Digital Commons Network^™

Heterozygous Midnolin Knockout Attenuates Severity Of Nonalcoholic Fatty Liver Disease In Mice Fed A Western-Style Diet High In Fat, Cholesterol, And Fructose, Soo-Mi Kweon, Jose Irimia-Dominguez, Gayeoun Kim, Patrick T Fueger, Kinji Asahina, Daniela S Allende, Chih-Hong Lou, Walter M Tsark, Ju Dong Yang, Dominic S Ng, Ju-Seog Lee, Patrick Tso, Wendong Huang, Keane K Y Lai

Faculty, Staff and Student Publications

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first …

Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib In Previously Untreated Egfr-Mutated Metastatic Non-Small-Cell Lung Cancer (Relay): Exploratory Analysis Of Next-Generation Sequencing Results, E B Garon, M Reck, K Nishio, J V Heymach, M Nishio, L Paz-Ares, S Ponce Aix, H Graham, B D Butts, C Visseren-Grul, K Nakagawa

Faculty, Staff and Student Publications

Background: Ramucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identify clinically relevant alterations in circulating tumor DNA (ctDNA) and explore their impact on treatment outcomes.

Patients and methods: Eligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks. Liquid biopsies were to be prospectively collected at baseline, cycle 4 (C4), and …

Predicting Severity Of Radiation Induced Lymphopenia In Individual Proton Therapy Patients For Varying Dose Rate And Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations, Lucas Mccullum, Jungwook Shin, Stella Xing, Chris Beekman, Jan Schuemann, Dan Duda, Steven H Lin, Camilo M Correa-Alfonso, Sean Domal, Julia Withrow, Wesley Bolch, Harald Paganetti, Clemens Grassberger

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters.

METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute …

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From The Integral-Ilcco Cohort Analysis, Chao Cheng, Wei Hong, Yafang Li, Xiangjun Xiao, James Mckay, Jinyoung Byun, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John K Field, Michael P A Davies, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Meng Zhu, Hongbing Shen, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Paul Brennan, Yong Li, Olga Gorlova, Ivan Gorlov, Christopher I Amos, Integral-Ilcco Lung Cancer Consortium

Faculty, Staff and Student Publications

INTRODUCTION: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer.

METHODS: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls.

RESULTS: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal …

Gwas-Identified Telomere Length Associated Genetic Variants Predict Risk Of Recurrence Of Hpv-Positive Oropharyngeal Cancer After Definitive Radiotherapy, Peng Sun, Peng Wei, Hongliang Liu, Jia Wu, Neil D Gross, Qingyi Wei, Mark E Zafereo, Jisheng Liu, Guojun Li

Faculty, Staff and Student Publications

Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).

Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.

Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk …

Single-Cell Transcriptomic Analysis Uncovers Intratumoral Heterogeneity And Drug-Tolerant Persister In Alk-Rearranged Lung Adenocarcinoma, Hoi-Hin Kwok, Huiyu Li, Jiashuang Yang, Junyang Deng, Nerissa Chui-Mei Lee, Alva Ko-Yung Sit, Stephanie Kwai-Yee Ma, Lydia Wai-Ting Cheung, Luc Girard, Junya Fujimoto, Ignacio Ivan Wistuba, Boning Gao, John Dorrance Minna, David Chi-Leung Lam

Faculty, Staff and Student Publications

No abstract provided.

Brief Report: Safety And Antitumor Activity Of Durvalumab Plus Tremelimumab In Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced Nsclc: Results From A Phase 1b Clinical Trial, Edward B Garon, Alexander I Spira, Sarah B Goldberg, Jamie E Chaft, Vassiliki Papadimitrakopoulou, Scott J Antonia, D Ross Camidge, John D Powderly, Antoinette J Wozniak, Enriqueta Felip, Song Wu, Maria L Ascierto, Nairouz Elgeioushi, Mark M Awad

Faculty, Staff and Student Publications

Introduction: Although first-line immunotherapy approaches are standard, in patients with non-small cell lung cancer (NSCLC) previously treated with programmed cell death protein-1 or programmed death-(ligand)1 (PD-[L]1) inhibitors, the activity of combined CTLA-4 plus PD-(L)1 inhibition is unknown. This phase 1b study evaluated the safety and efficacy of durvalumab plus tremelimumab in adults with advanced NSCLC who received anti-PD-(L)1 monotherapy as their most recent line of therapy.

