SAT fibrosis and IR in PWH, along with transcriptional signatures to distinguish it from SAT fibrosis due to obesity.

METHODS

We analyzed body composition and SAT fibrosis (hydroxyproline) in 46 PWH and 74 people without HIV (PWoH), excluding individuals with T2D. We examined fibrosis-related gene transcription in the SAT using a targeted panel and measured …

Surgical Outcomes Of Hidradenitis Suppurativa Excision: Factors Impacting Wound Healing Time, Christina Huang, Scott H. Koeneman, Sherry Yang, Sami Tannour

Department of Surgery Faculty Papers

Hidradenitis suppurativa (HS) can be treated surgically to excise recurrent and recalcitrant regions of disease activity. However, surgical outcomes are highly variable depending on closure method, concomitant medical management and area of excision. In this study, we aim to characterise the healing courses from HS excision in a case series. To reduce operator variability, we opted to conduct a case series from a single surgeon. Surgeries conducted from June 2024-December 2025 by surgeon S.T. were included, and the postoperative course was followed until February 2026. Surgical details and postoperative course for 34 sites of HS across 20 patients were analysed. …

Long-Term Poverty, Rurality, And Geographic Disparities In Colorectal Cancer: A Spatial Analysis In Texas, Jooyeon Lee, Lorna Mcneill

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality in the United States and shows substantial geographic variation. Socioeconomically disadvantaged communities experience elevated CRC incidence, yet few studies have analyzed multi-decade poverty measures for long-term structural disadvantage.

Methods: We analyzed CRC incidence from 2017 to 2021 across Texas using Texas Cancer Registry data. Age-sex-race/ethnicity standardized cases were incorporated as offsets in Bayesian spatial models to generate tract-level posterior mean relative risks. We evaluated four tract-level poverty measures (high poverty in 2021; persistent poverty since 1990; enduring poverty since 1980 and 1970), Rural-Urban Commuting Area (RUCA) classifications, …

Development Of A Structurally Distinct Topbp1 Inhibitor That Enhances Parp Blockade And Reverses Osimertinib Resistance, Yang Xiao, Lidija A Wilhelms Garan, Helena Folly-Kossi, Weei-Chin Lin

Faculty, Staff and Students Publications

Therapeutic resistance remains a major challenge in cancer treatment, driven by compensatory signaling and stress response pathways that sustain tumor survival. Topoisomerase IIβ-binding protein 1 (TopBP1), a multifunctional scaffold protein with nine BRCT domains, integrates replication stress signaling with oncogenic networks and is frequently overexpressed in aggressive cancers. Its BRCT7/8 domains mediate critical interactions with E2F1, mutant p53, MIZ1, PLK1, and CIP2A, making TopBP1-BRCT7/8 an attractive therapeutic target. Using docking-guided screening and structure-activity relationship–driven optimization, we developed CS18 as a potent and selective BRCT7/8 inhibitor that disrupts oncogenic TopBP1 complexes without interfering with DNA replication. CS18 suppresses MYC transcriptional programs, …

Young-Onset Stroke In The Uae: A Single-Centre Retrospective Analysis Of Risk Factors And Outcomes, Sobia Siddiq, Saryia Adra, Kamel A. Samara, Batool Aldaher, Mohamad Emad Aldeen Mahfouz, Nour Sakan, Fathima Musfira, Roomiyah Riyaz Assadi, Ahlam Mohamed Almarzooqi, Hiba Jawdat Barqawi, Eman Abu-Gharbieh

Abington Jefferson Health Papers

BACKGROUND: Young-onset stroke represents a growing public health concern, yet data from the United Arab Emirates (UAE) remain limited. This study aimed to examine the risk factors and clinical outcomes associated with young-onset stroke in the UAE.

METHODS: A retrospective chart review was conducted on 419 patients aged below 50 years who were admitted at Al Qassimi Hospital, Sharjah, UAE, with a diagnosis of stroke between 2016 and 2022. Data on demographics, comorbidities, stroke subtype, management, and outcomes were collected and analyzed using Python-based statistical libraries.

RESULTS: The study population comprised predominantly of male individuals (78.28%), with most patients originating …

Shared Neural Geometries For Bilingual Semantic Representations In Human Hippocampal Neurons, Xinyuan Yan, Ana G Chavez, Melissa Franch, Kalman A Katlowitz, Ivy Gautam, Brian Kim, Aaditya Krishna, Aadit Shrivastava, Katie Van Arsdel, James Belanger, Assia Chericoni, Taha Ismail, Elizabeth A Mickiewicz, Danika Paulo, Hanlin Zhu, Alica M Goldman, Vaishnav Krishnan, Atul Maheshwari, Eleonora Bartoli, Nicole R Provenza, Seng Bum Michael Yoo, Benjamin Y Hayden, Sameer A Sheth

Duncan NRI Faculty and Staff Publications

The human brain has the remarkable ability to comprehend and express similar concepts in multiple languages. To understand how it does so, we examined responses of hippocampal neurons during passive listening, directed speaking, and spontaneous conversation in both English and Spanish in a small group of balanced bilinguals. We found a small number of putative "cross-language neurons," whose responses to equivalent words (e.g., "tierra" and "earth") are correlated. However, neurons' semantic tunings differed substantially by language, suggesting language-specific neural implementations. Instead, the crucial driver of translation was a preserved geometric organization of neural responses between the two languages, one that …

Dose-Expansion Study Of Obi-999, A Globo H-Targeting Antibody-Drug Conjugate, In Patients With Advanced Solid Tumors, Apostolia Maria Tsimberidou, Darren Sigal, Anna Varghese, Daniel Vaena, Li-Yuan Bai, Ming-Huang Chen, Chun-Nan Yeh, Chia-Jui Yen, Mehmet A Baysal, Abhijit Chakraborty, Ingly Lee, Chi-Sheng Shia, Konul Ristoski, Dong Xu

Children’s Nutrition Research Center Staff Publications

Background: OBI-999 is an antibody-drug conjugate consisting of the Globo H-targeting antibody OBI-888 linked to the cytotoxic payload monomethyl auristatin E. In a dose-escalation study, the OBI-999 recommended phase 2 dose (RP2D) was 1.2 mg/kg every 3 weeks. This dose-expansion study evaluated the efficacy and safety of OBI-999 in patients with pancreatic cancer, colorectal cancer (CRC), or other tumor types ("basket cohort") and tumoral Globo H H-scores ≥100 (NCT04084366).

Patients and methods: Patients were treated at RP2D of OBI-999. We assessed response, progression-free survival (PFS), treatment-emergent adverse events (TEAEs), and pharmacokinetics of OBI-999.

Results: Of 29 patients treated, …

Endometrial Cells With High Aldh Activity Contribute To Uterine Development And Regeneration, Sydney E Parks, Genesis J Herrera, Ting Geng, Linda Alpuing Radilla, Brooke A Thigpen, Xiaoming Guan, Diana Monsivais

Faculty, Staff and Students Publications

Adult stem cells are thought to drive the regenerative potential of the endometrium and contribute to the pathogenesis of endometriosis; however, their identity and defining features remain to be characterized. Here, we used in vivo and in vitro approaches to demonstrate that cells with high aldehyde dehydrogenase 1 activity (ALDHHI cells) were long-lived progenitors in the endometrium with a higher organoid formation capacity, long-term passaging potential, and stemness gene signatures. Using lineage tracing with an Aldh1a1creERT2/+; Rosa26LSL-tdTomato reporter mouse, Aldh1a1+ epithelial cells expanded during postnatal development, Aldh1a1+ stromal cells expanded during estrous cycling, and both populations of Aldh1a1 …

An Online Epilepsy Self-Management Tool For Patients With Epilepsy: A Formative Usability Study, Youngran Kim, Kimberly Martin, David M Labiner

Faculty, Staff and Student Publications

Background: Epilepsy is a serious chronic neurological condition with no permanent cure. Continual self-management is important to mitigate seizure frequency and optimize quality of life in people with epilepsy who have greater disparities in accessing epilepsy care. The Management Information & Decision Support Epilepsy Tool (MINDSET [UTHealth, University of Arizona, and Radiant Digital]) was developed to enhance accessibility to epilepsy self-management (ESM) assessment and treatment. The purpose of this formative usability pilot study was to assess the user experience and functionality of MINDSET 2.0, an enhanced cross-platform online version of MINDSET, among a sample of patients with epilepsy prior to …

Protocadherin 9 Promotes Cell Survival Of Different Bipolar Cell Types In The Developing Mouse Retina, Collin Todora, Cesiah C Gomez, Elizabeth Zuniga-Sanchez

Faculty, Staff and Students Publications

Neural circuit assembly relies on different neuronal types coming together to form a functional circuit. The question of how the appropriate number of each type is integrated into an emerging circuit remains relatively unknown. To answer this question, we used the mouse retina to uncover the molecular mechanisms responsible for neuron-type integration in a developing circuit. In the mammalian retina, bipolar cells (BCs) are a class of interneurons that relay visual information from photoreceptors to ganglion cells. Extensive studies have shown there are 15 distinct BC types: 6 types of OFF cone bipolars, 8 types of ON cone bipolars, and …

Childhood Cancer Predisposition Study: A Prospective Registry And Biorepository Protocol, Jennie Vagher, Junne Kamihara, Surya Rednam, Philip J Lupo, Garrett M Brodeur, Joshua Schiffman, Lisa Diller, Lauren Desrosiers-Battu, Sharon E Plon, Kim E Nichols, Samuel L Volchenboum, David Malkin, Anita Villani, Christopher C Porter

Faculty, Staff and Students Publications

Introduction: Cancer is the most common cause of disease-related mortality in children, highlighting the urgent need for improved care in this population. It is estimated that >15% of children diagnosed with cancer harbour a germline pathogenic variant in a cancer predisposition gene which confers an increased risk to develop cancer. There are over 100 genes associated with cancer predisposition syndromes (CPSs) and greater availability and acceptability of genetic testing in the last decade has facilitated their recognition in childhood. However, individually, each of these CPSs is rare, impeding robust research and advancement of clinical care. Once a specific CPS is …

Larotrectinib In Trk Fusion Differentiated Thyroid Carcinoma: Updated Trial Data, Steven Waguespack, Marcia Brose, Jessica J Lin, Ray Mcdermott, Mohammed Almubarak, Jessica Bauman, Michela Casanova, Shivaani Kummar, Se-Hoon Lee, Damian Rieke, Do-Youn Oh, Changsong Qi, Natascha Neu, Domnita-Ileana Burcoveanu, Chiara Mussi, Alexander Drilon, David Hong, Maria Cabanillas

Department of Medical Oncology Faculty Papers

Larotrectinib is a first-in-class, highly selective, central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for tumour-agnostic use in TRK fusion cancer. It has previously demonstrated rapid and durable disease control and favourable safety in patients with advanced TRK fusion thyroid carcinoma (TC). After an additional 4 years of follow-up with the inclusion of two additional patients, and utilising an independent review committee (IRC) to assess overall response rate (ORR), we report updated pooled analyses from three phase 1-2 larotrectinib clinical trials, focusing only on patients with TRK fusion differentiated TC (DTC). The primary endpoint was the IRC-determined ORR per …

Recognition Of Autism Characteristics In Females: An Examination Of Stakeholders, Laurel Lyn Bishop

Theses and Dissertations

Autism is a neurodevelopmental communication disorder, characterized by differences in social communication, attention, interests, and sensory perception. Diagnostic criteria have historically applied to males, but clinical diagnostic criteria beginning in 2022 now include slight differences in traits comprising the female phenotype. Until recently, autistic females may be missed by the professional and education community or diagnosed later than males. Like their autistic male counterparts, they face an increased risk of suicidal ideation, but they also face more difficulties in peer relationships, academic problems, and increased anxiety and depressive symptoms, but may not get supports. School-age girls spend their days with …

Sex-Aware Causal Inference Assessment Of The Immune System In Complex Neurodegenerative Diseases, Frida Lona-Durazo, Ross P Byrne, Marc-Olivier Pilon, Michael D Greicius, Marie-Pierre Dubé, Michael E Belloy, Russell L Mclaughlin, Sarah A Gagliano Taliun

2020-Current year OA Pubs

Sex differences, in terms of prevalence, symptoms and disease progression, are established in the aetiology of complex neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but the underlying biology driving these differences remains poorly understood. There is emerging evidence from genetic and functional analyses affirming the role of the immune system in such diseases, but a thorough assessment of sex differences in the link between the immune system and neurodegenerative diseases remains lacking. Here, we applied a robust causal inference approach, two-sample Mendelian randomization, to evaluate the causal effect of immune-related protein levels on three neurodegenerative diseases …

Stromal Cell Senescence Augments Haematopoietic Cell Fitness In Clonal Haematopoiesis., Jayna J Mistry, Kira Young, Anna Navarro Figueredo, Gibran Edun, Alicia G Aguilar-Navarro, Patricia A Colom Díaz, Maria Telpoukhovskaia, Inés Fernández Maestre, Sheng F Cai, Katharina S Götze, Anastasia N Tikhonova, Ross L Levine, Jennifer J. Trowbridge

Faculty Research 2026

Microenvironment remodelling impacts tumour growth and metastasis, but whether remodelling promotes pre-malignant clonal fitness remains unknown. Here, using single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH), we identify mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Elevated bone-marrow MSC senescence is also observed in humans with CH driven by several common somatic mutations. MSC senescence is induced by mutant haematopoietic cells in a contact-independent manner through production of soluble factors including TNF-α and IL-6. These cytokines activate a Stat3-driven pathway that is necessary and sufficient for MSC senescence induction. Genetic …

Impact Of Trisomy 21 On Post Pull-Through Enterocolitis And Bowel Function In Children With Hirschsprung Disease: A Pcplc Analysis., Marshall W. Wallace, Scott S. Short, Rachel C. Crady, Ron W. Reeder, Hira Ahmad, Kelly Austin, Andrea Badillo, Casey M. Calkins, Megan M. Durham, Julie R. Fuchs, Christopher Gayer, Julia E. Grabowski, Jamie C. Harris, Charles R. Hong, Ankur Rana, Rebecca M. Rentea, Nelson Rosen, Payam Saadai, Caitlin A. Smith, K Elizabeth Speck, Cristine S. Velazco, Richard J. Wood, Michael D. Rollins

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: We evaluated whether Trisomy 21 (T21) affected bowel management use, ability to toilet train for stool, and rates of Hirschsprung-Associated Enterocolitis (HAEC) in children with Hirschsprung disease (HD). We hypothesized that T21 would be associated with increased rates of HAEC, bowel management program (BMP) use, and delayed toilet training for stool.

METHODS: Children with HD in the Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) database who underwent primary pull-through were included and stratified by T21 status: HD only versus HD + T21. Children requiring a redo pull-through, initially managed with a stoma, or those who had inadequate follow-up were …

Sez6-Targeting Antibody-Drug Conjugate Abbv-706 In Advanced Small Cell Lung Cancer And Solid Tumors: A Phase 1 Trial, Lauren Averett Byers, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms. In an open label, phase 1 trial, ABBV-706, an antibody-drug conjugate with a SEZ6-directed antibody linked to topoisomerase-1 inhibitor (Top1i), was administered intravenously every 3 weeks (Q3W) to 288 patients with advanced solid tumors; 240 received monotherapy, including 124 with relapsed/refractory (R/R) SCLC. Primary objectives of dose escalation (part 1, advanced solid tumors), dose optimization and expansion (part 2, R/R SCLC only) and dose expansion (part 4, central nervous system tumors and high-grade neuroendocrine neoplasms only) were to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity …

Biological Aging And Generational Shifts In Early-Onset Cancer Risk, Ruiyi Tian, Xiaoyu Zong, Duo Ren, Stefani Tica, Daniel Hong, Oluseye Oduyale, Jason D Buenrostro, Ramaswamy Govindan, Yin Cao

2020-Current year OA Pubs

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase for those born 1965-1974 versus 1950-1954, and was associated with early-onset solid cancer risk (hazard ratio (HR)

Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull

2020-Current year OA Pubs

We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories …

Financial Toxicity And Cost-Related Imaging Nonadherence In Pediatric Outpatient Imaging, Shireen E Hayatghaibi, Gregory L Jordan, Tucker Hansen, Amy E Ensing, Aditi Gupta, Evan A Mihalakakos, Bin Zhang, Pradipta Debnath, Carrie C Coughlin

2020-Current year OA Pubs

RATIONALE AND OBJECTIVES: Financial toxicity, defined as the financial burden and stress experienced due to medical costs, is increasingly recognized as a key patient-reported outcome and has been linked to cost-related non-adherence in adult populations. However, its prevalence and impact in pediatric imaging are unknown. We examined the prevalence and predictors of financial toxicity among families of children undergoing outpatient imaging and its association with imaging non-adherence.

MATERIALS AND METHODS: We conducted a prospective cross-sectional survey of parental caregivers of children (< 18 years of age) undergoing outpatient imaging at two free standing children's hospitals in the U.S. (July 2024-May 2025). Financial toxicity was measured using the adapted FACIT-COST instrument and scores < 26 indicated high financial toxicity. Multivariable logistic regression examined associations between family characteristics and high financial toxicity.

RESULTS: Among 399 caregivers, the mean FACIT-COST score was 24.6 (SD 10.2), and 49% were categorized as having …

Language And Sound Exposure Across Neonatal Intensive Care Hospitalization And Relationships With Early Outcome, R Pineda, L J Woodward, Z A Vesoulis, C D Smyser, T E Inder, A M Mathur, B L Schlaggar

2020-Current year OA Pubs

OBJECTIVES: Examine relationships between quantitative measures of language and sound exposure in the NICU and infant neurobehavior.

STUDY DESIGN: Sixty-four preterm infants (≤28 weeks of gestation) had language and sound exposure measured across four time points: within two weeks of birth and at 30, 34, and 35-41 weeks postmenstrual age (PMA). Neurobehavior was assessed at 35-41 weeks PMA using the NICU Network Neurobehavioral Scales.

RESULTS: Higher average decibel levels in the NICU environment were associated with lower infant orientation scores (p = 0.04, β = -0.33). Higher peak decibel levels were associated with greater hypertonia (p = 0.01, β = …

Attrition Of The Midwifery Workforce: Understanding Factors Associated With Leaving The Profession, E. Brie Thumm, Amy H. Goh, Elizabeth G. Phillips, Zachary Giano

College of Health Professions Faculty Papers

OBJECTIVE: To understand why advanced practice midwives (certified nurse-midwives and certified midwives) leave the workforce.

STUDY SETTING AND DESIGN: A multi-method, multi-source investigation included secondary analysis of certification data of advanced practice midwives and a cross-sectional online survey with closed- and open-ended items. Advanced practice midwives' active certification data were used to compare self-reported demographic characteristics of advanced practice midwives who reported working in the discipline of midwifery to those who did not (n = 9704). A survey was conducted in 2022 with individuals who allowed their certification to lapse between 2017 and 2021 (n = 303) and individuals who …

Navigating Undone Science: The Search For Adequate Endometriosis Care, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Endometriosis is an estrogen-dependent disease in which tissue similar to the lining of the uterus grows elsewhere in the body leading to a variety of symptoms including heavy and prolonged menstruation, chronic pain, cysts, infertility, and gastrointestinal issues. Despite being one of the most common gynecologic conditions, much remains unknown about potential risk factors for endometriosis, its etiology, and treatment options. First and second-line biomedical treatment options, complementary and alternative medicine, and lifestyle changes are all treatment options that people living with endometriosis (PLE) leverage to manage their symptoms. This article draws on in-depth interviews with 52 people living with …

All-Cause And Cause-Specific Mortality In Gambling Disorder: Evidence From A Nation-Wide Matched And Sibling Cohort Study In Taiwan, Yang-Chieh Brian Chen, Chih-Wei Hsu, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background and aims: Gambling disorder (GD) has been linked to suicidal ideation and suicide deaths; however, evidence on all-cause and cause-specific mortality-particularly in Asian populations-remains limited. Using a retrospective cohort study based on nationwide matched and sibling cohort, we investigated all-cause and cause-specific mortality risk in patients with GD.

Design, setting and participants: A retrospective cohort study was conducted using 2000-2022 data from Taiwan's National Health Insurance Research Database. A cohort of 961 individuals diagnosed with GD was identified. An age- and sex-matched control cohort (n = 3,844) and an unaffected sibling cohort (n = 675) were constructed. Cumulative survival …

Hyperadhesive Von Willebrand Factor Contributes To Pathogenesis Of Preeclampsia, Yajuan Wang, Chenyu Wang, Katie L Houck, Xiaoli Gao, Yuanyuan Chen, Xin Xu, Xue Zhao, Miguel A Cruz, Shu Zhang, Chester Q Li, Fengxia Xue, Min Li, Swati Shree, Jing-Fei Dong, Cha Han

Children’s Nutrition Research Center Staff Publications

Background: Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.

Methods: We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.

Results: We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly …

Clinical Machine Learning Model For Predicting Pathological Complete Response In Patients With Esophageal And Gastroesophageal Junction Adenocarcinoma After Trimodality Therapy, Katsuhiro Yoshimura, Jenny J Li, Rebecca E Waters, Mariela Blum Murphy, Masaaki Iwatsuki, Wayne L Hofstetter, Aileen Chen, Ying Yuan, Jaffer A Ajani

Faculty, Staff and Student Publications

Background: Accurate prediction of pathological complete response (pCR) after preoperative chemoradiation therapy, followed by surgery (trimodality therapy) in esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC) may improve clinical decision-making and patient counseling before esophagectomy. This study aimed to develop predictive models for pCR after trimodality using machine learning (ML) approaches.

Patients and methods: A total of 569 patients with EAC and GEJAC who received trimodality therapy at MD Anderson Cancer Center between 2002 and 2022 were included. Clinicopathological characteristics and survival benefit of patients who achieved a pCR were reviewed via descriptive and survival analyses. Subsequently, ML models based …

Safety And Efficacy Of Tranexamic Acid In Urologic Surgery: Results From The International, Randomized, Placebo-Controlled Poise-3 Trial, Flavia K Borges, Farhad Tondroanamag, Tuomas P Kilpeläinen, Sara V Tornberg, Thomas W Painter, David Conen, Vladimir Lomivorotov, Daniel I Sessler, Matthew T V Chan, Maria Jose Martinez-Zapata, Chew Y Wang, Denis B Xavier, Michael K Wang, Wojciech Szczeklik, Kate Leslie, Luke T Lavallee, Rodney H Breau, Kumar Balasubramanian

Faculty, Staff and Student Publications

Background and objective: Perioperative bleeding is common. Evidence for tranexamic acid (TXA) in urology remains limited and conflicting, and major urologic guidelines provide no recommendations. In an a priori planned analysis, we evaluated TXA among patients undergoing urologic surgery in POISE-3.

Methods: POISE-3 was an international randomized trial of patients undergoing surgery with bleeding and cardiovascular risk factors. Participants received TXA (1 g intravenous bolus at surgery start and end) or placebo. The primary efficacy outcome was a 30-day bleeding composite (life-threatening/major/critical organ), and the primary safety outcome was a 30-day thrombosis composite (myocardial injury after noncardiac surgery [MINS], nonhemorrhagic …

Language Serving Hospitals And Their Impact On Readmission For Surgical Patients With A Non-English Primary Language: A Retrospective Cohort Study, Jesus Mejia, Bryan S Torres, Rachel E Murphy, Nayeli Magana, Regan W Bergmark, Andrea L Pusic, Alicia Fernandez, David W Bates, Gregory L Peck, Gezzer Ortega

Faculty, Staff and Students Publications

Objective: To assess postoperative readmission for patients with non-English primary language (NEPL) at language-serving hospitals (LSHs) versus non-LSH.

Background: Patients with NEPL have worse surgical outcomes compared to patients with an English primary language. Hospital-level language access resources vary, potentially leading to disparate health outcomes.

Methods: We performed a retrospective cohort study from 2010 to 2022 using the New Jersey AHRQ-Healthcare Cost and Utilization Project State Inpatient Database. Patients with a primary language variable seen at a hospital that met LSH or non-LSH criteria were identified. Patients with NEPL who underwent appendectomy, breast surgery, cholecystectomy, colectomy, or lower extremity arterial …

Vitamin B6 Predicts Poor Outcomes In Geographically Distinct Populations With Primary Sclerosing Cholangitis, Brian D Juran, Elizabeth J Atkinson, Erik M Schlicht, Jackie K Bianchi, Bryan M Mccauley, Sara K V Tjønnfjord, Hólmfríður Helgadottir, Per M Ueland, Arve Ulvik, Peter Sauer, Trine Folseraas, Tom H Karlsen, Mette Vesterhus, Michael T Dill, Konstantinos N Lazaridis, Johannes R Hov

Faculty, Staff and Students Publications

Background & aims: Primary sclerosing cholangitis (PSC) has a variable disease course, complicating patient counseling and the timing of liver transplantation. Vitamin B6 deficiency predicts reduced liver transplantation-free survival in Scandinavian PSC cohorts. Here, we aimed to validate this observation in US and German PSC cohorts and to expand our analyses to include hepatic decompensation as a clinical outcome.

Methods: Serum active vitamin B6 (pyridoxal 5'-phosphate [PLP]) was analyzed using liquid chromatography-tandem mass spectrometry in retrospective cohorts of people with PSC from Norway (n = 315), the USA (n = 756), and Germany (n = 149). Cox proportional hazards and …