Medicine and Health Sciences Commons^™

Pka-Driven Spp1 Activation As A Novel Mechanism Connecting The Bone Microenvironment To Prostate Cancer Progression, Pablo Sanchis, Agustina Sabater, Julia Lechuga, Jimena Rada, Rocio Seniuk, Gaston Pascual, Mora Gatti, Juan Bizzotto, Peter D A Shepherd, Jun Yang, Javier Cotignola, Elba Vazquez, Joaquin Mateo, Pia Valacco, Estefania Labanca, Christopher Logothetis, Geraldine Gueron, Nicolas Anselmino

Faculty, Staff and Student Publications

Prostate cancer (PCa) bone metastasis (BM) poses a significant clinical challenge due to the heterogeneity of treatment responses and patient outcomes. In this study, we examined the role of Protein Kinase A (PKA) signaling in modulating the expression of osteopontin (SPP1/OPN), a protein associated with poor prognosis, within a subset of PCa BM patients. By integrating multi-omics results we identified a novel mechanism in which bone-derived type-I collagen (Col1a1) and fibronectin (Fn1) stimulate SPP1 expression in PCa cells through the activation of PKA signaling. This bone-induced regulation of SPP1 was confirmed both in vitro, using PCa-bone co-culture systems (PC3 or …

Alterations In Region-Specific Gray Matter Volume Underlying Callous Unemotional Traits In Adolescents, Johannah Bashford-Largo, Ru Zhang, R James R Blair, Karina S Blair, Jaimie Elowsky, Matthew Dobbertin, Ahria J Dominguez, Melissa Hatch, Tyler Patrick, Sahil Bajaj

Faculty, Staff and Student Publications

Background: Callous-unemotional (CU) traits during adolescence, for example, shallow affect or lack of remorse, have been shown to be a risk marker for antisocial behavior. Only a few studies have investigated structural brain alterations underlying CU traits, and findings are inconclusive. The study examines CU symptomatology and gray matter volume (GMV) associations.

Methods: Structural brain MRI data were collected from a sample of 578 adolescents (60% male) with a mean age of 14.85 years (SD = 2.30; range = 10-19 years). CU traits were indexed via the Inventory for Callous Unemotional Traits (ICU). Region-wise volumetric parameters were obtained following parcellation …

Endoscopic Submucosal Dissection For Previously Attempted Colorectal Lesions: An International Multicenter Experience., Suchapa Arayakarnkul, Hiroyuki Aihara, Alessandro Repici, Roberta Maselli, Antonio Capogreco, Leonardo Da Rio, Fabio Shiguehissa Kawaguti, Fauze Maluf-Filho, Makoto Nishimura, Sera Satoi, Sayaka Nagao, Shai Friedland, Robert Bechara, Norio Fukami, Sonmoon Mohapatra, Amit Bhatt, Abel Joseph, Alex Schlachterman, Anand Kumar, Andrew Y Wang, Ross C D Buerlein, Louis M Wong Kee Song, Fnu Deepali, Dennis Yang, Muhammad K Hasan, Nikhil A Kumta, David L Diehl, Edward J Despott, Alberto Murino, Alessandro Rimondi, Laura Lucaciu, Neil R Sharma, Christina Zelt, Ashley Rumple Rn, Bsn, David Leslie Carr-Locke, Reem Z Sharaiha, Srihari Mahadev, Kamal M Hassan, Mohamad-Noor Abu-Hammour, Carlos Robles-Medranda, Martha Arevalo-Mora, Juan Alcivar-Vasquez, Vivek Kumbhari, Jongkyu Park, Salmaan Jawaid, Mai A Khalaf, Kasenee Tiankanon, Sarah S Al Ghamdi, Mohamed O Othman, Saowanee Ngamruengphong

PCI Publications and Projects

BACKGROUND & AIMS: Salvage endoscopic submucosal dissection (ESD) has been proposed for previously attempted colorectal lesions (PACLs), yet the extensive submucosal fibrosis impacts procedural difficulty and resection outcomes. The aim of this study was to evaluate the efficacy and safety of salvage ESD for the treatment of PACLs.

METHODS: This international, multicenter study enrolled consecutive patients who underwent ESD to manage PACLs. Rates of en bloc, R0 resection, and local recurrence were assessed for efficacy. Safety was assessed by adverse events (AEs), procedure-related mortality, and the need for surgical management.

