Medicine and Health Sciences Commons^™

Spatially Resolved Single-Cell Assessment Of Pancreatic Cancer Expression Subtypes Reveals Co-Expressor Phenotypes And Extensive Intratumoral Heterogeneity, Hannah L Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S Winter, Kevin S Kapner, Scott P Ginebaugh, Sara A Väyrynen, Juha P Väyrynen, Chen Yuan, Andrew W Navia, Junning Wang, Annan Yang, Timothy L Bosse, Radha L Kalekar, Kristen E Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A Rubinson, Harshabad Singh, Kimberly Perez, James M Cleary, Thomas E Clancy, Jiping Wang, Joseph D Mancias, Lauren K Brais, Emma R Hill, Margaret M Kozak, David C Linehan, Richard F Dunne, Daniel T Chang, Albert C Koong, Aram F Hezel, William C Hahn, Alex K Shalek, Andrew J Aguirre, Jonathan A Nowak, Brian M Wolpin

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed …

Lef1 Drives A Central Memory Program And Supports Antitumor Activity Of Natural Killer T Cells, Ho Ngai, Gabriel A Barragan, Gengwen Tian, Julien C Balzeau, Chunchao Zhang, Amy N Courtney, Linjie Guo, Xin Xu, Michael S Wood, Janice M Drabek, Thorsten Demberg, Caroline M Sands, Cynthia N Chauvin-Fleurence, Erica J Di Pierro, Jeffrey M Rosen, Leonid S Metelitsa

Faculty, Staff and Students Publications

Vα24-invariant natural killer T cells (NKT) possess innate antitumor properties that can be exploited for cancer immunotherapy. We have shown previously that the CD62L+ central memory-like subset of these cells drives the in vivo antitumor activity of NKTs, but molecular mediators of NKT central memory differentiation remain unknown. Here, we demonstrate that relative to CD62L- cells, CD62L+ NKTs express a higher level of the gene encoding the Wnt/β-catenin transcription factor lymphoid enhancer binding factor 1 (LEF1) and maintain active Wnt/β-catenin signaling. CRISPR/Cas9-mediated LEF1 knockout reduced CD62L+ frequency after antigenic stimulation, whereas Wnt/β-catenin activator Wnt3a ligand increased CD62L+ frequency. LEF1 overexpression …

Genome-Wide Screening Reveals The Genetic Basis Of Mammalian Embryonic Eye Development, Justine M Chee, Louise Lanoue, Dave Clary, Kendall Higgins, Lynette Bower, Ann Flenniken, Ruolin Guo, David J Adams, Fatima Bosch, Robert E Braun, Steve D M Brown, H-J Genie Chin, Mary E Dickinson, Chih-Wei Hsu, Michael Dobbie, Xiang Gao, Sanjeev Galande, Anne Grobler, Jason D Heaney, Yann Herault, Martin Hrabe De Angelis, Fabio Mammano, Lauryl M J Nutter, Helen Parkinson, Chuan Qin, Toshi Shiroishi, Radislav Sedlacek, J-K Seong, Ying Xu, Brian Brooks, Colin Mckerlie, K C Kent Lloyd, Henrik Westerberg, Ala Moshiri

Faculty, Staff and Students Publications

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways …

Alternative Polyadenylation Transcriptome-Wide Association Study Identifies Apa-Linked Susceptibility Genes In Brain Disorders, Ya Cui, Frederick J Arnold, Fanglue Peng, Dan Wang, Jason Sheng Li, Sebastian Michels, Eric J Wagner, Albert R La Spada, Wei Li

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) plays an essential role in brain development; however, current transcriptome-wide association studies (TWAS) largely overlook APA in nominating susceptibility genes. Here, we performed a 3' untranslated region (3'UTR) APA TWAS (3'aTWAS) for 11 brain disorders by combining their genome-wide association studies data with 17,300 RNA-seq samples across 2,937 individuals. We identified 354 3'aTWAS-significant genes, including known APA-linked risk genes, such as SNCA in Parkinson's disease. Among these 354 genes, ~57% are not significant in traditional expression- and splicing-TWAS studies, since APA may regulate the translation, localization and protein-protein interaction of the target genes independent of mRNA level …

Microbes, Histology, Blood Analysis, Enterotoxins, And Cytokines: Findings From The Aserf Systemic Symptoms In Women-Biospecimen Analysis Study: Part 3, Patricia Mcguire, Caroline Glicksman, Roger Wixtrom, C James Sung, Robert Hamilton, Marisa Lawrence, Melinda Haws, Sarah Ferenz, Marshall Kadin

2020-Current year OA Pubs

BACKGROUND: There has been an increasing need to acquire rigorous scientific data to answer the concerns of physicians, patients, and the FDA regarding the self-reported illness identified as breast implant illness (BII). There are no diagnostic tests or specific laboratory values to explain the reported systemic symptoms described by these patients.

OBJECTIVES: The aim of this study was to determine if there are quantifiable laboratory findings that can be identified in blood, capsule tissue pathology, or microbes that differentiate women with systemic symptoms they attribute to their implants from 2 control groups.

METHODS: A prospective blinded study enrolled 150 subjects …

Binding Peptide Generation For Mhc Class I Proteins With Deep Reinforcement Learning, Ziqi Chen, Baoyi Zhang, Hongyu Guo, Prashant Emani, Trevor Clancy, Chongming Jiang, Mark Gerstein, Xia Ning, Chao Cheng, Martin Renqiang Min

Faculty, Staff and Students Publications

Motivation: MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of peptides for various MHC Class I proteins are distinct, which can be reflected by their diverse binding motifs. To characterize binding motifs for MHC Class I proteins, in vitro experiments have been conducted to screen peptides with high binding affinities to hundreds of given MHC Class I proteins. However, considering tens of thousands of known MHC Class I proteins, conducting in vitro experiments for extensive MHC proteins is infeasible, and thus a more efficient and scalable way to …

Tumor-Associated Nonmyelinating Schwann Cell-Expressed Nuclear Export Signal Mutation Of Epidermal Growth Factor Receptor Enhances Malignant Phenotypes Of Cancer Cells, Chengcao Sun, Youqiong Ye, Zhi Tan, Yuan Liu, Yajuan Li, Wei Hu, Ke Liang, Sergey D Egranov, Lisa Angela Huang, Zhao Zhang, Yaohua Zhang, Jun Yao, Tina K Nguyen, Zilong Zhao, Andrew Wu, Jeffrey R Marks, Abigail S Caudle, Aysegul A Sahin, Jianjun Gao, Seth T Gammon, David Piwnica-Worms, Jian Hu, Paul J Chiao, Dihua Yu, Mien-Chie Hung, Michael A Curran, George A Calin, Haoqiang Ying, Leng Han, Chunru Lin, Liuqing Yang

Faculty, Staff and Student Publications

One of the major obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is its immunoresistant microenvironment. The functional importance and molecular mechanisms of Schwann cells in PDAC remains largely elusive. We characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc) in PDAC and indicated that the abundance of TASc was correlated with immune suppressive tumor microenvironment and the unfavorable outcome of patients with PDAC. Depletion of pancreatic-specific TASc promoted the tumorigenesis of PDAC tumors. TASc-expressed long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (

Immunogenetic Determinants Of Susceptibility To Head And Neck Cancer In The Million Veteran Program Cohort, Yanhong Liu, Jennifer R Kramer, Vlad C Sandulache, Robert Yu, Guojun Li, Liang Chen, Zenab I Yusuf, Yunling Shi, Saiju Pyarajan, Spyros Tsavachidis, Li Jiao, Michelle L Mierzwa, Elizabeth Chiao, Yvonne M Mowery, Andrew Shuman, Sanjay Shete, Andrew G Sikora, Donna L White

Faculty, Staff and Student Publications

Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and …

Association Between P2y12 Inhibitor Reloading And In-Hospital Outcomes For Patients With Non-St-Segment Elevation Acute Coronary Syndrome Already On Chronic P2y12 Receptor Inhibitors Therapy In China: Findings From The Ccc-Acs (Improving Care For Cardiovascular Disease In China-Acute Coronary Syndrome) Project, Yintang Wang, Yu Geng, Ou Zhang, Qin Xu, Yajun Xue, Boda Zhou, Ping Zhang

Faculty, Staff and Student Publications

BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined.

METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted.

RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk …

Effective Treatment Of Low-Risk Acute Gvhd With Itacitinib Monotherapy, Aaron Etra, Alexandra Capellini, Amin Alousi, Monzr M Al Malki, Hannah Choe, Zachariah Defilipp, William J Hogan, Carrie L Kitko, Francis Ayuk, Janna Baez, Isha Gandhi, Stelios Kasikis, Sigrun Gleich, Elizabeth Hexner, Matthias Hoepting, Urvi Kapoor, Steven Kowalyk, Deukwoo Kwon, Amelia Langston, Marco Mielcarek, George Morales, Umut Özbek, Muna Qayed, Ran Reshef, Wolf Rösler, Nikolaos Spyrou, Rachel Young, Yi-Bin Chen, James L M Ferrara, John E Levine

Faculty, Staff and Student Publications

The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those …

Presence Of Symptoms 6 Weeks After Covid-19 Among Vaccinated And Unvaccinated Us Healthcare Personnel: A Prospective Cohort Study, Nicholas M. Mohr, Ian D. Plumb, Kari K. Harland, Tamara Pilishvili, Katherine E. Fleming-Dutra, Anusha Krishnadasan, Karin F. Hoth, Sharon H. Saydah, Zachary Mankoff, John P. Haran, Melissa Briggs-Hagen, Eliezer Santos León, David A. Talan

Department of Emergency Medicine Faculty Papers

OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work.

DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset.

SETTING: Health systems in 12 US states.

PARTICIPANTS: HCP participating …

Insights Into Cell-Specific Functions Of Microtubules In Skeletal Muscle Development And Homeostasis, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

The contractile cells of skeletal muscles, called myofibers, are elongated multinucleated syncytia formed and maintained by the fusion of proliferative myoblasts. Human myofibers can be hundreds of microns in diameter and millimeters in length. Myofibers are non-mitotic, obviating the need for microtubules in cell division. However, microtubules have been adapted to the unique needs of these cells and are critical for myofiber development and function. Microtubules in mature myofibers are highly dynamic, and studies in several experimental systems have demonstrated the requirements for microtubules in the unique features of muscle biology including myoblast fusion, peripheral localization of nuclei, assembly of …

A Multicenter Study Of Clinical Impact Of Variant Of Uncertain Significance Reclassification In Breast, Ovarian And Colorectal Cancer Susceptibility Genes., Sukh Makhnoon, Brooke Levin, Megan Ensinger, Kristin Mattie, Robert J Volk, Zhongming Zhao, Tito Mendoza, Sanjay Shete, Laila Samiian, Generosa Grana, Andrew Grainger, Banu Arun, Brian H Shirts, Susan K Peterson

Oncology Articles

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.

METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) …

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …

Association Between Measures Of Cognitive Function On Physical Function In Novice Users Of A Lower Limb Prosthesis, Humberto Omana, Courtney Frengopoulos, Manuel Montero-Odasso, Michael W. Payne, Ricardo Viana, Susan W. Hunter

Physical Therapy Publications

BACKGROUND: Cognitive impairment is prevalent in people with lower limb amputations (PLLA) and is associated with adverse outcomes, such as falls and worse rehabilitation outcomes. Physical function tests are essential to examine abilities; however, no research in PLLA has clarified the magnitude of cognitive demands amongst available tests in users novice at walking with a prosthesis.

METHODS: People from inpatient prosthetic rehabilitation were recruited. Inclusion criteria were: age ≥ 50 years, unilateral transtibial amputation and able to walk independently. Gait velocity and the L Test under single-task (usual) and dual-task (walking while counting backwards) conditions assessed functional mobility. The Four …

Neighborhood Deprivation And Residential Property Values Do Not Affect Weight Loss At 1 Or 3 Years After Bariatric Surgery, Adam Drewnowski, Benjamin D Hong, Ernest Shen, Ming Ji, Silvia R Paz, Bhumi B Bhakta, Mayra Macias, Cecelia L Crawford, Kristina H Lewis, Jialuo Liu, Darren D Moore, Sameer B Murali, Deborah R Young, Karen J Coleman

Faculty, Staff and Student Publications

OBJECTIVE: This study examined the association between individual- and neighborhood-level sociodemographic factors and surgical weight loss at 1 year (short term) and 3 years (long term).

METHODS: Data were obtained from the baseline survey of the BELONG (Bariatric Experience Long Term) prospective longitudinal cohort study. Individual-level self-reported data on sex, race and ethnicity, education, and household income were obtained by survey. Data from the 2010 US Census were used to calculate area Neighborhood Deprivation Index score and median value of owner-occupied housing units at the census tract level.

RESULTS: Patients (N = 1341) had a mean age of 43.4 (SD …

Early Feasibility Of Endovascular Repair Of Distal Aortic Arch Aneurysms Using Patient-Specific Single Retrograde Left Subclavian Artery Branch Stent Graft, Joshua Wong, Emanuel R Tenorio, Guilherme Lima, Marina Dias-Neto, Aidin Baghbani-Oskouei, Bernardo Mendes, Jarin Kratzberg, Laura Ocasio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

OBJECTIVE: To describe the feasibility and outcomes of endovascular repair of distal aortic arch aneurysms using a patient-specific stent graft with a pre-loaded single retrograde left subclavian artery (LSA) branch stent graft.

METHODS: We reviewed the clinical data and outcomes of consecutive patients enrolled in an ongoing prospective, non-randomized physician-sponsored investigational device exemption study to evaluate the outcomes of endovascular aortic arch repair using patient-specific arch branch stent grafts (William Cook Europe, Bjaeverskov, Denmark) between 2019 and 2022. All patients received a design with triple-wide scallop and a single retrograde LSA branch with a pre-loaded catheter.

RESULTS: There were five …

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays In Icu Admitted Patients, David J Roh, Tiffany R Chang, Aditya Kumar, Devin Burke, Glenda Torres, Katherine Xu, Winni Yang, Azzurra Cottarelli, Ernest Moore, Angela Sauaia, Kirk Hansen, Angela Velazquez, Amelia Boehme, Athina Vrosgou, Shivani Ghoshal, Soojin Park, Sachin Agarwal, Jan Claassen, E Sander Connolly, Gebhard Wagener, Richard O Francis, Eldad Hod

Faculty, Staff and Student Publications

Objectives: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

Design: Observational cohort study and separate in vitro laboratory study.

Setting: Multicenter tertiary referral ICUs.

Patients: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory …

Automated Field-In-Field Whole Brain Radiotherapy Planning, Kai Huang, Soleil Hernandez, Chenyang Wang, Callistus Nguyen, Tina Marie Briere, Carlos Cardenas, Laurence Court, Yao Xiao

Faculty, Staff and Student Publications

PURPOSE: We developed and tested an automatic field-in-field (FIF) solution for whole-brain radiotherapy (WBRT) planning that creates a homogeneous dose distribution by minimizing hotspots, resulting in clinically acceptable plans.

METHODS: A configurable auto-planning algorithm was developed to automatically generate FIF WBRT plans independent of the treatment planning system. Configurable parameters include the definition of hotspots, target volume, maximum number of subfields, and minimum number of monitor units per field. This algorithm iteratively identifies a hotspot, creates two opposing subfields, calculates the dose, and optimizes the beam weight based on user-configured constraints of dose-volume histogram coverage and least-squared cost functions. The …

Biological Correlates Of The Effects Of Auricular Point Acupressure On Pain, Chao Hsing Yeh, Nada Lukkahatai, Xinran Huang, Hulin Wu, Hongyu Wang, Jingyu Zhang, Xinyi Sun, Thomas J Smith

Faculty, Staff and Student Publications

BACKGROUND: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers.

DESIGN: This is a secondary data analysis.

METHODS: Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for …

Machine Learning And Acute Stroke Imaging, Sunil A Sheth, Luca Giancardo, Marco Colasurdo, Visish M Srinivasan, Arash Niktabe, Peter Kan

Faculty, Staff and Student Publications

BACKGROUND: In recent years, machine learning (ML) has had notable success in providing automated analyses of neuroimaging studies, and its role is likely to increase in the future. Thus, it is paramount for clinicians to understand these approaches, gain facility with interpreting ML results, and learn how to assess algorithm performance.

OBJECTIVE: To provide an overview of ML, present its role in acute stroke imaging, discuss methods to evaluate algorithms, and then provide an assessment of existing approaches.

METHODS: In this review, we give an overview of ML techniques commonly used in medical imaging analysis and methods to evaluate performance. …

Alphaviruses Detected In Mosquitoes In The North-Eastern Regions Of South Africa, 2014 To 2018, Milehna M Guarido, Isabel Fourie, Kgothatso Meno, Adriano Mendes, Megan A Riddin, Caitlin Macintyre, Sontaga Manyana, Todd Johnson, Maarten Schrama, Erin E Gorsich, Basil D Brooke, Antonio Paulo G Almeida, Marietjie Venter

Faculty, Staff and Student Publications

The prevalence and distribution of African alphaviruses such as chikungunya have increased in recent years. Therefore, a better understanding of the local distribution of alphaviruses in vectors across the African continent is important. Here, entomological surveillance was performed from 2014 to 2018 at selected sites in north-eastern parts of South Africa where alphaviruses have been identified during outbreaks in humans and animals in the past. Mosquitoes were collected using a net, CDC-light, and BG-traps. An alphavirus genus-specific nested RT-PCR was used for screening, and positive pools were confirmed by sequencing and phylogenetic analysis. We collected 64,603 mosquitoes from 11 genera, …

A Multicenter Study Of Clinical Impact Of Variant Of Uncertain Significance Reclassification In Breast, Ovarian And Colorectal Cancer Susceptibility Genes, Sukh Makhnoon, Brooke Levin, Megan Ensinger, Kristin Mattie, Robert J Volk, Zhongming Zhao, Tito Mendoza, Sanjay Shete, Laila Samiian, Generosa Grana, Andrew Grainger, Banu Arun, Brian H Shirts, Susan K Peterson

Faculty, Staff and Student Publications

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.

METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) …

Impact Of Us Preventive Services Task Force Lung Cancer Screening Update On Drivers Of Disparities In Screening Eligibility, Kristin G Maki, Rajesh Talluri, Iakovos Toumazis, Sanjay Shete, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: In 2021, the U.S. Preventive Services Task Force (USPSTF) updated its recommendation to expand lung cancer screening (LCS) eligibility and mitigate disparities. Although this increased the number of non-White individuals who are eligible for LCS, the update's impact on drivers of disparities is less clear. This analysis focuses on racial disparities among Black individuals because members of this group disproportionately share late-stage lung cancer diagnoses, despite typically having a lower intensity smoking history compared to non-Hispanic White individuals.

METHODS: We used data from the National Health Interview Survey to examine the impact of the 2021 eligibility criteria on racial …

Aapm Btsc Report 377: Physicist Brachytherapy Training In 2021-A Survey Of Therapeutic Medical Physics Residency Program Directors, Manik Aima, Samantha J Simiele, Susan L Richardson, Christopher S Melhus

Faculty, Staff and Student Publications

BACKGROUND: Brachytherapy (BT) was the first radiotherapeutic technique used to treat human disease and remains an essential modality in radiation oncology. A decline in the utilization of BT as a treatment modality has been observed and reported, which may impact training opportunities for medical physics residents. A survey of therapeutic medical physics residency program directors was performed as part of an assessment of the current state of BT training during residency.