Methods: Patients with PD-(L)1-relapsed or refractory NSCLC were enrolled between October 25, 2013, and September 17, 2019. Durvalumab 20 mg/kg plus tremelimumab 1 mg/kg was administered intravenously every 4 weeks for four doses, followed …

Cell-Type-Specific Prediction Of 3d Chromatin Organization Enables High-Throughput In Silico Genetic Screening, Jimin Tan, Nina Shenker-Tauris, Javier Rodriguez-Hernaez, Eric Wang, Theodore Sakellaropoulos, Palaniraja Thandapani, Iannis Aifantis, David Fenyö, Bo Xia, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of cell-type-specific chromatin organization using DNA sequence and two cell-type-specific genomic features-CTCF binding and chromatin accessibility. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. We further developed an in silico genetic screening approach to assess how individual DNA elements may contribute to chromatin organization and …

Retrospective Analysis Of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study By The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Sangkyu Noh, Carolyn Nessim, Emily Z Keung, Christina L Roland, Dirk Strauss, Marco Fiore, Stefano Piero Bernardo Cioffi, Winta Mehtsun, Ferdinando Carlo Maria Cananzi, Federico Sicoli, Vittorio Quagliuolo, Jun Chen, Chenghua Luo, Rebecca A Gladdy, Carol Swallow, Wendy Johnston, Samuel J Ford, Caroline Evenden, Fabio Tirotta, Max Almond, Laura Nguyen, Piotr Rutkowski, Maria Krotewicz, Elisabetta Pennacchioli, Kenneth Cardona, Adriana Gamboa, Daphne Hompes, Marleen Renard, Attila Kollár, Christoph O Ryser, Nikolaos Vassos, Chandrajit P Raut, Mark Fairweather, Dagmar Adamkova Krakorova, Sergio Quildrian, Andraz Perhavec, Eran Nizri, Jeffrey M Farma, Stephanie H Greco, Bruno Vincenzi, José Antonio González Lopez, Mireia Solans Solerdecoll, Shintaro Iwata, Suguru Fukushima, Teresa Kim, Francesco Tolomeo, Hayden Snow, Ynez Howlett-Jansen, Dimitri Tzanis, Maxim Nikulin, Alessandro Gronchi, Jason K Sicklick, Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Faculty, Staff and Student Publications

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas.

BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series.

METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management.

RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of …

Tmbim6 Deficiency Leads To Bone Loss By Accelerating Osteoclastogenesis, Sun-Ju Yi, You-Jee Jang, Seokchan Lee, Sung-Jin Cho, Kyuho Kang, Han-Jung Chae, Kyunghwan Kim

Faculty, Staff and Student Publications

TMBIM6 is an endoplasmic reticulum (ER) protein that modulates various physiological and pathological processes, including metabolism and cancer. However, its involvement in bone remodeling has not been investigated. In this study, we demonstrate that TMBIM6 serves as a crucial negative regulator of osteoclast differentiation, a process essential for bone remodeling. Our investigation of Tmbim6-knockout mice revealed an osteoporotic phenotype, and knockdown of Tmbim6 inhibited the formation of multinucleated tartrate-resistant acid phosphatase-positive cells, which are characteristic of osteoclasts. Transcriptome and immunoblot analyses uncovered that TMBIM6 exerts its inhibitory effect on osteoclastogenesis by scavenging reactive oxygen species and preventing p65 nuclear localization. …

Short-Course Therapy For Urinary Tract Infections In Children: The Scout Randomized Clinical Trial, Theoklis Zaoutis, Nader Shaikh, Brian T Fisher, Susan E Coffin, Sonika Bhatnagar, Jeffrey S Gerber, Judith M Martin, Gysella B Muniz, Michael Green, Jennifer P Nagg, Sage R Myers, Rakesh D Mistry, Shawn O'Connor, Walter Faig, Stephen Black, Elizabeth Rowley, Kellie Liston, Alejandro Hoberman

Faculty, Staff and Student Publications

IMPORTANCE: There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI).

