Medicine and Health Sciences Commons^™

Sctiger: A Deep-Learning Method For Inferring Gene Regulatory Networks From Case Versus Control Scrna-Seq Datasets., Madison Dautle, Shaoqiang Zhang, Yong Chen

College of Science & Mathematics Departmental Research

Inferring gene regulatory networks (GRNs) from single-cell RNA-seq (scRNA-seq) data is an important computational question to find regulatory mechanisms involved in fundamental cellular processes. Although many computational methods have been designed to predict GRNs from scRNA-seq data, they usually have high false positive rates and none infer GRNs by directly using the paired datasets of case-versus-control experiments. Here we present a novel deep-learning-based method, named scTIGER, for GRN detection by using the co-differential relationships of gene expression profiles in paired scRNA-seq datasets. scTIGER employs cell-type-based pseudotiming, an attention-based convolutional neural network method and permutation-based significance testing for inferring GRNs among …

Perspectives On Long-Acting Formulations Of Pre-Exposure Prophylaxis (Prep) Among Men Who Have Sex With Men Who Are Non-Adherent To Daily Oral Prep In The United States, Brooke G Rogers, R R Patel, K Curoe, J Villalobos, A Underwood, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP.

METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis.

RESULTS: Participants …

Microglial Rev-Erbα Regulates Inflammation And Lipid Droplet Formation To Drive Tauopathy In Male Mice, Jiyeon Lee, Julie M Dimitry, Jong Hee Song, Minsoo Son, Patrick W Sheehan, Melvin W King, G Travis Tabor, Young Ah Goo, Mitchell A Lazar, Leonard Petrucelli, Erik S Musiek

2020-Current year OA Pubs

Alzheimer's disease, the most common age-related neurodegenerative disease, is characterized by tau aggregation and associated with disrupted circadian rhythms and dampened clock gene expression. REV-ERBα is a core circadian clock protein which also serves as a nuclear receptor and transcriptional repressor involved in lipid metabolism and macrophage function. Global REV-ERBα deletion has been shown to promote microglial activation and mitigate amyloid plaque formation. However, the cell-autonomous effects of microglial REV-ERBα in healthy brain and in tauopathy are unexplored. Here, we show that microglial REV-ERBα deletion enhances inflammatory signaling, disrupts lipid metabolism, and causes lipid droplet (LD) accumulation specifically in male …

Bioaccumulation Of Non-Essential Trace Elements Detected In Women's Follicular Fluid, Urine, And Plasma Is Associated With Poor Reproductive Outcomes Following Single Euploid Embryo Transfer: A Pilot Study, Andrea Palomar, Roberto Gonzalez-Martin, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Isabel Rucandio, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Caroline Zuckerman, Christine Whitehead, Richard T. Scott, Francisco Dominguez

Department of Obstetrics and Gynecology Faculty Papers

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of …

Effect Of Various Types Of Extracellular Dna On V Hyugaensis Biofilm Formation, Carmen Gu Liu, Anthony W Maresso

Faculty, Staff and Students Publications

Marine bacteria face a constant influx of new extracellular DNA (exDNA) due to the massive viral lysis that occurs in the ocean on a daily basis. Generally, biofilms have shown to be induced by self-secreted exDNA. However, the effect of various types of exDNA with varying lengths, self vs non-self, as well as guanine-cytosine content (GC) content on biofilm formation has not been explored, despite being a critical component of the extracellular polymeric substance. To test the effect of such exDNA on biofilms, a marine bioluminescent bacterium (Vibrio hyugaensis) was isolated from the Sippewissett Salt Marsh, USA, and …

Identification Of Usp9x As A Leukemia Susceptibility Gene, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Sejal Salvi, Harsha Doddapaneni, Donna Muzny, Danielle Mitchell, Olga Taylor, Aniko Sabo, Philip J Lupo, Sharon E Plon

Faculty, Staff and Students Publications

We recently reported that children with multiple birth defects have a significantly higher risk of childhood cancer. We performed whole-genome sequencing on a cohort of probands from this study with birth defects and cancer and their parents. Structural variant analysis identified a novel 5 kb de novo heterozygous inframe deletion overlapping the catalytic domain of USP9X in a female proband with multiple birth defects, developmental delay, and B-cell acute lymphoblastic leukemia (B-ALL). Her phenotype was consistent with female-restricted X-linked syndromic intellectual developmental disorder-99 (MRXS99F). Genotype-phenotype analysis including previously reported female probands (n = 42) demonstrated that MRXS99F probands with B-ALL …

