Medical Specialties Commons^™

Large-Scale Investigation Of White Matter Structural Differences In Bilingual And Monolingual Children: An Adolescent Brain Cognitive Development Data Study, Juliana Ronderos, Jennifer Zuk, Arturo E Hernandez, Kelly A Vaughn

Faculty, Staff and Student Publications

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive …

Genomic Staging Of Multifocal Lung Squamous Cell Carcinomas Is Independent Of The Comprehensive Morphologic Assessment, Sanja Dacic, Xuanye Cao, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, Sabina Berezowska, Yuchen Han, Jin-Haeng Chung, Mary Beth Beasley, Lin Dongmei, David Hwang, Mari Mino-Kenudson, Yuko Minami, Mauro Papotti, Natasha Rekhtman, Anja C Roden, Erik Thunnissen, Ming-Sound Tsao, Yasushi Yatabe, Akihiko Yoshida, Linghua Wang, Douglas J Hartman, Jacob A Jerome, Humam Kadara, Teh-Ying Chou, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.

Methods: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of …

Association Of Socioeconomic Factors And Severity Of Bronchiolitis Hospitalizations, Raymond Parlar-Chun, Zoabe Hafeez

Faculty, Staff and Student Publications

It is unclear if socioeconomic status (SES) factors influence severity of illness of patients hospitalized with bronchiolitis. This study was conducted to identify SES factors including the Center for Disease Control and Prevention’s Social Vulnerability Composite Index (SVI), estimated income, proportion of minority, proportion of living below poverty, insurance status, and number of household members associated with length of stay (LOS) and intensive care unit admission. Infants hospitalized at a tertiary care urban center for bronchiolitis were identified using International Classification of Diseases codes. Federal information processing system codes were identified from home address and paired with SVI and 2018 …

The Future Of Targeting Cytotoxic T-Lymphocyte-Associated Protein-4: Is There A Role?, Anna Maria Di Giacomo, Michael Lahn, Alexander Mm Eggermont, Bernard Fox, Ramy Ibrahim, Padmanee Sharma, James P Allison, Michele Maio

Faculty, Staff and Student Publications

The 2022 yearly Think Tank Meeting in Siena, Tuscany (Italy), organized by the Italian Network for Tumor Biotherapy (NIBIT) Foundation, the Parker Institute for Cancer Immunotherapy and the World Immunotherapy Council, included a focus on the future of integrating and expanding the use of targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The conference members exchanged their views on the lessons from targeting CTLA-4 and compared the effect to the impact of blocking Programmed cell death protein 1 (PD1) or its ligand (PDL1). The increasing experience with both therapeutic approaches and their combination suggests that targeting CTLA-4 may lead to more durable …

Experiences Of Patients With Peritoneal Carcinomatosis-Related Complex Care Needs And Their Caregivers, Rachel A Pozzar, Jaclyn A Wall, Anna Tavormina, Embree Thompson, Andrea C Enzinger, Ursula A Matulonis, Susana Campos, Larissa A Meyer, Alexi A Wright

Faculty, Staff and Student Publications

Background: Patients with peritoneal carcinomatosis (PC) frequently undergo palliative procedures, yet these patients and their caregivers report being unprepared to manage ostomies, drains, and other complex care needs at home. The purpose of this study was to characterize the unique needs of these patients and their caregivers during care transitions.

Methods: Patients completed measures of health status and advance care planning, caregivers completed measures of preparedness and burden, and all participants completed measures of depression and anxiety. Participants detailed their experiences in individual, semi-structured interviews. We analyzed data using descriptive statistics and conventional content analysis.

Results: Sixty-one patients and 39 …

Acquisition Of Tp63 Rearrangement In Large Cell Transformation Of Mycosis Fungoides, Karen A Nahmod, Guilin Tang, Shaoying Li, Carlos Torres-Cabala, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Sox11+ Large B-Cell Neoplasms: Cyclin D1-Negative Blastoid/Pleomorphic Mantle Cell Lymphoma Or Large B-Cell Lymphoma?, Shaoying Li, Guilin Tang, Preetesh Jain, Pei Lin, Jie Xu, Roberto N Miranda, Joanne Cheng, C Cameron Yin, M James You, Michael L Wang, L Jeffrey Medeiros

Faculty, Staff and Student Publications

Large or blastoid B-cell neoplasms that are SOX11+ are a diagnostic dilemma and raise a differential diagnosis of cyclin D1-negative blastoid/pleomorphic mantle cell lymphoma (MCL) versus diffuse large B-cell lymphoma (DLBCL) or blastoid high-grade B-cell lymphoma (HGBL) with aberrant SOX11 expression. Here we report a study cohort of 13 SOX11+ large/blastoid B-cell neoplasms. Fluorescence in situ hybridization analysis was negative for CCND1 rearrangement in all 13 cases; 1 of 8 (12.5%) cases tested showed CCND2 rearrangement and 2 (25%) cases had extracopies of CCND2. Gene expression profiling showed that the study group had a gene expression signature similar to cyclin …

Trigeminal Neuralgia As A Primary Demyelinating Disease: Potential Multimodal Evidence And Remaining Controversies, Seyed H Mousavi, John W Lindsey, Karin N Westlund, Sascha R A Alles

Faculty, Staff and Student Publications

Trigeminal neuralgia is a heterogeneous disorder with likely multifactorial and complex etiology; however, trigeminal nerve demyelination and injury are observed in almost all patients with trigeminal neuralgia. The current management strategies for trigeminal neuralgia primarily involve anticonvulsants and surgical interventions, neither of which directly address demyelination, the pathological hallmark of trigeminal neuralgia, and treatments targeting demyelination are not available. Demyelination of the trigeminal nerve has been historically considered a secondary effect of vascular compression, and as a result, trigeminal neuralgia is not recognized nor treated as a primary demyelinating disorder. In this article, we review the evolution of our understanding …

Characteristics And Outcomes Of Patients With Multiple Myeloma Who Developed Therapy-Related Acute Myeloid Leukemia And Myelodysplastic Syndrome After Autologous Cell Transplantation, Fevzi F Yalniz, Uri Greenbaum, Oren Pasvolsky, Denái R Milton, Rashmi Kanagal-Shamanna, Jeremy Ramdial, Samer Srour, Rohtesh Mehta, Amin Alousi, Uday R Popat, Yago Nieto, Partow Kebriaei, Gheath Al-Atrash, Betul Oran, Chitra Hosing, Sairah Ahmed, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Qaiser Bashir

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1 January and 31 December 2018 and later developed t-MDS/AML. Among the 2982 patients who underwent at least 1 Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n = 52; AML, n = 3). The median age at t-MDS/AML diagnosis was 66 years (range 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis …

Brain Endothelial Cd200 Signaling Protects Brain Against Ischemic Damage, Afzal Misrani, Conelius Ngwa, Abdullah Al Mamun, Romana Sharmeen, Kanaka Valli Manyam, Rodney M Ritzel, Louise Mccullough, Fudong Liu

Faculty, Staff and Student Publications

Ischemic stroke induced inflammatory responses contribute significantly to neuronal damage and stroke outcomes. CD200 ligand and its receptor, CD200R, constitute an endogenous inhibitory signaling that is being increasingly recognized in studies of neuroinflammation in various central nervous system disorders. CD200 is a type 1 membrane glycoprotein that is broadly expressed by endothelia and neurons in the brain. In the present study, we have examined the role of endothelial CD200 signaling in acute ischemic stroke. Endothelial CD200 conditional knock out (CKO) mice were generated by breeding CD200 gene floxed mice with Cdh5^Cre mice. The mice were subjected to a 60-min …

Circulating Tumor Dna And Radiological Tumor Volume Identify Patients At Risk For Relapse With Resected, Early-Stage Non-Small-Cell Lung Cancer, H T Tran, S Heeke, S Sujit, N Vokes, J Zhang, M Aminu, V K Lam, A Vaporciyan, S G Swisher, M C B Godoy, T Cascone, B Sepesi, D L Gibbons, J Wu, J V Heymach

Faculty, Staff and Student Publications

Background: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome.

Patients and methods: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation.

Results: Our results showed that patients with detectable ctDNA at baseline or after treatment and …

Dermatology Healthcare Utilization In Solid-Organ Transplant Recipients: A Retrospective Cohort Study, Carly F Stender, Lucy J Navsaria, Jiangong Niu, Nasim Khalfe, Candice L Hinkston, Sharon H Giordano, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation, Lauri Holmstrom, Bryan Bednarski, Harpriya Chugh, Habiba Aziz, Hoang Nhat Pham, Arayik Sargsyan, Audrey Uy-Evanado, Damini Dey, Angelo Salvucci, Jonathan Jui, Kyndaron Reinier, Piotr J Slomka, Sumeet S Chugh

Faculty, Staff and Student Publications

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor.

METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is …

The Role Of Palliative Care Consultation In Withdrawal Of Life-Sustaining Treatment Among Icu Patients Receiving Veno-Venous Extracorporeal Membrane Oxygenation (Vv-Ecmo): A Retrospective Case-Control Study, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

The Role Of Peroxisome Proliferator-Activated Receptors In The Development And Physiology Of Gametes And Preimplantation Embryos, Gabriel Patarroyo-Aponte, Saeed Shoar, Deptmer M Ashley, Ali Noorbaksh, Dev Patel, Alisha Y Young, Bindu H Akkanti, Mark T Warner, Maria M Patarroyo-Aponte, Biswajit Kar, Igor D Gregoric, Caroline Ha, Bela Patel

Faculty, Staff and Student Publications

Background: Extracorporeal membrane oxygenation (ECMO) has extended the survivability of critically ill patients beyond their unsupported prognosis and has widened the timeframe for making an informed decision about the goal of care. However, an extended time window for survival does not necessarily translate into a better outcome and the sustaining treatment is ultimately withdrawn in many patients. Emerging evidence has implicated the determining role of palliative care consult (PCC) in direction of the care that critically ill patients receive. Objective: To evaluate the impact of PCC in withdrawal of life-sustaining treatment (WOLST) among critically ill patients, who were placed on …

Antiviral Potency Of Long-Acting Islatravir Subdermal Implant In Shiv-Infected Macaques, Fernanda P Pons-Faudoa, Nicola Di Trani, Simone Capuani, Ilaria Facchi, Anthony M Wood, Bharti Nehete, Ashley Delise, Suman Sharma, Kathryn A Shelton, Lane R Bushman, Corrine Ying Xuan Chua, Michael M Ittmann, Jason T Kimata, Peter L Anderson, Pramod N Nehete, Roberto C Arduino, Alessandro Grattoni

Faculty, Staff and Student Publications

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded …

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Faculty, Staff and Student Publications

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

Endolysosomal Trafficking Controls Yolk Granule Biogenesis In Vitellogenic Drosophila Oocytes, Yue Yu, Dongsheng Chen, Stephen M Farmer, Shiyu Xu, Beatriz Rios, Amanda Solbach, Xin Ye, Lili Ye, Sheng Zhang

Faculty, Staff and Student Publications

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage …

Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang

Faculty, Staff and Student Publications

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) …

Enhancing Anti-Aml Activity Of Venetoclax By Isoflavone Me-344 Through Suppression Of Oxphos And/Or Purine Biosynthesis In Vitro, Katie H Hurrish, Yongwei Su, Shraddha Patel, Cassandra L Ramage, Jianlei Zhao, Brianna R Temby, Jenna L Carter, Holly Edwards, Steven A Buck, Sandra E Wiley, Maik Hüttemann, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Xun Bao, Jing Li, Jay Yang, Julie Boerner, Zhanjun Hou, Gheath Al-Atrash, Sergej N Konoplev, Jonathan Busquets, Stefano Tiziani, Larry H Matherly, Jeffrey W Taub, Marina Konopleva, Yubin Ge, Natalia Baran

Faculty, Staff and Student Publications

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that …

Lfsproshiny: An Interactive R/Shiny App For Prediction And Visualization Of Cancer Risks In Families With Deleterious Germline Tp53 Mutations, Nam H Nguyen, Elissa B Dodd-Eaton, Gang Peng, Jessica L Corredor, Wenwei Jiao, Jacynda Woodman-Ross, Banu K Arun, Wenyi Wang

Faculty, Staff and Student Publications

Purpose: LFSPRO is an R library that implements risk prediction models for Li-Fraumeni syndrome (LFS), a genetic disorder characterized by deleterious germline mutations in the TP53 gene. To facilitate the use of these models in clinics, we developed LFSPROShiny, an interactive R/Shiny interface of LFSPRO that allows genetic counselors (GCs) to perform risk predictions without any programming components and further visualize the risk profiles of their patients to aid the decision-making process.

Methods: LFSPROShiny implements two models that have been validated on multiple LFS patient cohorts: a competing risk model that predicts cancer-specific risks for the first primary and a …

What's Going Well: A Qualitative Analysis Of Positive Patient And Family Feedback In The Context Of The Diagnostic Process, Stephen K Liu, Fabienne Bourgeois, Joe Dong, Kendall Harcourt, Elizabeth Lowe, Liz Salmi, Eric J Thomas, Natalie Riblet, Sigall K Bell

Faculty, Staff and Student Publications

OBJECTIVES: Accurate and timely diagnosis relies on close collaboration between patients/families and clinicians. Just as patients have unique insights into diagnostic breakdowns, positive patient feedback may also generate broader perspectives on what constitutes a "good" diagnostic process (DxP).

METHODS: We evaluated patient/family feedback on "what's going well" as part of an online pre-visit survey designed to engage patients/families in the DxP. Patients/families living with chronic conditions with visits in three urban pediatric subspecialty clinics (site 1) and one rural adult primary care clinic (site 2) were invited to complete the survey between December 2020 and March 2022. We adapted the …

A Novel Multimodal Approach To Refractory Brain Metastases: A Case Report, Kalman A Katlowitz, Thomas H Beckham, Rajat J Kudchadker, Jeffrey Wefel, Yasir Y Elamin, Jeffrey S Weinberg

Faculty, Staff and Student Publications

No abstract provided.

Gli1-Altered Mesenchymal Tumors With Actb Or Ptch1 Fusion: A Molecular And Clinicopathologic Analysis, Darcy A Kerr, Jeffrey M Cloutier, Matthew Margolis, Douglas A Mata, Nathalie J Rodrigues Simoes, William C Faquin, Dora Dias-Santagata, Shefali Chopra, Gregory W Charville, Sintawat Wangsiricharoen, Alexander J Lazar, Wei-Lien Wang, Andrew E Rosenberg, Julie Y Tse

Faculty, Staff and Student Publications

Mesenchymal tumors with GLI1 fusions or amplifications have recently emerged as a distinctive group of neoplasms. The terms GLI1-altered mesenchymal tumor or GLI1-altered soft tissue tumor serve as a nosological category, although the exact boundaries/criteria require further elucidation. We examined 16 tumors affecting predominantly adults (median age: 40 years), without sex predilection. Several patients had tumors of longstanding duration (>10 years). The most common primary site was soft tissue (n = 9); other sites included epidural tissue (n = 1), vertebra (n = 1), tongue (n = 1), hard palate (n = 1), and liver (n = 1). Histologically, …

Vitamin D Oral Replacement In Children With Obesity Related Asthma: Vdora1 Randomized Clinical Trial., Brian O'Sullivan, Song Ounpraseuth, Laura James, Marc Majure, Jason Lang, Zhuopei Hu, Alan Simon, Scott Bickel, Brian Ely, L E Faricy, Maryam Garza, Melody Greer, Daniel Hsia, Akilah Jefferson, Lisa Knight, Jeannette Lee, Deborah Liptzin, Mehtap Haktanir Abul, Tamara T. Perry, Fred Prior, Christine Sangiovanni, Jade B. Tam-Williams, Brian Wu, Jessica Snowden, Echo Idea States Pediatric Clinical Trial Network

Manuscripts, Articles, Book Chapters and Other Papers

Children with asthma and obesity are more likely to have lower vitamin D levels, but the optimal replacement dose is unknown in this population. The objective of this study is identifying a vitamin D dose in children with obesity-related asthma that safely achieves serum vitamin D levels of ≥ 40 ng/mL. This prospective multisite randomized controlled trial recruited children/adolescents with asthma and body mass index ≥ 85% for age/sex. Part 1 (dose finding), evaluated 4 oral vitamin D regimens for 16 weeks to identify a replacement dose that achieved serum vitamin D levels ≥ 40 ng/mL. Part 2 compared the …

Nci10066: A Phase 1/2 Study Of Olaparib In Combination With Ramucirumab In Previously Treated Metastatic Gastric And Gastroesophageal Junction Adenocarcinoma, Michael Cecchini, James M Cleary, Yu Shyr, Joseph Chao, Nataliya Uboha, May Cho, Anthony Shields, Shubham Pant, Laura Goff, Kristen Spencer, Edward Kim, Stacey Stein, Jeremy S Kortmansky, Sandra Canosa, Jeffrey Sklar, Elizabeth M Swisher, Marc Radke, Percy Ivy, Scott Boerner, Diane E Durecki, Chih-Yuan Hsu, Patricia Lorusso, Jill Lacy

Faculty, Staff and Student Publications

Background: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.

Patients and methods: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR).

Results: Fifty-one patients …

Knowledge And Attitudes On Contraception And Reproductive Health In Women With Hiv, Anna Henricks, Samantha Singal, Dana Hughes, Sean Kelly, Jessica L Castilho, Jamison Norwood

Faculty, Staff and Student Publications

BACKGROUND: For reasons not fully explained to date, contraception usage among women with HIV remains low. The aim of our study was to understand attitudes toward and lifetime use of contraception among women with HIV.

METHODS: We administered an anonymous, community-informed, voluntary survey to cisgender, English-speaking women with HIV (≥18 years of age) at a Southern urban HIV clinic. It included multiple choice and Likert-scale questions on reproductive health. Participants reported contraception use, recollection of provider conversations about contraception, and perceived empowerment and knowledge regarding reproductive health. We used chi-square and Fisher exact tests to compare attitudes and prior conversations …

Age-Associated Disparity In Phagocytic Clearance Affects The Efficacy Of Cancer Nanotherapeutics, Yifan Wang, Weiye Deng, Daeyong Lee, Long Yan, Yifei Lu, Shiyan Dong, Kristin Huntoon, Abin Antony, Xuefeng Li, Rui Ye, Yan Zhao, Feiyan Zhao, Benjamin R Schrank, Jonghoon Ha, Minjeong Kang, Mingming Yang, Ping Gong, Philip L Lorenzi, Lin Tan, Thomas D Gallup, Sarah K Tang, Zhaogang Yang, Jing Li, Nina N Sanford, Hongmei Wang, Betty Y S Kim, Wen Jiang

Faculty, Staff and Student Publications

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity. Tumour delivery and treatment outcomes are superior in old versus young mice, probably due to an age-related decline in the ability of hepatic phagocytes to take up and remove nanoparticles. Transcriptomic- and protein-level analysis at the single-cell and bulk levels reveals an age-associated decrease in the numbers of hepatic macrophages that express the scavenger …

The Influence Of Incubation Temperature On Offspring Traits Varies Across Northern And Southern Populations Of The American Alligator (Alligator Mississippiensis), Christopher R Smaga, Samantha L Bock, Josiah M Johnson, Thomas Rainwater, Randeep Singh, Vincent Deem, Andrew Letter, Arnold Brunell, Benjamin B Parrott

Faculty, Staff and Student Publications

Maternal provisioning and the developmental environment are fundamental determinants of offspring traits, particularly in oviparous species. However, the extent to which embryonic responses to these factors differ across populations to drive phenotypic variation is not well understood. Here, we examine the contributions of maternal provisioning and incubation temperature to hatchling morphological and metabolic traits across four populations of the American alligator (Alligator mississippiensis), encompassing a large portion of the species' latitudinal range. Our results show that whereas the influence of egg mass is generally consistent across populations, responses to incubation temperature show population-level variation in several traits, including …