RESULTS: Of 415 lesions, en bloc rate was 83.4%, the …

Engagement In And Correlates Of Total Cutaneous Exams And Skin Self-Exams Among Young Melanoma Survivors And Their Family, Sharon L Manne, Deborah A Kashy, Sherry Pagoto, Susan K Peterson, Carolyn J Heckman, Joseph Gallo, Adam Berger, David B Buller, Alexandria Kulik, Sara Frederick, Morgan Pesanelli

Faculty, Staff and Student Publications

Young adult melanoma survivors and their close family (first degree relatives/FDRs) are at increased risk for developing a melanoma, but little is known about engagement in and correlates of their clinical skin exam (CSE) and skin self-examination (SSE) behaviors. Five hundred and seventy-four YA survivors and their FDRs completed an online survey assessing engagement in CSE and SSE, as well as measures of background factors, cognitive and psychosocial factors, CSE and SSE planning, and family influences. Approximately 90% of YAs had a CSE and 90% performed SSE in the last year, but engagement in CSE among FDRs was lower (63.2%, …

Is Bedtime Use Of Kratom (Mitragyna Speciosa) A Sleep Aid Or Disruptor? Examining Its Daily Effects And Individual Differences, Chung Jung Mun, Patricia Timmons, Leigh V Panlilio, Christopher D Verrico, Ynhi T Thomas, C Austin Zamarripa, David H Epstein, Kirsten E Smith

Faculty, Staff and Students Publications

Kratom (Mitragyna speciosa) is a psychoactive botanical native to Southeast Asia increasingly used in the U.S. for various self-reported benefits, including sleep improvement. However, empirical evidence concerning kratom’s effects on sleep is limited. Here, we examined the association between bedtime kratom use and self-reported sleep outcomes in naturalistic settings across consecutive days, while also exploring sex and chronic pain status as potential moderators. A secondary analysis was conducted using the data from a 15-day ecological momentary assessment (EMA) study of 357 U.S. adults who reported regularly using kratom. Participants made daily reports of their bedtime kratom use and …

Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin

Faculty, Staff and Students Publications

Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …

Exploring Patients' Perceptions Of An Advance Care Planning Intervention In The Emergency Department: A Qualitative Study, Youkie Shiozawa, Saaya Morton, Nanako Shirai, Hannah Oelschlager, Lucy Kiernat, Anita N Chary, Anna C Revette, Adrian Haimovich, Smit Desai, Kai-Wei Chang, Shan W Liu, Maura Kennedy, Mara A Schonberg, Kei Ouchi

Faculty, Staff and Students Publications

Objectives: Emergency department (ED) visits offer opportunities for seriously ill patients to formulate future medical care goals, yet ED clinicians lack practical strategies for these conversations. ED GOAL, a behavioral intervention, engages seriously ill yet clinically stable older adults in the ED to address advance care planning (ACP) with their outpatient clinicians. In a randomized trial, goals-of-care documentation was significantly higher in the intervention group compared to controls after three (24.3% vs. 9.9%, p = 0.03) and 6 months (31.4% vs. 12.7%, p < 0.01). This study is a sub-analysis to learn about intervention arm participants' perceived benefits and obstacles of the intervention.

Methods: We conducted semi-structured interviews between October 2022 and August 2024 (N = 52) with intervention-arm patients …

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

Faculty, Staff and Students Publications

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

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

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

The Triglyceride-Glucose Index And Risk Of End-Stage Renal Disease Across Different Durations Of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study, Mi-Sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee

2020-Current year OA Pubs

BACKGRUOUND: This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.

METHODS: We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.

RESULTS: Over 6,967,381 person-years of …

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

Faculty, Staff and Students Publications

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

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

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

Implementation Of A Package Of Emergency Care Interventions And Clinical Outcomes, Corey B Bills, Paul Wesseh, Catherine Cooper, Taylor W Burkholder, Lane Epps, Michael Jaung, Emilie J Calvello Hynes, Alex Mayah, John K Shakpeh, Kayla Enriquez

Faculty, Staff and Students Publications

Importance: Investments in emergency care systems are vital to ensuring universal health coverage and improving health outcomes in low- and middle-income countries.

Objective: To assess whether a package of emergency care interventions is associated with improved patient mortality and clinical care quality.