METHODS: In March 2021, a survey consisting of 23 questions was designed by a working unit of the Brachytherapy Subcommittee of the American Association of Physicists in Medicine (AAPM) …

Structural Basis For Transcription Factor Zbtb7a Recognition Of Dna And Effects Of Zbtb7a Somatic Mutations That Occur In Human Acute Myeloid Leukemia, Ren Ren, John R Horton, Qin Chen, Jie Yang, Bin Liu, Yun Huang, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to …

The Orf7a Protein Of Sars-Cov-2 Initiates Autophagy And Limits Autophagosome-Lysosome Fusion Via Degradation Of Snap29 To Promote Virus Replication, Peili Hou, Xuefeng Wang, Hongmei Wang, Tiecheng Wang, Zhangping Yu, Chunqing Xu, Yudong Zhao, Wenqi Wang, Yong Zhao, Fengyun Chu, Huasong Chang, Hongchao Zhu, Jiahui Lu, Fuzhen Zhang, Xue Liang, Xingyu Li, Song Wang, Yuwei Gao, Hongbin He

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the …

Biomarkers For Dementia In Latin American Countries: Gaps And Opportunities, Mario A Parra, Paulina Orellana, Tomas Leon, Cabello G Victoria, Fernando Henriquez, Rodrigo Gomez, Constanza Avalos, Andres Damian, Andrea Slachevsky, Agustin Ibañez, Henrik Zetterberg, Betty M Tijms, Jennifer S Yokoyama, Stefanie D Piña-Escudero, J Nicholas Cochran, Diana L Matallana, Daisy Acosta, Ricardo Allegri, Bianca P Arias-Suárez, Bernardo Barra, Maria Isabel Behrens, Sonia M D Brucki, Geraldo Busatto, Paulo Caramelli, Sheila Castro-Suarez, Valeria Contreras, Nilton Custodio, Sergio Dansilio, Myriam De La Cruz-Puebla, Leonardo Cruz De Souza, Monica M Diaz, Lissette Duque, Gonzalo A Farías, Sergio T Ferreira, Nahuel Magrath Guimet, Ana Kmaid, David Lira, Francisco Lopera, Beatriz Mar Meza, Eliane C Miotto, Ricardo Nitrini, Alberto Nuñez, Santiago O'Neill, John Ochoa, Maritza Pintado-Caipa, Elisa De Paula França Resende, Shannon Risacher, Luz Angela Rojas, Valentina Sabaj, Lucas Schilling, Allis F Sellek, Ana Sosa, Leonel T Takada, Antonio L Teixeira, Martha Unaucho-Pilalumbo, Claudia Duran-Aniotz

Faculty, Staff and Student Publications

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a …

Circulation Of Rhinoviruses And/Or Enteroviruses In Pediatric Patients With Acute Respiratory Illness Before And During The Covid-19 Pandemic In The Us., Danielle A. Rankin, Andrew J. Spieker, Ariana Perez, Anna L. Stahl, Herdi K. Rahman, Laura S. Stewart, Jennifer E. Schuster, Joana Y. Lively, Zaid Haddadin, Varvara Probst, Marian G. Michaels, John V. Williams, Julie A. Boom, Leila C. Sahni, Mary A. Staat, Elizabeth P. Schlaudecker, Monica M. Mcneal, Christopher J. Harrison, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Susan I. Gerber, Meredith Mcmorrow, Brian Rha, James D. Chappell, Rangaraj Selvarangan, Claire M. Midgley, Natasha B. Halasa, Nvsn Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting.

OBJECTIVE: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought …

Oral Ibrexafungerp For Vulvovaginal Candidiasis Treatment: An Analysis Of Vanish 303 And Vanish 306, Oluwatosin Goje, Ryan Sobel, Paul Nyirjesy, Steven R Goldstein, Mark Spitzer, Brooke Faught, Shelagh Larson, Thomas King, Nkechi E Azie, David Angulo, Jack D Sobel

Department of Obstetrics and Gynecology Faculty Papers

Background: Ibrexafungerp is a novel antifungal treatment for acute vulvovaginal candidiasis (VVC). Using pooled data from two phase three studies (VANISH 303 and 306) in the treatment of acute VVC, this analysis sought to determine the effectiveness of ibrexafungerp in various patient subgroups that may impact outcomes. Materials and Methods: Data from VANISH 303 (NCT03734991) and VANISH 306 (NCT03987620) evaluating ibrexafungerp 300 mg twice daily (BID) for 1 day versus placebo, were pooled and analyzed to determine clinical cure rate, clinical improvement, and mycological cure at the test-of-cure visit (day 11 ± 3) and symptom resolution …