Identifying The Reactive Metabolites Of Tyrosine Kinase Inhibitor Pexidartinib In Vitro Using Lc-Ms-Based Metabolomic Approaches, Xuan Qin, Yong Wang, Kevin R Mackenzie, John M Hakenjos, Si Chen, Saleh M Khalil, Sung Yun Jung, Damian W Young, Lei Guo, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO), a selective and potent inhibitor of the macrophage colony-stimulating factor-1 receptor, has been approved for the treatment of tenosynovial giant cell tumor. However, frequent and severe adverse effects have been reported in the clinic, resulting in a boxed warning on PEX for its risk of liver injury. The mechanisms underlying PEX-related hepatotoxicity, particularly metabolism-related toxicity, remain unknown. In the current study, the metabolic activation of PEX was investigated in human/mouse liver microsomes (HLM/MLM) and primary human hepatocytes (PHH) using glutathione (GSH) and methoxyamine (NH2OMe) as trapping reagents. A total of 11 PEX-GSH and 7 PEX-NH2OMe adducts were …

Detection Method Has Independent Prognostic Significance In The Plco Lung Screening Trial, James P Long, Yu Shen

Faculty, Staff and Student Publications

Prognostic models in cancer use patient demographic and tumor characteristics to predict survival and dynamic disease prognosis. Past work in breast cancer has shown that cancer detection method, screen-detected or symptom-detected, has prognostic significance. We investigate this phenomenon in the lung component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. Patients were randomized to intervention, receiving four annual chest x-rays (CXRs), or to control, receiving usual care. Patients were followed for a total of approximately 13 years. In PLCO, lung cancer detection method has independent prognostic value exceeding that of variables commonly used in lung cancer prognostic models, …

Home-Based Self-Sampling Vs Clinician Sampling For Anal Precancer Screening: The Prevent Anal Cancer Self-Swab Study, Alan G Nyitray, Jenna Nitkowski, Timothy L Mcauliffe, Bridgett Brzezinski, Michael D Swartz, María E Fernandez, Ashish A Deshmukh, Timothy J Ridolfi, Sarah J Lundeen, Leslie Cockerham, Dave Wenten, Andrew Petroll, Brian Hilgeman, Jennifer S Smith, Elizabeth Y Chiao, Anna R Giuliano, Vanessa Schick, Prevent Anal Cancer Self-Swab Study Team

Faculty, Staff and Student Publications

Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV …

Atypical Intraparenchymal Meningioma With Yap1-Maml2 Fusion In A Young Adult Male: A Case Report And Mini Literature Review., Alisa Nobee, Mei Xu, Anjali Seth, Yuan Rong

PCOM Scholarly Works

Oncogenic Yes-associated protein (YAP) 1 fusions have been recently identified in several cases of meningioma mostly involving pediatric patients. The meningiomas harboring YAP1-MAML2, which is the most frequent fusion subtype, exhibit activated YAP1 signaling and share similarities with NF2 (neurofibromatosis type 2 gene) mutant meningiomas. We reported a rare case of atypical intraparenchymal meningioma with YAP1-MAML2 fusion in a 20-year-old male. The patient presented with an episode of seizure without a medical history. MRI revealed a lesion in the right temporal lobe without extra-axial involvement. The radiological and morphological findings, however, were indistinctive from other intracranial diseases, e.g., vascular malformation …

Loss Of Syncrip Unleashes Apobec-Driven Mutagenesis, Tumor Heterogeneity, And Ar-Targeted Therapy Resistance In Prostate Cancer, Xiaoling Li, Yunguan Wang, Su Deng, Guanghui Zhu, Choushi Wang, Nickolas A Johnson, Zeda Zhang, Carla Rodriguez Tirado, Yaru Xu, Lauren A Metang, Julisa Gonzalez, Atreyi Mukherji, Jianfeng Ye, Yuqiu Yang, Wei Peng, Yitao Tang, Mia Hofstad, Zhiqun Xie, Heewon Yoon, Liping Chen, Xihui Liu, Sujun Chen, Hong Zhu, Douglas Strand, Han Liang, Ganesh Raj, Housheng Hansen He, Joshua T Mendell, Bo Li, Tao Wang, Ping Mu

Faculty, Staff and Student Publications

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, …

Generation Of A Novel Stra8-Driven Cre Recombinase Strain For Use In Pre-Meiotic Germ Cells In Mice†, Avery A Ahmed, Ernesto Salas, Denise G Lanza, Jason D Heaney, Stephanie A Pangas

Faculty, Staff and Students Publications

The development of oocytes occurs over a broad time frame, starting at the earliest stages of embryogenesis and continuing into adulthood. Conditional knockout technologies such as the Cre/loxP recombination system are useful for analyzing oocyte development at specific stages, but not every time frame has appropriate Cre drivers, for instance, during oocyte meiotic initiation through early prophase I in the embryo. Here, we generated a novel knockin mouse line that produces a bicistronic transcript from the endogenous Stra8 locus that includes a "self-cleaving" 2A peptide upstream of cre. This allows for high efficiency cleavage and production of both proteins individually …

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini

Faculty, Staff and Student Publications

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior …

Loss Of Microrna-30a And Sex-Specific Effects On The Neonatal Hyperoxic Lung Injury, Sandra L Grimm, Samuel Reddick, Xiaoyu Dong, Connor Leek, Amy Xiao Wang, Manuel Cantu Gutierrez, Sean M Hartig, Bhagavatula Moorthy, Cristian Coarfa, Krithika Lingappan

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.

METHODS: Wild-type and miR-30a−/− neonatal mice were exposed …

Influence Of Participant And Reviewer Characteristics In Application Scores For A Hematology Research Training Program, Sara K Vesely, Allison King, Emily Vettese, John G Heller, Adam Cuker, Cecelia Calhoun, Wendy Stock, Morgan Homer, Josel Fritz, Lillian Sung

2020-Current year OA Pubs

The American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. …

Combined Crispri And Proteomics Screening Reveal A Cohesin-Ctcf-Bound Allele Contributing To Increased Expression Of Ruvbl1 And Prostate Cancer Progression, Yijun Tian, Dandan Dong, Zixian Wang, Lang Wu, Jong Y Park, Gong-Hong Wei, Liang Wang

Faculty, Staff and Student Publications

Genome-wide association studies along with expression quantitative trait locus (eQTL) mapping have identified hundreds of single-nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PCa), yet functional characterization of these risk loci remains challenging. To screen for potential regulatory SNPs, we designed a CRISPRi library containing 9,133 guide RNAs (gRNAs) to cover 2,166 candidate SNP loci implicated in PCa and identified 117 SNPs that could regulate 90 genes for PCa cell growth advantage. Among these, rs60464856 was covered by multiple gRNAs significantly depleted in screening (FDR < 0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (p value = 1.2 × 10

Urachal Xanthogranuloma: A Rare But Important Case Presenting As A Urachal Mass, Kunal Jain, Esha Jain, Richard Dilena, Rola Saleeb, Umesh Jain

Faculty, Staff and Student Publications

BACKGROUND: A urachal mass is a relatively rare presentation to the urologists' practice, often requiring radical surgical excision for a definitive diagnosis. Xanthogranulomatous inflammation of the urachus is an extremely rare entity with few cases reported worldwide, and to the best of our knowledge, no cases reported in the western world.

CASE PRESENTATION: In this case, a 55-year-old male patient presented with bothersome lower urinary tract symptoms and computed tomography findings demonstrating a urachal mass that was worrisome for urachal carcinoma. Following surgical intervention, histopathology revealed urachal xanthogranuloma. Post-operatively, the patient recovered well, and eventually, he had symptomatic and radiologic …

Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas

Department of Jefferson Headache Center Papers and Presentations

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same …

Two Thymomas Of Different Histological Subtypes Arising In A Giant Thymolipoma: Case Report And Review Of The Literature., Vincent C Daniel, Konstantin Shilo

Surgery Articles

Thymolipoma is a rare benign tumor of the anterior mediastinum. Only a few reports describing thymoma arising within a thymolipoma have been documented in the literature. We report herein a detailed description of thymolipoma giving rise to 2 thymomas of different histological subtypes. A 74-year-old male with history of metastatic papillary thyroid carcinoma gradually developed 2 soft tissue nodules within a large right hemithorax fatty mass that was present for the past 20 years. Computed tomography (CT)-guided needle biopsy revealed one of the soft tissue nodules to be a thymoma, and the entire mass was surgically resected. Final pathological examination …

Major Cardiovascular Events After Covid-19, Event Rates Post-Vaccination, Antiviral Or Anti-Inflammatory Therapy, And Temporal Trends: Rationale And Methodology Of The Corona-Vte-Network Study, Behnood Bikdeli, Candrika D Khairani, Darsiya Krishnathasan, Antoine Bejjani, Andre Armero, Anthony Tristani, Julia Davies, Nicole Porio, Ali A Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Aditya Achanta, Sirus J Jesudasen, Bruce C Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya Sharma, Alec Vishnevsky, Judith Hsia, Mark R Nehler, James Welker, Marc P Bonaca, Brett J Carroll, Zhou Lan, Samuel Z Goldhaber, Gregory Piazza

Division of Cardiology Faculty Papers

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied.

METHODS: Adult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 …

Infants Admitted To Us Intensive Care Units For Rsv Infection During The 2022 Seasonal Peak., Natasha Halasa, Laura D. Zambrano, Justin Z. Amarin, Laura S. Stewart, Margaret M. Newhams, Emily R. Levy, Steven L. Shein, Christopher L. Carroll, Julie C. Fitzgerald, Marian G. Michaels, Katherine Bline, Melissa L. Cullimore, Laura Loftis, Vicki L. Montgomery, Asumthia S. Jeyapalan, Pia S. Pannaraj, Adam J. Schwarz, Natalie Z. Cvijanovich, Matt S. Zinter, Aline B. Maddux, Melania M. Bembea, Katherine Irby, Danielle M. Zerr, Joseph D. Kuebler, Christopher J. Babbitt, Mary Glas Gaspers, Ryan A. Nofziger, Michele Kong, Bria M. Coates, Jennifer E. Schuster, Shira J. Gertz, Elizabeth H. Mack, Benjamin R. White, Helen Harvey, Charlotte V. Hobbs, Heda Dapul, Andrew D. Butler, Tamara T. Bradford, Courtney M. Rowan, Kari Wellnitz, Mary Allen Staat, Cassyanne L. Aguiar, Saul R. Hymes, Adrienne G. Randolph, Angela P. Campbell, Rsv-Pic Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.

EXPOSURE: Respiratory syncytial virus.

MAIN OUTCOMES AND MEASURES: Data were captured on demographics, …

Alcohol Consumption Among Adults With A Cancer Diagnosis In The All Of Us Research Program, Mengyao Shi, Chongliang Luo, Oluseye K Oduyale, Xiaoyu Zong, Noelle K Loconte, Yin Cao

2020-Current year OA Pubs

IMPORTANCE: Alcohol consumption is associated with adverse oncologic and treatment outcomes among individuals with a diagnosis of cancer. As a key modifiable behavioral factor, alcohol consumption patterns among cancer survivors, especially during treatment, remain underexplored in the United States.

OBJECTIVE: To comprehensively characterize alcohol consumption patterns among US cancer survivors.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from May 6, 2018, to January 1, 2022, from the National Institutes of Health All of Us Research Program, a diverse US cohort with electronic health record (EHR) linkage, and included 15 199 participants who reported a cancer diagnosis and 1839 …

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A Schultz, Eric Mcdade, Nicolas R Barthelemy, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D Chen, Tammie L S Benzinger, Anne M Fagan, Brian A Gordon, Jason J Hassenstab, Celeste M Karch, John C Morris, Richard J Perrin, Chengjie Xiong, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Androgen Deprivation And Radiotherapy With Or Without Docetaxel For Localized High-Risk Prostate Cancer: Long-Term Follow-Up From The Randomized Nrg Oncology Rtog 0521 Trial, Oliver Sartor, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.

DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. …

Dengue Outbreak Response During Covid-19 Pandemic, Key Largo, Florida, Usa, 2020, Devin Rowe, Catherine Mcdermott, Ysla Veliz, Alison Kerr, Mark Whiteside, Mikki Coss, Chad Huff, Andrea Leal, Edgar Kopp, Alexis Lacrue, Lea A Heberlein, Laura E Adams, Gilberto A Santiago, Jorge L Munoz-Jordan, Gabriela Paz-Bailey, Andrea M Morrison

Faculty, Staff and Student Publications

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Mpla Case: I Didn't Realize Those Were The Expectations!, Samantha J Simiele, Serdar Charyyev, Liyong Lin, Leonard Kim, Dongxu Wang, Mary P Gronberg

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of how students and advisors can better communicate expectations and navigate difficult conversations. In this case, a fourth-year Ph.D. student Emma learns that her advisor Dr. So is leaving the institution and has not arranged to bring any students with him. As Emma and Dr. So meet to discuss Emma's next steps, the conversation reveals misunderstandings and miscommunications of expectations, including a specific publication requirement for graduation from Dr. So. Having just learned of …

Clinical, Endoscopic, And Histopathologic Gastrointestinal Disease In An American Cohort With Behçet's Disease, Bryan F Curtin, Kareen L Hill, Sumona Bhattacharya, Astin Powers, Aradhana Venkatesan, Preet Bagi, Elizabeth Joyal, Meghna Alimchandani, Raphaela Goldbach-Mansky, Peter Grayson, Martha Quezado, Cailin Sibley, Theo Heller

Faculty, Staff and Student Publications

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD.

METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent.

RESULTS: Eighty-three patients …

Long-Term Patient-Reported Outcomes In A Population-Based Cohort Following Radiotherapy Vs Surgery For Oropharyngeal Cancer, Michael J Dohopolski, Kevin Diao, Katherine A Hutcheson, Neil S Akhave, Ryan P Goepfert, Weiguo He, Xiudong Jennifer Lei, Susan K Peterson, Yu Shen, Baran D Sumer, Benjamin D Smith, David J Sher

Faculty, Staff and Student Publications

IMPORTANCE: Oncologic outcomes are similar for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery or radiotherapy. However, comparative differences in long-term patient-reported outcomes (PROs) between modalities are less well established.

OBJECTIVE: To determine the association between primary surgery or radiotherapy and long-term PROs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the Texas Cancer Registry to identify survivors of OPSCC treated definitively with primary radiotherapy or surgery between January 1, 2006, and December 31, 2016. Patients were surveyed in October 2020 and April 2021.

EXPOSURES: Primary radiotherapy and surgery for OPSCC.

MAIN OUTCOMES AND MEASURES: Patients completed …

Metabolomic Profile Of The Healthy Eating Index-2015 In The Multiethnic Study Of Atherosclerosis, Meghana D Gadgil, Alexis C Wood, Ibrahim Karaman, Goncalo Graça, Ioanna Tzoulaki, Victor W Zhong, Philip Greenland, Alka M Kanaya, David M Herrington

Children’s Nutrition Research Center Staff Publications

Background: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version) are limited.

Objectives: The goal was to determine a pattern of metabolites associated with the Healthy Eating Index (HEI)-2015, which measures adherence to the Dietary Guidelines for Americans.

Methods: The analysis examined 3557 adult men and women from the longitudinal cohort Multiethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens and diet and demographic questionnaires were assessed at baseline. Untargeted 1H 1-dimensional nuclei magnetic …

Factors Associated With Choice Of Behavioural Weight Loss Program By Adults With Obesity, Yasaman Jamshidi-Naeini, Susan B Roberts, Stephanie Dickinson, Arthur Owora, Jon Agley, Roger S Zoh, Xiwei Chen, David B Allison

Children’s Nutrition Research Center Staff Publications

We assessed the preference for two behavioural weight loss programs, Diabetes Prevention Program (DPP) and Healthy Weight for Living (HWL) in adults with obesity. A cross-sectional survey was fielded on the Amazon Mechanical Turk. Eligibility criteria included reporting BMI ≥30 and at least two chronic health conditions. Participants read about the programs, selected their preferred program, and answered follow-up questions. The estimated probability of choosing either program was not significantly different from .5 (N = 1005, 50.8% DPP and 49.2% HWL, p = .61). Participants' expectations about adherence, weight loss magnitude, and dropout likelihood were associated with their choice (p <  .0001). Non-White participants (p = .040) and those with monthly income greater than $4999 (p = .002) were less likely to choose DPP. Participants who had postgraduate education (p = .007), did not report high serum cholesterol (p = .028), and reported not having tried losing weight before (p = .025) were more likely to choose DPP. Those who chose HWL were marginally more likely to report that being offered two different programs rather than one would likely affect their decision to enrol in one of the two (p = .052). The enrolment into DPP and HWL was balanced, but race, educational attainment, income, previous attempt to lose weight, and serum cholesterol levels had significant associations with the choice of weight loss program.