Digital Commons Network^™

Indications, Techniques, And Safety Of Cryotherapy And Cryobiopsy Via Flexible Bronchoscopy In Pediatric Patients, Alex J Katz, Haley Haskett, Kubra M Bozkanat, Aoife Corcoran, Lauren M C Grant, Antoinette Wannes Daou, Sin Tran, Esra Caylan, Alfin Vicencio, Dan T Benscoter, Cherie A Torres-Silva, Sara M Zak, Gregory Burg, Lisa R Young, Pelton Phinizy, Shailendra Das, Richard Paul Boesch, Erik B Hysinger, Joseph Piccione

Faculty, Staff and Students Publications

Rationale: Cryotherapy and its diagnostic analogue, cryobiopsy, are emerging techniques via bronchoscopy with a wide range of clinical applications. While the use of cryotherapy and cryobiopsy has been established in adult pulmonary medicine, pediatric data describing the indications, procedural specifics, outcomes, and complications are limited.

Objective: To describe the indications, procedural specifics, outcomes, and complications of cryotherapy and cryobiopsy use in pediatric bronchoscopy.

Methods: A multicenter retrospective observational study was conducted at 5 pediatric hospitals in the United States. Patients aged 0 to 21 years who underwent cryotherapy or cryobiopsy via bronchoscopy between January 2017 and January 2025 were included. …

Proteomic Signatures Of 3-Year Progression From Impaired Fasting Glucose To Diabetes: The Atherosclerosis Risk In Communities (Aric) Study, Mary R Rooney, Justin B Echouffo Tcheugui, Jingsha Chen, Keenan A Walker, Christie M Ballantyne, Eric Boerwinkle, Tanika N Kelly, Chiadi E Ndumele, James S Pankow, Morgan E Grams, Wendy S Post, Peter J Ganz, Alexis C Wood, Jerome I Rotter, Elizabeth Selvin, Josef Coresh

Faculty, Staff and Students Publications

Objective: To identify proteomic signatures underlying 3-year progression from impaired fasting glucose (IFG) to diabetes.

Research design and methods: We examined IFG progression in the Atherosclerosis Risk in Communities (ARIC) study from visit 2 (1990-1992) to visit 3 (1993-1995). We tested associations of 4,955 plasma proteins (SomaScan version 4.0) with ∼3-year progression from IFG (FG 100-125 mg/dL without diabetes) to diabetes (diagnosis, medication, or FG ≥126 mg/dL) using logistic regression models adjusted for demographics, cardiometabolic risk factors, and baseline glucose with Bonferroni correction (P < 10-5). We explored biological pathways enriched among the top proteins and calculated improvements in prediction (ΔAUC and net reclassification using 3-year risk thresholds of 6% and 15% in 80% training and 20% internal validation subsamples). We validated results in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

Results: There were 3,786 ARIC participants with IFG (mean [SD] age 57 [6] years, 52% female, …

Rates Of, Reasons For, And Reactions To Discontinuation Of Glp-1 Receptor Agonists: A Narrative Review, Henry D Heisey, L Parker Gregg, Christopher D Verrico, Dennis T Villareal, Terri L Fletcher

Faculty, Staff and Students Publications

GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual …

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%; …

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 …

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 …

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 …

Decision-Making Criteria In Polygenic Embryo Screening: A Survey Of Reproductive Medicine Physicians, Rémy A Furrer, Aayushi Gandhi, Dorit Barlevy, Shai Carmi, Todd Lencz, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) examines embryos for their genetic likelihood of developing complex conditions and traits. The commercialization of PES places reproductive endocrinologists and infertility specialists (REIs) as the primary decision-makers in its use, despite professional guidelines cautioning that PES is not ready for clinical use.

Methods: This survey examines how 152 US REIs perceive and approach potential clinical decision-making scenarios regarding the use of PES.

Results: REIs were more likely to offer PES for medical conditions (up to 62% for cancer) than for traits (eg, 0% for skin color, 10% for body mass index). When evaluating 11 potential …

Diabetter Together: Outcomes Of A Randomized Controlled Trial Evaluating A Peer Mentor Behavioral Intervention For Young Adults With Type 1 Diabetes During The Transfer From Pediatric To Adult Care, Marisa E Hilliard, Charles G Minard, Samantha A Carreon, Wendy L Levy, Sarah K Lyons, Randi Streisand, Tricia S Tang, Siripoom V Mckay, Sridevi Devaraj, Barbara J Anderson

Faculty, Staff and Students Publications

Objective: Transition between pediatric and adult health care is complex, with high risk for loss to follow-up and suboptimal health outcomes for young adults with type 1 diabetes. This trial evaluated the efficacy of DiaBetter Together, a 12-month strengths-based behavioral intervention delivered by trained peer mentors. The intervention aimed to help young adults navigate the transfer process to promote optimal glycemic outcomes, shorten time to adult care follow-up, and improve psychosocial outcomes.

Research design and methods: Using a single-site randomized clinical trial design, we compared the 12-month intervention to usual care among n = 100 young adults aged 17-25 years …

De Novo Complex Genomic Rearrangement Spanning 2q31.1 In A Proband With Congenital Malformations: Genotype-Phenotype Correlation And Development Of A Cgr Detection Pipeline, Katherine Helle, Jesse D Bengtsson, Mira Gandhi, Christopher M Grochowski, Ming Yin Lun, Neha Sudhir, Shalini N Jhangiani, Fritz J Sedlazeck, Seema R Lalani, Neil A Hanchard, Claudia M B Carvalho

Faculty, Staff and Students Publications

The 2q31 region is commonly associated with pathogenic alleles of the HOXD cluster leading to various clinical phenotypes related to skeletal development. We present a proband with tetralogy of Fallot and multiple congenital anomalies. Genomic variant screening including an in-house CGR detection pipeline pairing genome sequencing (GS) structural variant calls with read-depth data revealed a de novo complex genomic rearrangement (CGR) spanning 2.7 Mb across 2q31 characterized by a series of duplications and triplications including the HOXD gene cluster. The genomic structure was assembled by applying combined methodologies including short-read and long-read GS, and optical genome mapping (OGM). This in-house …

Obsessive-Compulsive Training Experiences In United States (Us) Medical School Education Programs, Carlos Valenzuela-Flores, Leanne Maduka, Dale Shepherd, Megan C Alam, Juliana E Avery, Hannah C Moore, Gian Depamphilis, Megan M Dailey, Caitlin M Pinciotti, Andrew D Wiese, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Objective: To evaluate the content and structure of OCD-specific training within United States osteopathic (D.O.) and allopathic (M.D.) medical schools. Although many physicians encounter patients with obsessive-compulsive disorder (OCD) in clinical practice, limited familiarity with the full range of OCD presentations, including typical and atypical forms, may contribute to misdiagnosis and delays in accurate diagnosis and treatment.

Methods: Respondents from 35 of the 154 (22.73%) medical schools within the United States (28 (80%) allopathic, 7 (20%) osteopathic schools) completed a survey assessing demographics, school information, and OCD-focused training within medical school curriculums. Descriptives were gathered to characterize the level of …

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 …

Ecmo Use In Infants With Bronchopulmonary Dysplasia: A Literature Review., John Ibrahim, Nicholas Carr, Franscesca Miquel Verges, Natalie Rintoul, Robert Digeronimo, John M. Daniel Iv, Sarah Keene, Burhan Mahmood

Manuscripts, Articles, Book Chapters and Other Papers

Bronchopulmonary dysplasia (BPD) is a leading cause of chronic respiratory failure in infants. Severe BPD is associated with prolonged mechanical ventilation, pulmonary hypertension, and high morbidity and mortality. As disease severity increases, extracorporeal membrane oxygenation (ECMO) is being reconsidered as a potential rescue therapy. Historically, ECMO has been reserved for neonates with reversible respiratory failure and those who required mechanical ventilation for less than 14 days, while infants with BPD were excluded. However, advancements in ECMO technology, anticoagulation strategies, and ventilatory management have led to a reassessment of its role in this population. Emerging reports suggest ECMO may serve as …

Pharmvar Genefocus: Cyp1a2-Clinical Impact, Genetic Variation, And Updated Nomenclature., Katalin Monostory, Gonzalo Villapalos Garcia, Dora Koller, Solomon Adams, Chad A. Bousman, Evangelia Eirini Tsermpini, Michelle Whirl-Carrillo, Amy J. Turner, Volker M. Lauschke, Mohamed Nagy, Erin C. Boone, Teri E. Klein, Pablo Zubiaur, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the highly polymorphic human CYP1A2 gene. CYP1A2 plays a crucial role in the biotransformation of several commonly used drugs, including antipsychotics, antidepressants, anxiolytics, and methylxanthines. The activity of CYP1A2 varies significantly among individuals due to genetic and non-genetic factors. This GeneFocus paper offers an overview of the functional significance of CYP1A2 in drug metabolism, CYP1A2 genetic variation, and presents the updated PharmVar star allele-based nomenclature for CYP1A2. Updates include revisions to previously defined star alleles to align with PharmVar standards, as well as the addition of novel star alleles, providing the pharmacogenetic …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Obsessive-Compulsive Disorder In Three Understudied Populations: A Review Of Latino, Black, And Sexual & Gender Minority Individuals, Ryan J Mccarty, Ogechi C Onyeka, Caitlin M Pinciotti, Andrew D Wiese, Eric A Storch

Faculty, Staff and Students Publications

Purpose of review: This review overviews the research base for obsessive-compulsive disorder (OCD) among three historically understudied populations; Latino/Latin Americans, Black/African Americans, and Sexual and Gender Minority individuals.

Recent findings: Findings suggest that while core OCD symptoms are broadly similar across groups, sociocultural factors such as discrimination, minority stress, stigma, family context, spirituality, and access to care significantly influence symptom presentation, severity, and treatment utilization. Recent studies have evaluated assessment tools and provided evidence supporting exposure and response prevention, while emphasizing the importance of culturally responsive assessment and treatment. Large-scale initiatives are also improving representation in OCD research and addressing …

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 …