Design, setting, and participants: This pre-post quality improvement study was conducted at a single urban referral hospital emergency unit (EU) in Monrovia, Liberia, to assess clinical and educational outcomes resulting from the implementation of a package of interventions from January 1, 2018, through June 30, 2019. Final analysis was performed in November 2023. Data from a random subset …

Lp(A) Testing For The Primary Prevention Of Cardiovascular Disease In High-Income Countries: A Cost-Effectiveness Analysis, Jedidiah I Morton, Florian Kronenberg, Magdalena Daccord, Nicola Bedlington, Marius Geanta, Tobias Silberzahn, Zhenyue Chen, Jean-Luc Eisele, Bogi Eliasen, Mariko Harada-Shiba, Marc Rijken, Albert Wiegman, George Thanassoulis, Pia R Kamstrup, Iñaki Gutierrez-Ibarluzea, Pablo Coral, Raul D Santos, Erik Stroes, Michal Vrablik, Gerald F Watts, Christie M Ballantyne, Samia Mora, Børge G Nordestgaard, Kausik K Ray, Stephen J Nicholls, Zanfina Ademi, Lp(A) International Taskforce (Itf) Initiative

Faculty, Staff and Students Publications

Background and aims: Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives.

Methods: We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of …

Visual And Quantitative Interstitial Lung Abnormality Progression In Copdgene, Rachel K Putman, Jonathan A Rose, Ruben San José Estepar, Ann-Marcia C Tukpah, Claire C Cutting, Takuya Hino, Akinori Hata, Mizuki Nishino, Stephen M Humphries, David A Lynch, Edwin K Silverman, Michael H Cho, Ivan O Rosas, George R Washko, Hiroto Hatabu, Raúl San José Estepar, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: Interstitial lung abnormalities (ILAs) are visually identified changes on chest computed tomography (CT) scans that may represent early or mild pulmonary fibrosis. Quantitative interstitial abnormalities (QIAs) measure potential parenchymal lung injury on chest CT scans using an automated algorithm. It is not known if combining these visual and quantitative assessments improves prediction of imaging progression.

Objectives: To assess the utility of quantitative imaging to predict imaging progression of ILAs and adverse clinical outcomes in a cohort of smokers.

Methods: ILA presence, subtypes, and progression, as well as QIAs, were assessed on chest CT scans from participants ∼5 years apart …

Transdiagnostic Correlates Of Family Accommodation In Anxious Youth, Whitney S Shepherd, Erika S Trent, Orri Smarason, Hannah N Sansone, Daphne M Ayton, Amanda Palo, Abigail E Candelari, Wayne K Goodman, Andrew G Guzick, Eric A Storch

Faculty, Staff and Students Publications

Anxiety disorders are common in children and cause significant impairment. Family accommodation, which refers to behavioral changes that family members make to temporarily alleviate a child’s anxiety, has been linked to child anxiety symptom severity. Although emotional vulnerabilities for anxiety such as emotion dysregulation, anxiety sensitivity, and distress intolerance have been associated with family accommodation, research concerning the relationship between these constructs among anxious youth is limited. We hypothesized that these variables would be uniquely and positively associated with family accommodation and would moderate the relationship between anxiety symptom severity and family accommodation. Treatment-seeking child–parent dyads (N = 90; …

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

Faculty, Staff and Students Publications

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

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

Dominant Negative Atp5f1a Variants Disrupt Oxidative Phosphorylation Causing Neurological Disorders, Sara M Fielder, Jessie R Zhang, Liana M Valin, Tara Samson, Sarah Govert, Sara Dacunha, Weimin Yuan, Jian Chen, Jacob Lesinski, Hieu Hoang, Stephanie A Morrison, Eric Tycksen, Dustin Baldridge, Gary A Silverman, Lisa Emrick, William J Craigen, Stephen M Sykes, Tim Schedl, Stephen C Pak, Et Al.

2020-Current year OA Pubs

ATP5F1A encodes the α-subunit of complex V of the respiratory chain, which is responsible for mitochondrial ATP synthesis. We describe 6 probands with heterozygous de novo missense ATP5F1A variants that presented with developmental delay, intellectual disability, and movement disorders. All variants were located at the contact points between the α- and β-subunits. Functional studies in C. elegans revealed that the variants were damaging via a dominant negative genetic mechanism. Biochemical and proteomics studies of proband-derived cells showed a marked reduction in complex V abundance and activity. Mitochondrial physiology studies revealed increased oxygen consumption, yet decreased mitochondrial membrane potential and ATP …

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Aging And The Spectral Properties Of Brain Hemodynamics, Ki Yun Park, Abraham Z Snyder, Manu S Goyal, Timothy O Laumann, John J Lee, Babatunde Adeyemo, Nicholas Metcalf, Andrei G Vlassenko, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