OBJECTIVE: To compare the efficacy of standard-course and short-course therapy for children with UTI.

DESIGN, SETTING, PARTICIPANTS: The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials.

INTERVENTION: Another …

Barriers And Facilitators To Home Dialysis Among Latinx Patients With Kidney Disease, Claudia Camacho

Faculty, Staff and Student Publications

Importance: Latinx people have a high burden of kidney disease but are less likely to receive home dialysis compared to non-Latinx White people. The disparity in home dialysis therapy has not been completely explained by demographic, medical, or social factors.

Objective: To understand the barriers and facilitators to home dialysis therapy experienced by Latinx individuals with kidney failure receiving home dialysis.

Design, setting, and participants: This qualitative study used semistructured interviews with Latinx adults with kidney failure receiving home dialysis therapy in Denver, Colorado, and Houston, Texas, between November 2021 and March 2023. Patients were recruited from home dialysis clinics …

Interpersonal Stress And Proinflammatory Activity In Emerging Adults With A History Of Suicide Risk: A Pilot Study, Emma D Whitmyre

Faculty, Staff and Student Publications

Interpersonal stress during adolescence and young adulthood can threaten healthy developmental trajectories. A “primed” proinflammatory response to acute stress may serve as an underlying process that results in negative outcomes for youth. The present pilot study examined the relation between interpersonal stress and two proinflammatory cytokines in a sample of 42 university-recruited emerging adults with recent suicidal thoughts and behaviors. Participants completed self-report measures of mood, suicidal thoughts and behaviors, recent peer-related stressors, and interpersonal sensitivity. They also participated in an acute laboratory social stress task and provided three saliva samples to measure their proinflammatory responses (IL-6 and TNF-α) to …

A Spatiotemporal Notch Interaction Map From Plasma Membrane To Nucleus, Alexandre P Martin, Gary A Bradshaw, Robyn J Eisert, Emily D Egan, Lena Tveriakhina, Andrew N Dates, Jon C Aster, Tom Kirchhausen, Marian Kalocsay, Stephen C Blacklow

Faculty, Staff and Student Publications

Notch signaling relies on ligand-induced proteolysis of the transmembrane receptor Notch to liberate a nuclear effector that drives cell fate decisions. Upon ligand binding, sequential cleavage of Notch by the transmembrane protease ADAM10 and the intracellular protease γ-secretase releases the Notch intracellular domain (NICD), which translocates to the nucleus and forms a complex that induces target gene transcription. To map the location and timing of the individual steps required for the proteolysis and movement of Notch from the plasma membrane to the nucleus, we used proximity labeling with quantitative, multiplexed mass spectrometry to monitor the interaction partners of endogenous NOTCH2 …

Fibroblast-Derived Pi16 Sustains Inflammatory Pain Via Regulation Of Cd206+ Myeloid Cells, Rachelle Garrity, Neha Arora, Md Areeful Haque, Drew Weis, Ronnie T Trinh, Susmita Kumari, Eroboghene E Ubogu, Rajasekaran Mahalingam, Diana Tavares-Ferreira, Theodore J Price, Annemieke Kavelaars, Cobi J Heijnen, Andrew J Shepherd

Faculty, Staff and Student Publications

Originally identified in fibroblasts, Protease Inhibitor (PI)16 was recently shown to be crucial for the development of neuropathic pain via effects on blood-nerve barrier permeability and leukocyte infiltration, though its impact on inflammatory pain has not been established. Using the complete Freund’s Adjuvant inflammatory pain model, we show that Pi16-/- mice are protected against sustained inflammatory pain. Accordingly, intrathecal delivery of a PI16 neutralizing antibody in wild-type mice prevented sustained CFA pain. In contrast to neuropathic pain models, we did not observe any changes in blood-nerve barrier permeability due to PI16 deletion. Instead, Pi16-/- mice display reduced macrophage density …

Barriers And Determinants Of Consistent Offering Of Hpv Vaccination By Healthcare Facilities, Ikponmwosa Osaghae, Onyema Greg Chido-Amajuoyi, Banda A A Khalifa, Sanjay Shete

Faculty, Staff and Student Publications

Expanding access to HPV vaccination is critical to increasing HPV vaccine uptake. We assessed the determinants and barriers to consistent offering of HPV vaccine among healthcare facilities. This was a cross-sectional survey of healthcare providers (HCPs) in Texas. Prevalence of the reasons healthcare practices do not consistently offer HPV vaccination was estimated. Multivariable regression analyses were conducted. Of 1169 HCPs included in the study, 47.5% (95% CI: 44.6-50.3%) reported their practices do not provide HPV vaccination or do not offer it consistently. Compared to physicians, nurses had 77% lower odds (Adjusted Odds Ratio (AOR): 0.23, 95% CI: 0.16-0.32, p-value: < .001), and physician assistants had 89% lower odds (AOR: 0.11, 95% CI: 0.07-0.16, p-value: < .001) of their healthcare practices consistently offering HPV vaccination. Compared to university/teaching hospitals, the odds of healthcare practices consistently offering HPV vaccination were 44% lower (AOR: 0.56, 95% CI: 0.35-0.91, p-value: 0.019) in solo practices but 266% higher (AOR: 3.66, 95% CI: 2.04-6.58, p-value: < .001) in FQHC/public facilities. The common reasons healthcare practices do not consistently offer HPV vaccination were; HPV vaccination is not within the scope of the practice (48.1%), referrals to other clinics (27.7%), and limited personnel (11.4%). Non-physicians were more likely to report that HPV vaccination was not in their scope and to refer patients than physicians. Moreover, solo practices were more likely to report challenges with acquisition and storage of the vaccine and referral of patients as reasons for not consistently offering HPV vaccination than university/teaching hospitals, FQHC/public facilities, or group practices. System-level interventions including training of non-physicians and expansion of practice enrollment in programs that support HPV vaccine acquisition and storage are needed.

Cardiac Substructure Radiation Dose And Risk Of Late Cardiac Disease In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, James E Bates, Suman Shrestha, Qi Liu, Susan A Smith, Daniel A Mulrooney, Todd Gibson, Eric J Chow, Kevin C Oeffinger, Gregory T Armstrong, Louis S Constine, Bradford S Hoppe, Choonsik Lee, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

PURPOSE: Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.

METHODS: Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.

RESULTS: The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 …

Pitfalls In Machine Learning-Based Assessment Of Tumor-Infiltrating Lymphocytes In Breast Cancer: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Jeppe Thagaard, Glenn Broeckx, David B Page, Chowdhury Arif Jahangir, Sara Verbandt, Rajarsi Gupta, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Guray Akturk, Jonas S Almeida, Isabel Alvarado-Cabrero, Mohamed Amgad, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Eva Balslev, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Najat Bouchmaa, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Anders B Dahl, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Johan Doré Hansen, Sarah N Dudgeon, Thomas Ebstrup, Mahmoud Elghazawy, Claudio Fernandez-Martín, Stephen B Fox, William M Gallagher, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Søren Hauberg, Stephen Hewitt, Akira I Hida, Hugo M Horlings, Zaheed Husain, Evangelos Hytopoulos, Sheeba Irshad, Emiel Am Janssen, Mohamed Kahila, Tatsuki R Kataoka, Kosuke Kawaguchi, Durga Kharidehal, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Amy Ly, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Arman Rahman, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Jorge S Reis-Filho, Joana M Ribeiro, David Rimm, Anne Roslind, Anne Vincent-Salomon, Manuel Salto-Tellez, Joel Saltz, Shahin Sayed, Ely Scott, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Susan Fineberg, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Paul J Van Diest, Gregory E Verghese, Giuseppe Viale, Michael Vieth, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, Reena Md Zin, Sylvia Adams, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Roberto Salgado, Elisabeth Specht Stovgaard

Faculty, Staff and Student Publications

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. …

Combining Voltage-Sensitive Dye, Carbon Fiber Array, And Extracellular Nerve Electrodes Using A 3-D Printed Recording Chamber And Manipulators, Curtis L Neveu, Yu Huan, Yuto Momohara, Paras R Patel, Hillel J Chiel, John H Byrne

Faculty, Staff and Student Publications

BACKGROUND: The analyses of neuronal circuits require high-throughput technologies for stimulating and recording many neurons simultaneously with single-neuron precision. Voltage-sensitive dyes (VSDs) have enabled the monitoring of membrane potentials of many (10-100 s) neurons simultaneously. Carbon fiber electrode (CFE) arrays allow for stimulation and recording of many neurons simultaneously, including intracellularly.

NEW METHOD: Combining CFE with VSD leverages the advantages of both technologies, allowing for stimulation of single neurons while recording the activity of the entire network. 3-D printing technology was used to develop a chamber to simultaneously perform VSD imaging, CFE array recording, and extracellular recording from individual glass …

Naltrexone Plus Bupropion Reduces Cigarette Smoking In Individuals With Methamphetamine Use Disorder: A Secondary Analysis From The Ctn Adapt-2 Trial, Yolanda R Villarreal, Steven Shoptaw, Madhukar H Trivedi

Faculty, Staff and Student Publications

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial.

Methods: The multi-site ADAPT-2 study used a randomized, …

Do Clinical Trials Prepare To Fail By Failing To Prepare? An Examination Of Ms Trials And Recommendations For Patient-Reported Outcome Measure Selection, Jeremy Hobart, Tanuja Chitnis, Jiwon Oh, Laurie Burke, Miriam King, Pamela Vo, Jo Vandercappellen, Andrew Lloyd

Peninsula Medical School

Background: Many clinical trials use patient-reported outcome (PRO) measures, which can influence treatmentdecision-making, drug approval and label claims. Given that many PRO measure options exist, and there areconceptual and contextual complexities with PRO measurement, we aimed to evaluate how and why specificPRO measures have been selected for pivotal multiple sclerosis (MS) clinical trials. Specifically, we aimed toidentify the reasons documented for PRO measure selection in contemporary phase III MS disease-modifyingtreatment (DMT) clinical trials.Methods: We searched for phase III clinical trials of MS DMTs published between 2015 and 2021 and evaluatedtrial protocols, or primary publications where available, for PRO measure selection …

Encephalitis In Hiv-Infected Adults In The Antiretroviral Therapy Era, Rodrigo Hasbun

Faculty, Staff and Student Publications

Introduction: Encephalitis presents with high morbidity and mortality in both HIV-infected and HIV-negative patients. There are currently no studies comparing HIV-infected and HIV-negative patients admitted to the hospital with acute encephalitis.

Methods: We conducted a multicenter, retrospective study of adults admitted to the hospital with a diagnosis of encephalitis in Houston, Texas between 2005 and 2020. We describe the clinical manifestations, etiology, and outcomes of these patients with a focus on those infected with HIV.

Results: We identified 260 patients with encephalitis, 40 of whom were infected with HIV. Viral etiology was identified in 18 of the 40 HIV-infected patients …

How Reclassification Of Hydrocodone Combination Products Affects Dispensing, Jonah J Stulberg, Lan Vu, Reiping Huang, Salva N Balbale, Phillip Yoo, Phiyen Tra, Leanne N Metcalfe

Faculty, Staff and Student Publications

No abstract provided.

Sources Of Calcium At Connexin 36 Gap Junctions In The Retina, Yuan-Hao Lee, W Wade Kothmann, Ya-Ping Lin, Alice Z Chuang, Jeffrey S Diamond, John O'Brien

Faculty, Staff and Student Publications

Synaptic plasticity is a fundamental feature of the CNS that controls the magnitude of signal transmission between communicating cells. Many electrical synapses exhibit substantial plasticity that modulates the degree of coupling within groups of neurons, alters the fidelity of signal transmission, or even reconfigures functional circuits. In several known examples, such plasticity depends on calcium and is associated with neuronal activity. Calcium-driven signaling is known to promote potentiation of electrical synapses in fish Mauthner cells, mammalian retinal AII amacrine cells, and inferior olive neurons, and to promote depression in thalamic reticular neurons. To measure local calcium dynamics in situ, …

Organizational Risk Profiling And Education Associated With Reduction In Professional Pitching Arm Injuries: A Natural Experiment, Garrett S Bullock, Charles A Thigpen, Gary S Collins, Nigel K Arden, Thomas J Noonan, Michael J Kissenberth, Douglas J Wyland, Ellen Shanley

Faculty, Staff and Student Publications

Background: Risk profiling and education are strategies implemented to help reduce injury risk; however, currently. there is little evidence on the effect of these interventions on injury incidence. The purpose of this study was to evaluate the influence of risk profiling and education on upper extremity injury incidence in minor league (MiLB) pitchers and to stratify by injury severity.

Methods: A prospective natural experiment study was conducted from 2013 to 2019 on MiLB pitchers. Beginning in the 2015 season, pitchers were examined and risk profiled for upper extremity injury. Shoulder external, internal, total range of motion, horizontal adduction, and humeral …

Primary Balloon Angioplasty Of Venous Sinus Stenosis In Idiopathic Intracranial Hypertension, Rosa Tang, Allison C Engstrom, Sunil Sheth, Claudia Pedroza, Arthur L Day, Peng Roc Chen

Faculty, Staff and Student Publications

Background: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH.

Methods: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), …

Biologic Versus Synthetic Mesh In Ventral Hernia Repair: Participant-Level Analysis Of Two Randomized Controlled Trials At Twenty-Four To Thirty-Six Months, Frank Primus

Faculty, Staff and Student Publications

Background: Biologic mesh has been used increasingly in complex ventral hernia repair despite limited evidence at low risk of bias supporting its use. Patients and

Methods: We performed a participant-level analysis of published randomized controlled trials (RCTs) comparing biologic to synthetic mesh with complex ventral hernia repair at 24 to 36 months. Primary outcome was major complication (composite of mesh infection, recurrence, reoperation, or death) at 24 to 36 months post-operative. Secondary outcomes included length of index hospital stay, surgical site occurrence, surgical site infection, and death. Outcomes were assessed using both frequentist and Bayesian generalized linear regression models.

Results: …

Eosinophils Promote Effector Functions Of Lung Group 2 Innate Lymphoid Cells In Allergic Airway Inflammation In Mice, Alfred D Doyle, Hirohito Kita, Elizabeth A Jacobsen

Faculty, Staff and Student Publications

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.

OBJECTIVE: We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.

METHODS: Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of …

Postoperative Respiratory Complications In Sars-Cov-2 Positive Pediatric Patients Across 20 United States Hospitals: A Cohort Study, Madelyn Hill, Kristen Born, Shale Mack, Abdulraouf Lamoshi, Aaron M Lipskar, Xiao-Yue Han, Elizabeth Fialkowski, Brianna Spencer, Afif N Kulaylat, Amrene Barde, Ami N Shah, Maeva Adoumie, Erica Gross, Steven C Mehl, Monica E Lopez, Valerie Polcz, Moiz M Mustafa, Jeffrey W Gander, Travis M Sullivan, Jason P Sulkowski, Owais Ghani, Eunice Y Huang, David Rothstein, E Peter Muenks, Shawn D St Peter, Jason C Fisher, Dina Levy-Lambert, Allison Reichl, Romeo C Ignacio, Bethany J Slater, Kuojen Tsao, Loren Berman

Faculty, Staff and Student Publications

INTRODUCTION: Data examining rates of postoperative complications among SARS-CoV-2 positive children are limited. The purpose of this study was to evaluate the impact of symptomatic and asymptomatic SARS-CoV-2 positive status on postoperative respiratory outcomes for children.

METHODS: This retrospective cohort study included SARS-CoV-2 positive pediatric patients across 20 hospitals who underwent general anesthesia from March to October 2020. The primary outcome was frequency of postoperative respiratory complications, including: high-flow nasal cannula/non invasive ventilation, reintubation, pneumonia, Extracorporeal Membrane Oxygenation (ECMO), and 30-day respiratory-related readmissions or emergency department (ED) visits. Univariate analyses were used to evaluate associations between patient and procedure characteristics …

Outcomes Of Induction Vs Prelabor Cesarean Delivery At <33 Weeks For Hypertensive Disorders Of Pregnancy, Ronald J Wapner, Mona Prasad, George R Saade, Yoram Sorokin, Dwight J Rouse, Sean C Blackwell, Jorge E Tolosa

Faculty, Staff and Student Publications

BACKGROUND: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain.

OBJECTIVE: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 >weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor.

STUDY DESIGN: This is a secondary analysis of an observational study which included 115,502 patients in 25 …