Digital Commons Network^™

Clinical Machine Learning Model For Predicting Pathological Complete Response In Patients With Esophageal And Gastroesophageal Junction Adenocarcinoma After Trimodality Therapy, Kohei Yamashita, Evan Kwiatkowski, Matheus Sewastjanow-Silva, Jane E Rogers, Katsuhiro Yoshimura, Melissa Pool Pizzi, Qiong Gan, 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, Kari A O Tikkinen, Maura Marcucci, Alex L E Halme, Sandra N Ofori, Flavia K Borges, Charlotte T B Kanstrup, Lily J Park, 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, P J Devereaux

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 …

Fuimos Olvidados Y Descuidados [Forgotten And Neglected]: Lessons Learned And Findings From On-Farm Covid-19 Education And Vaccine Clinics For Agricultural Workers And Their Multigenerational Families In Texas, Anabel Rodriguez, David I Douphrate, Ana L Pineda Reyes, Susana Zavala, Lus Chavez, Sofia Nicole Lopez, Andrea V Cabrera Cruz, Annie J Keeney, Nora Hernandez, Brenda Berumen-Flucker, Eva M Shipp, Matthew W Nonnenmann, Shannon P Guillot-Wright, Bethany Boggess Alcauter, G Lopez Ixta, Paula M Cuccaro, Higinio Fernandez-Sanchez, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

Background: Despite being deemed essential non-healthcare workers, agricultural workers were excluded from COVID-19 vaccine prioritization in Texas. This professional practice report describes the multifaceted worker health and safety approaches to protecting agricultural workers and their families during the COVID-19 pandemic.

Methods: Between March 2020 and January 2025, several outreach, education, and training grants from various funding agencies were leveraged to deliver training, personal protective equipment, vaccines, and economic relief to agricultural workers in partnership with community-based organizations, industry, local public health departments, and academic institutions.

Findings: Timely funding efforts led to the distribution of 1,000 PPE kits, with more than …

Small But Mighty: How Can Pediatric Psychologists Harness The Power Of Digital Single-Session Interventions?, Christina Amaro, Alexandra Monzon, Melissa Alderfer, Kimberly Canter, Michael Amylon, Stephanie Fooks-Parker, Jessica Schleider, Susana Patton, Katie Devine

Department of Pediatrics Faculty Papers

OBJECTIVE: Single-session interventions (SSIs) are an innovative, scalable approach for addressing the unmet behavioral and mental health needs of pediatric patients and their families. Specifically, digital SSIs, which are self-guided and delivered online, offer a low-cost and accessible approach but are currently underutilized in pediatric psychology.

METHODS: This topical review aims to describe SSIs broadly and the specific need for digital SSIs, explore potential applications within pediatric psychology, outline future directions and considerations, and present two examples of community-engaged digital SSI design.

RESULTS: SSIs evidence small to medium effects across a range of mental health concerns, including distress, anxiety, and …

Cyp2c19 C.681g>A Is Not In Complete Linkage Disequilibrium With C.332-23a>G: Implications For Pharmacogenetic Testing., Amy J Turner, Erin C. Boone, Cyrine E Haidar, Wenjian Yang, Ashley D Derezinski, Andrew Haddad, Philip E. Empey, Ulrich Broeckel, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

CYP2C19 plays an important role in the metabolism of many medications, including the antiplatelet agent clopidogrel, the antifungal agent voriconazole, selective serotonin reuptake inhibitors, select tricyclic antidepressants, and proton pump inhibitors. The Clinical Pharmacogenetics Implementation Consortium has published several guidelines emphasizing the importance of CYP2C19 genotype-guided therapy to optimize patient outcomes. Formerly, the no function CYP2C19*2 allele was defined by three variants, c.332-23A>G (splice defect), c.681G>A (splice defect), and c.991A>G (p.I331V). The discovery of two new haplotypes, one containing only a single variant, c.681G>A, and another with only c.681G>A and c.991A>G, challenged the assumption …

A Cooking Skills Intervention For Long-Term Weight Loss In Young Adults With Intellectual Disabilities: Rationale And Design For A Randomized Trial., Lauren T. Ptomey, Jessica C. Danon, Delwyn Catley, Richard A. Washburn, Amy Bodde, Francisco J. Diaz, Brian C. Helsel, Anna M. Rice, Joseph R. Sherman, Madison Koester, Walker S. Mckinney Ph.D., Joseph E. Donnelly

Manuscripts, Articles, Book Chapters and Other Papers

Young adults with intellectual disability (ID) are an underserved population with a high prevalence of obesity, obesity-related health conditions, and reduced ability to complete instrumental and basic activities of daily living (I/ADLs). After leaving the structured environment of public school, many young adults with ID spend more time at home or in day programs, begin living more independently, or enter the workforce. These transitions may increase reliance on fast or processed foods and reduce opportunities for physical activity, contributing to accelerated weight gain. Previous research has demonstrated clinically meaningful short- and long-term weight loss (18-24 months) in adults with mild-to-moderate …

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 …

Leveraging Administrative Health Data To Capture Rare Adverse Drug Reactions: Identifying Pediatric Patients With Trimethoprim-Sulfamethoxazole Acute Respiratory Distress Syndrome., Keith Feldman, Jenna Miller, Katherine Doane, Laura Loftis, James W. Antoon, Kevin J. Downes, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim-sulfamethoxazole causing acute respiratory distress syndrome (TMP-SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP-SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP-SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate …

Are We Winning At Twinning? Persistent Cni Use In Identical Kidney Transplants., Nicholas S. Herrera, Shivani Wadnerkar, Diane M. Cibrik

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcineurin inhibitors (CNIs) revolutionized kidney transplantation by reducing acute rejection rates. Identical twin kidney transplantation is the only setting in which the allograft is immunologically indistinguishable from self, yet CNI use persists. We characterized CNI utilization across end-stage kidney disease etiologies and examined whether CNI exposure was associated with reduced rejection or improved death-censored graft survival (DCGS).

METHODS: We performed a retrospective cohort study using scientific registry of transplant recipients data (January 2000-August 2025). Among 255 adult identical twin kidney transplant recipients, discharge regimens were categorized by CNI use; Firth penalized Cox regression was the primary method for 10-year …

Clinical Pharmacogenetics Implementation Consortium (Cpic) Guideline For Cyp2d6 Genotype And Use Of 5-Ht3 Receptor Antagonists: 2026 Update, Claire Moore, Melissa S. Bourque, Andreas Halman, José A G Agúndez, Cynthia A. Prows, Keiko Hikino, Matthias Schwab, Carolyn J. Oxencis, Dharmisha Chauhan, Meta H M Diekstra, Susie E. Long, Gillian C. Bell, Andrea Gaedigk, Michelle Whirl-Carrillo, Teri E. Klein, Kelly E. Caudle, Rachel Conyers

Manuscripts, Articles, Book Chapters and Other Papers

5-hydroxytryptamine type 3 (5-HT₃) receptor antagonists are used to treat nausea and vomiting and in the prevention of chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting. Most of the 5-HT₃ receptor antagonists (i.e., ondansetron, tropisetron, dolasetron, palonosetron, and ramosetron) are metabolized by CYP2D6, but the extent of CYP2D6 involvement varies. CYP2D6 genetic variation can influence the metabolism of these medications, particularly ondansetron and tropisetron, thereby affecting drug efficacy. This guideline is an update to the 2016 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron and includes updated information on CYP2D6 genetic …

Extending Genome-Wide Association Studies To Admixed Cohorts With High Degrees Of Relatedness, Taotao Tan, Alejandra Vergara-Lope, José Jaime Martínez-Magaña, Nirav N Shah, Yi-Sian Lin, Kai Yuan, Jaime Berumen, Jesus Alegre-Díaz, Pablo Kuri-Morales, Roberto Tapia-Conyer, Joel Gelenter, Janitza L Montalvo-Ortiz, Wei Zhou, Jason M Torres, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

Admixed populations comprise a large portion of the human population worldwide, but are often excluded from genome-wide association studies (GWASs) due to analytic challenges. Our group developed Tractor, a local-ancestry-informed GWAS tool designed for admixed samples that produces accurate ancestry-specific effect sizes and boosts the discovery power to identify ancestry-enriched loci. However, Tractor operates under an assumption of unrelated samples. Here, to address this gap, we propose Tractor-Mix, which allows for well-calibrated association studies in datasets containing admixed samples with relatedness. Extensive simulations show that this method is competitive with other state-of-the-art approaches that do not produce ancestry-specific results. Empirical …

A Blended Genome And Exome Sequencing Method Captures Genetic Variation In An Unbiased And Cost-Effective Manner, Toni A Boltz, Benjamin B Chu, Matthew Defelice, Calwing Liao, Julia M Sealock, Robert Ye, Jacqueline I Goldstein, Lerato Majara, Jack M Fu, Susan K Service, Lingyu Zhan, Sarah E Medland, Sinéad B Chapman, Simone Rubinacci, Jonna L Grimsby, Tamrat Abebe, Melkam Alemayehu, Fred K Ashaba, Elizabeth G Atkinson, Tim B Bigdeli, Amanda B Bradway, Harrison Brand, Lori B Chibnik, Samuel Deluca, Ana M Diaz-Zuluaga, Abebaw Fekadu, Michael Gatzen, Bizu Gelaye, Stella Gichuru, Marissa L Gildea, Toni C Hill, Hailiang Huang, Kalyn M Hubbard, Wilfred E Injera, Roxanne James, Moses Joloba, Christopher Kachulis, Phillip R Kalmbach, Rogers Kamulegeya, Gabriel Kigen, Soyeon Kim, Nastassja Koen, Edith K Kwobah, Joseph Kyebuzibwa, Seungmo Lee, Niall J Lennon, Penelope A Lind, Esteban A Lopera-Maya, Johnstone Makale, Serghei Mangul, Justin Mcmahon, Pierre Mowlem, Henry Musinguzi, Rehema M Mwema, Noeline Nakasujja, Carter P Newman, Lethukuthula L Nkambule, Conor R O'Neil, Ana Maria Olivares, Catherine M Olsen, Linnet Ongeri, Sophie J Parsa, Adele Pretorius, Shengying Qin, Raj Ramesar, Faye L Reagan, Chiara Sabatti, Jacquelyn A Schneider, Welelta Shiferaw, Christine Stevens, Anne Stevenson, Erik Stricker, Rocky E Stroud, Jessie Tang, Megan Townsend, David Whiteman, Mary T Yohannes, Mingrui Yu, Kai Yuan, Dickens Akena, Lukoye Atwoli, Symon M Kariuki, Karestan C Koenen, Charles R J C Newton, Dan J Stein, Solomon Teferra, Zukiswa Zingela, Carlos N Pato, Michele T Pato, Carlos Lopez-Jaramillo, Nelson B Freimer, Roel A Ophoff, Loes M Olde Loohuis, Michael E Talkowski, Benjamin M Neale, Daniel P Howrigan, Alicia R Martin

Duncan NRI Faculty and Staff Publications

Here we developed and deployed the blended genome exome (BGE) method, a DNA library approach that generates low-pass whole-genome (1–4× mean depth) and deep whole-exome (30–40× mean depth) data in a single sequencing run. BGE is cost-effective, empowers most genomic discoveries possible with deep whole-genome sequencing and captures global common single-nucleotide polymorphism diversity. We applied BGE to sequence >53,000 samples from the PUMAS Project (Populations Underrepresented in Mental Illness Associations Studies), including African, African American and Latin American populations. Imputed genotypes showed high concordance with Illumina Global Screening Array calls (R2 ≥ 95% for minor allele frequency ≥1%; …

Hippo Signaling Regulates Cuticle Pigmentation And Dopamine Metabolism In Drosophila, Shelley B Gibson, Samantha L Deal, Ye-Jin Park, Bo Sun, Yanyan Qi, Jung-Wan Mok, Hyung-Lok Chung, Hongjie Li, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise …

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 …

Defining The Value Of Elective Lumbar Fusion: A Systematic Review Of Existing Methodologies And Framework For The Operative Value Index, Advith Sarikonda, Anthony Chen, Theo S. Biddle, Danyal A. Quraishi, Preston Carey, Arbaz A. Momin, Matthews Lan, Dwight Mitchell Self, Ashmal S. Kabani, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

BACKGROUND: Despite wide variation in the outcomes and costs of lumbar fusion, few studies have integrated these domains together within a single metric to assess "value" (outcomes achieved per dollar spent). In this review, we sought to 1) characterize existing metrics of cost-effectiveness for lumbar fusion, 2) evaluate all applications of time-driven activity-based costing (TDABC) in spine surgery, and 3) outline the conceptual foundation for a standardized Operative Value Index (OVI).

METHODS: Two PRISMA-concordant systematic reviews were performed on PubMed and Scopus databases. The first review examined all studies which reported a cost-effectiveness metric for lumbar fusion. The second review …

Select Plasma Oxylipins As Potential Biomarkers Of Effective Indomethacin Treatment Response In Preterm Infants With Patent Ductus Arteriosus., Khanh C K Nguyen, Cindy H T Yeung, Allison Scott, Thomas J. Velenosi, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Patent ductus arteriosus (PDA) is one of the most common heart conditions in preterm infants, and indomethacin treatment is used for PDA closure. However, its efficacy varies among patients. This pilot study aimed to identify novel metabolic biomarkers to predict effective indomethacin response in infants with PDA.

METHODS: Preterm infants with PDA <  34 weeks gestational age were recruited and treated with indomethacin. Plasma and urine samples were collected before and 2-7 days after initial treatment. Longitudinal targeted oxylipin and untargeted metabolomics analysis were performed on plasma and urine samples.

RESULTS: Among 17 infants, 12 were responders and 5 non-responders to indomethacin treatment. Before the treatment, four plasma oxylipins: 12,13-DiHOME, 9,10-DiHOME, 15,16-DiHODE, and 9,10-DiHODE were significantly higher in responders compared to non-responders (P <  0.05). Following treatment, these oxylipins decreased in responders but remained stable in non-responders. Urinary 12,13-DiHOME showed an opposite trend, with lower baseline concentrations in the responders.

CONCLUSIONS: Pre-treatment plasma levels of four oxylipins were associated with effective PDA response to …

"It Doesn't Matter Where Ocd Comes From," Or Does It?, Caitlin M Pinciotti, Ryan J Mccarty, Gabriella T Ponzini

Faculty, Staff and Students Publications

Purpose of review: This review critically evaluates the claim that etiology is not relevant to cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). Research on the clinical presentation and treatment outcomes associated with traumatic/stressor and biological etiologies is presented.

Recent findings: The extant literature demonstrates varying clinical utility across the reviewed etiologies. Traumatic/stressor etiologies show the most consistent and robust evidence of clinical utility, demonstrating compelling associations with clinical presentation and treatment outcomes, while also being amenable to existing evidence-based approaches. Medical conditions (e.g., Pediatric Acute onset Neuropsychiatric Syndrome) and neurobiological factors also demonstrate considerable associations with OCD presentation, yet …

Comment On: Managing Sickle Cell Disease And Related Complications In Pregnancy: Results Of An International Delphi Panel, Deva Sharma, Ilknur Pamuk, Kenneth I. Ataga, Alexandra Benachi, Selim Büyükkurt, Sophie Lanzkron, Hakan Ozdogu, Shivan Pancham, Lydia H. Pecker, Susan E. Robinson, Safak Yilmaz Baran

Cardeza Foundation for Hematologic Research

Consensus-based recommendations on managing sickle cell disease in pregnancy were recently published in a hematology journal. As this topic is also of great interest to obstetricians and gynecologists, we summarize some of these recommendations, while highlighting the challenges of providing evidence-based medical care to pregnant individuals with sickle cell disease.

Notch Signaling Regulates The Secretion Of Pro-Metastatic Factors In Extracellular Vesicles In Liposarcoma, Menchus Quan, Yi-Kai Liu, Ying Zhao, Madeline Kay, Kai Sun, Timothy P Gavin, Raphael E Pollock, W Andy Tao, Shihuan Kuang

The Brown Foundation: Institute of Molecular Medicine

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that …

Ophthoevidence Report: Comparative Effects Of Prophylactic Strategies For Post-Intravitreal Injection Endophthalmitis: Protocol For A Systematic Review And Network Meta-Analysis, Maryam Ghadimi, Dena Zeraatkar, João Pedro Lima, Jinhui Ma, Sunir J. Garg, Peter Kaiser, David Steel, Tien Yin Wong, Sobha Sivaprasad, Charles Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

BACKGROUND: Endophthalmitis is a rare but serious complication of intravitreal injections (IVI). To mitigate the risk of post-injection endophthalmitis (PIE), retinal specialists use different strategies, combining various prophylactic measures. However, existing systematic reviews have evaluated the effects of these measures in isolation, which does not consider their concurrent use in practice. A trustworthy systematic review with network meta-analysis (NMA) by providing a framework for simultaneous comparisons of different prophylactic combinations is essential to guide decision-making.

OBJECTIVES: To present a protocol for addressing the comparative effects of different strategies for the prevention of PIE.

METHODS: We will search Medline, EMBASE, Cochrane …

De Novo Pyrimidine Synthesis Controls Germinal Center B Cell And Plasma Cell Fates And Systemic Autoimmunity, Julia L. Weber, Tien Bui, Keomonyroth Nuon, Adam J. Fike, Sophia M. Crocker, Kristen N. Bricker, Anju Maharjan, Wujuan Zhang, Aaron R. Goldman, Sathi Babu Chodisetti, Ziaur S. M. Rahman

Department of Microbiology and Immunology Faculty Papers

Whether and how pyrimidine metabolites promote systemic autoimmunity is unknown. Here, metabolomics and 15N-amide glutamine tracing show enhanced flux through de novo pyrimidine synthesis in systemic lupus erythematosus (SLE)-prone B cells. Temporal inhibition of pyrimidine synthesis dampens SLE-prone but not foreign antigen-specific germinal center (GC), plasma cell (PC), and antibody responses. Uridine monophosphate synthase (UMPS) conditional deletion, however, reveals a B cell-intrinsic requirement of de novo pyrimidine synthesis in foreign antigen-driven and SLE-prone GC, PC, and antibody responses and kidney immune complex deposition. Metabolomics, mitochondrial stress test, metabolic flow cytometry, glycolytic rate assay, and RNA sequencing highlight the importance of …

From Chromosomes To Precision Therapy: Clinical Cytogenetics And Cytogenomics In The Era Of Genomic Medicine, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Under Pressure: Negative Urgency And Disordered Eating In The Context Of Parental Differential Support, Hamide Gozu, Jenna K. Rieder

College of Humanities and Sciences Faculty Papers

Disordered eating behaviors are prevalent in emerging adulthood and may be shaped by family dynamics. This study examined associations among maternal and paternal differential support, weight-shape concerns, and binge eating and compensatory behaviors in emerging adulthood, while testing the moderating role of negative urgency. Participants were 517 emerging adults from across the United States (ages 18-29; M = 22.60, SD = 3.81; 76% female). Participants reported on parental differential support, weight-shape concerns, eating behaviors, and negative urgency. Using moderated-mediation analyses, we found that weight-shape concerns mediated associations between differential support and eating behaviors. Unequal maternal support and paternal favoritism showed …

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun

The Brown Foundation: Institute of Molecular Medicine

Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, but the role of macrophage-intrinsic extracellular proteolysis in immunometabolic regulation remains unclear. Matrix metalloproteinase-14 (MMP14), a membrane-bound protease, is strongly induced during monocyte-to-macrophage differentiation and further elevated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacological inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, phagocytosis, and inflammatory activation in response to obesity-associated adipose tissue signals. Mechanistically, MMP14 promoted inflammatory programming by increasing endotrophin generation and enhancing TLR4-NFκB signaling. MMP14 also reprogrammed macrophage lipid metabolism by suppressing lipolysis and promoting lipid accumulation, altering metabolic communication with neighboring …

Acalabrutinib Monotherapy As A First-Line Treatment For Cll: 3 Years Follow-Up Of The Real-World Epic Study: 3-Year Follow-Up Of The Real-World Epic Study, Toby A. Eyre, Nicolás Martínez-Calle, Shankara Paneesha, Mohsen Norouzi, David L Tucker, Harriet Sarah Walter, Alison Boden, Mari Kilner, Neil Phillips, Piers Em Patten, Nimish Shah, Meghna Ruparelia, Sharon Oddy, Tan Tsawayo, Francesco Forconi, Helen Wardle, Tobore Gbemre, Chris Gregory, Lucy B. M. Cook, David J Allsup, Anna Morris, Christopher J C Knechtli, Jenni Davies, Joy Galani, Helen Marr, Claire Hutchinson, Stella Williams, Joe Hickey, Hannah Harding, Sukhjit Hunjan

Peninsula Medical School

Clinical trials indicate that acalabrutinib, a second-generation Bruton tyrosine kinase inhibitor, is safe and effective for treating patients with chronic lymphocytic leukemia (CLL), but real-world evidence on its clinical effectiveness is limited. This ongoing multicenter retrospective chart review included UK adults with previously untreated CLL who received acalabrutinib monotherapy as part of a UK-wide early access program. These patients received their first dose of acalabrutinib between 1 April 2020 and 1 April 2021. Data from 282 patients (male patients, n = 156 [55%]) collected from 29 sites across the United Kingdom revealed a median age of 73.9 years (interquartile range …

Technology Platform (Peer Plus) Supporting The Work Of Peer Recovery Coaches And The Communication Needs Of Individuals In Recovery From Substance Use Disorder: Protocol For An R21 Development And Usability Trial., Amanda Coupe, Jessica Pater, Rachel Pfafman, Victor P Cornet, Elisabeth Andrews, Mindy Flanagan, Dana Albright, Abhinay Balasani, Christopher Becker, Brian Parise, Erik Hess, Tammy Toscos

Health Services and Informatics Research

BACKGROUND: Substance use disorder (SUD) represents a significant public health concern in the United States. SUD recovery is complex and individualized, and support provided by peer recovery coaches (PRCs) can improve outcomes. The PRC-client relationship requires bidirectional mediated communication that is often informal but should be trackable, efficient, and aligned with health care privacy and security regulations. Current workflows and available apps do not meet these needs, illustrating the opportunity for client-centered technology tools. We have developed Peer PLUS (People Leveraging Urgent Support; Parkview Health System, Inc), a HIPAA (Health Insurance Portability and Accountability Act)-compliant mobile app and client management …

The Biological Response Of Human Np Cells To Soluble Collagen Vi, Jonathan Dalton, Srikanth N. Divi, Yasmine Eichbaum, Panya Luksanapruksa, Mitchell K. Ng, Rachel Huang, Alan S. Hilibrand, Alex R. Vaccaro, Dessislava Z. Markova, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

Extracellular matrix (ECM) dysregulation plays a significant role in the development of intervertebral disc disease (IVDD). The ECM around the chondrocytes in the nucleus pulposus (NP) is unique in that it contains ColVI. While linked to chondrocyte proliferation in cartilage, ColVI's specific role in IVD degeneration is less clear. Our aim was to determine the expression of ColVI in NP cells from degenerative IVDs, along with the effects of soluble ColVI on NP cells. Thus, we compared the expression levels of ColVI in human degenerated IVD samples, along with the effect of soluble ColVI on primary human NP cells. A …

Effects Of Non-Surgical Periodontal Therapy On Dental Plaque Microbiome, Qingguo Wang, Bing-Yan Wang, Derek Wilus, Hua Xie

Faculty, Staff and Student Publications

Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3–4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced probing …

Neural-Immune-Cardiovascular Axis: From Mechanistic Crosstalk To Therapeutic Targets In Cardiovascular Disease, Junkang Cheng, Shuang Gao, Haowei Zhang, Wei Gao, Zeyuan Mei, Xiaoling Liu, Jocelyn Gao, Chenghu Guo, Guipeng An

Student Papers, Posters & Projects

The neural-immune-cardiovascular axis represents an emerging and highly integrated physiological and pathophysiological concept, describing a complex bidirectional communication network between the nervous, immune, and vascular systems. This review systematically examines the pivotal role of this axis in maintaining cardiovascular homeostasis and in the pathogenesis of cardiovascular diseases. We first provide an overview of the fundamental signaling pathways between the components of this axis. Subsequently, we delve into the specific crosstalk mechanisms within the axis in the context of major cardiovascular conditions, including atherosclerosis, hypertension, and heart failure. A central focus is placed on critically evaluating the potential therapeutic targets and …