Cerebral glucose metabolism (CMRGlc) systematically decreases with advancing age. We sought to identify correlates of decreased CMRGlc in the spectral properties of fMRI signals imaged in the task-free state. Lifespan resting-state fMRI data acquired in 455 healthy adults (ages 18-87 years) and cerebral metabolic data acquired in a separate cohort of 94 healthy adults (ages 25-45 years, 65-85 years) were analyzed. The spectral properties of the fMRI data were characterized in terms of the relative predominance of slow versus fast activity using the spectral slope (SS) measure. We found that the relative proportion of fast activity increases with advancing age …

Germline Cancer Predisposition Results From The National Cancer Institute-Children's Oncology Group Pediatric Match Trial, Sarah Scollon, Sharon E Plon, Steven Joffe, Jaclyn A Biegel, Shashikant Kulkarni, George Miles, David R Patton, Brent Coffey, Cynthia L Winter, Gregory J Tsongalis, Mark J Routbort, Nilsa C Ramirez, Lauren Saguilig, Jin Piao, Todd A Alonzo, Stacey L Berg, Elizabeth Fox, Brenda Weigel, Douglas S Hawkins, Jeffrey S Abrams, Margaret Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, D Williams Parsons

Faculty, Staff and Students Publications

Purpose: Precision oncology trials have generally focused on tumor testing to identify actionable alterations. The National Cancer Institute-Children's Oncology Group Pediatric MATCH trial incorporated return of germline results to assess feasibility of reporting in a cooperative group setting and characterize germline cancer predisposition in patients with refractory cancers.

Patients and methods: Tumor and blood DNA from patients 1-21 years of age with treatment-refractory solid tumors, non-Hodgkin lymphomas, or histiocytic disorders underwent cancer gene panel sequencing. Clinical germline reports returned to 151 study sites included pathogenic/likely pathogenic (P/LP) germline variants found in 38 cancer predisposition genes (CPGs). European Society of Medical …

Endoglin-Directed Car T Cells Comprehensively Target Tumors In Advanced Sarcomas, Harrison R Berger, Malina Maharana, Jeneffer Mirabal, Lyazat Kurenbekova, Alberto Delaidelli, Atreyi Dasgupta, Ahmed Z Gad, Mohamed F Sheha, Sybrina S Kerr, Ada I Ozcan, Jessica S Morris, Angela M Major, M John Hicks, Mary K Mckenna, Ben K Seon, Matthew L Baker, Poul H Sorensen, Meenakshi Hegde, Jason T Yustein, Nabil Ahmed, Sujith K Joseph

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced sarcomas, which leads to dismal outcomes for children and adults. Although chimeric antigen receptor (CAR) T cells hold promise for treating advanced sarcomas, this approach is constrained by a paucity of effective targets. Our previous clinical study identified endoglin (ENG/CD105), a TGFβ coreceptor, as a target of the endogenous immune response in a patient with sarcoma who exhibited an exceptional response to HER2-targeted CAR T-cell therapy. ENG is expressed on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels and therefore offers comprehensive tumor targeting. Furthermore, ENG knockout in sarcoma cells reduces their …

Pfas Exposure And Postoperative Weight Regain In Adolescents After Bariatric Surgery: Findings From The Teen-Labs Study, Brittney O Baumert, Elizabeth Costello, Zhenjiang Li, Justin R Ryder, Thomas Inge, Todd Jenkins, Stephanie Sisley, Stavra A Xanthakos, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Weight regain following bariatric surgery remains a clinical challenge, with limited understanding of contributing environmental factors. Per- and polyfluoroalkyl substances (PFAS), persistent chemicals linked to metabolic dysfunction, may influence long-term weight trajectories. This study aimed to evaluate associations between PFAS exposure and changes in BMI, percent weight loss, and waist circumference among adolescents after bariatric surgery.

Methods: We included 186 adolescents (mean age: 17.1 years; 76.3% female; 72.0% White) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort who underwent surgery between 2007 and 2012. Anthropometric measurements were collected at baseline and 6, 12, 36, and 60 months post …

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis

Faculty, Staff and Students Publications

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …

Analyzing The Learning Curve Of Vnotes Sacrocolpopexy By The Cumulative Summation Test: A Cohort Study, Wenyu Liu, Nannan Sun, Yuejiao Zhang, Yuyan Li, Weihao Lai, Youjun Zhou, Xiaoming Guan, Juan Liu

Faculty, Staff and Students Publications

Background: The learning curve of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) in the treat of pelvic organ prolapse (POP) is critical yet underexplored. Our objective is to describe the learning curve and surgical complications of vNOTES-SC, taking into account the factors that affect operative time and evaluate the long-term follow-up outcomes of this surgery.

Methods: We conducted a hospital-based cohort study involving patients who underwent vNOTES-SC from June 2017 to May 2024. All surgeries were performed by a single surgeon with over 20 years of surgical experience. This study employed cumulative summation test (CUSUM) analysis to quantify the learning …

Post-Deployment Monitoring Of Ai Performance In Intracranial Hemorrhage Detection By Chatgpt, Eric Rohren, Mohadese Ahmadzade, Sofia Colella, Nina Kottler, Sriyesh Krishnan, Jason Poff, Neelesh Rastogi, Walter Wiggins, Joyce Yee, Carlos Zuluaga, Phil Ramis, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Rationale and objectives: To evaluate the post-deployment performance of an artificial intelligence (AI) system (Aidoc) for intracranial hemorrhage (ICH) detection and assess the utility of ChatGPT-4 Turbo for automated AI monitoring.

Materials and methods: This retrospective study evaluated 332,809 head CT examinations from 37 radiology practices across the United States (December 2023-May 2024). Of these, 13,569 cases were flagged as positive for ICH by the Aidoc AI system. A HIPAA (Health Insurance Portability and Accountability Act) -compliant version of ChatGPT-4 Turbo was used to extract data from radiology reports. Ground truth was established through radiologists' review of 200 randomly selected …

Using Latent Patient-Centered Fear Extinction Profiles To Guide Treatment In Pediatric Ocd, Katherine M Ingram, Eric A Storch, Daniel A Geller, Brent J Small, Sabine Wilhelm, Joseph F Mcguire

Faculty, Staff and Students Publications

Background: While exposure with response prevention (ERP) is the frontline treatment for pediatric obsessive-compulsive disorder (OCD), not all patients benefit. Impairments in extinction learning are implicated in pediatric OCD's etiology and treatment, with impaired pre-treatment extinction learning associated with worse ERP outcomes. However, available methods for assessing patients' difficulties with fear extinction are costly and underdeveloped. In response, we used person-centered profiles to characterize latent fear extinction patterns among youth with OCD, and investigated the degree to which scores on common rating scales correspond to profile membership.

Methods: Youth with OCD (n=98) completed a diagnostic clinical battery followed by a …

Brugia Malayi And Other Filarial Parasite Species In Animals In Areas Endemic For Lymphatic Filariasis In Belitung District, Indonesia, Irina Diekmann, Taniawati Supali, Kerstin Fischer, Elisa Iskandar, Noviani Sugianto, Yossi Destani, Rahmat Alfian, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Brugia malayi is the most common cause of lymphatic filariasis (LF) in Indonesia. A zoophilic ecotype that infects both humans and animals occur in Belitung District in Indonesia. The district received five annual rounds of mass drug administration (MDA) between 2006 and 2010 and passed three transmission assessment surveys (TAS) in subsequent years. However, a survey in five villages in 2021 showed a microfilaria (Mf) prevalence of 2.1% in humans. The reappearance of B. malayi infection in humans may be due to reintroduction from animal reservoirs. The goal of this study was to determine B. malayi prevalence in potential …

Ibrutinib Added To Standard Conditioning And As Maintenance Therapy Following Autologous Hematopoietic Stem Cell Transplantation For Relapsed Or Refractory Activated-B-Cell Type Diffuse Large B-Cell Lymphoma: Primary Analysis Of The Us Intergroup Double-Blind Randomized Phase Iii Study Alliance A051301/Bmt-Ctn 1201, Charalambos Andreadis, Brad S Kahl, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (

Peroxisomal Metabolism Of Branched Fatty Acids Regulates Energy Homeostasis, Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N Finck, Mohamed Zayed, Jonathan R Brestoff, Ali Javaheri, Fong-Fu Hsu, Clay F Semenkovich, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Microglia Regulate Gabaergic Neurogenesis In Prenatal Human Brain Through Igf1, Diankun Yu, Samhita Jain, Andi Wangzhou, Beika Zhu, Wenyuan Shao, Elena J Coley-O'Rourke, Stacy De Florencio, Jaeyeon Kim, Jennifer Ja-Yoon Choi, Mercedes F Paredes, Tomasz J Nowakowski, Eric J Huang, Xianhua Piao

2020-Current year OA Pubs

GABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans