Medical Specialties Commons^™

Targeting Idh2r140q And Other Neoantigens In Acute Myeloid Leukemia, Wingchi K Leung, Alejandro G Torres Chavez, Matthew French-Kim, Paul Shafer, Maksim Mamonkin, Laquisa C Hill, Manik Kuvalekar, Yovana Velazquez, Ayumi Watanabe, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Ann M Leen

Faculty, Staff and Students Publications

For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, ∼60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective. In this study, we explored the feasibility of immunotherapeutically targeting neoantigens, which arise from recurrent nonsynonymous mutations in AML and thus represent attractive targets because they …

The Swi/Snf Atp-Dependent Chromatin Remodeling Complex In Cell Lineage Priming And Early Development, Dhurjhoti Saha, Srinivas Animireddy, Blaine Bartholomew

Faculty, Staff and Student Publications

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell …

N-Glycoproteomic Analyses Of Human Intestinal Enteroids, Varying In Histo-Blood Group Geno- And Phenotypes, Reveal A Wide Repertoire Of Fucosylated Glycoproteins, Jonas Nilsson, Inga Rimkute, Carina Sihlbom, Victoria R Tenge, Shih-Ching Lin, Robert L Atmar, Mary K Estes, Göran Larson

Faculty, Staff and Students Publications

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs. Membrane proteins were extracted, trypsin digested, and glycopeptides enriched by hydrophilic interaction liquid chromatography and analyzed by nanoLC-MS/MS. The Byonic software was used for glycopeptide identification followed by hands-on …

Immunophenotypic Predictors Of Influenza Vaccine Immunogenicity In Pediatric Hematopoietic Cell Transplant Recipients., Justin Z. Amarin, Daniel E. Dulek, Joshua Simmons, Haya Hayek, James D. Chappell, Cindy Hager Nochowicz, Carrie L. Kitko, Jennifer E. Schuster, Flor M. Muñoz, Claire E. Bocchini, Elizabeth A. Moulton, Susan E. Coffin, Jason L. Freedman, Monica I. Ardura, Rachel L. Wattier, Gabriela Maron, Michael Grimley, Grant Paulsen, Lara Danziger-Isakov, Paul A. Carpenter, Janet A. Englund, Natasha B. Halasa, Andrew J. Spieker, Spyros A. Kalams

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and …

Structural Variants Involving Mllt10 Fusion Are Associated With Adverse Outcomes In Pediatric Acute Myeloid Leukemia., Oussama Abla, Rhonda E. Ries, Tim Triche, Robert B. Gerbing, Betsy Hirsch, Susana Raimondi, Todd Cooper, Jason E. Farrar, Nathaniel Buteyn, Lauren M. Harmon, Hong Wen, Aniruddha J. Deshpande, E Anders Kolb, Alan S. Gamis, Richard Aplenc, Todd Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis. Collectively, 127 patients (6.1%) were identified with MLLT10 fusions: 104 (81.9%) with KMT2A::MLLT10, 13 (10.2%) with PICALM::MLLT10, and 10 (7.9%) X::MLLT10: (2 each of DDX3X and TEC), with 6 partners (DDX3Y, CEP164, SCN2B, …

Modified Frailty Index Associates With Transoral Robotic Surgery Complications And Survival: A National Database Study, Amiti Jain, Zachary N. Goldberg, Erin Briggs, Dev R. Amin, Zachary D. Urdang, Richard A. Goldman, David M. Cognetti, Joseph M. Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: The modified frailty index (mFI-5) is a National Surgical Quality Improvement Program-derived 5-factor index that has been proven to reflect frailty and predict morbidity and mortality. We hypothesize that mFI-5 is a valid predictive measure in the transoral robotic surgery (TORS) population.

METHODS: Retrospective study utilizing the TriNetX US-collaborative health records network querying for TORS patients. Cohorts were stratified by mFI-5 score which uses five ICD-10 codes: nonindependent functional status, hypertension, obstructive respiratory disease, heart failure, and diabetes mellitus. Cohorts were matched by age using propensity score matching. Outcome measures included survival, infection, pneumonia, tracheostomy dependence, and percutaneous endoscopic …

Evolution Of Chromosome-Arm Aberrations In Breast Cancer Through Genetic Network Rewiring, Elena Kuzmin, Toby M Baker, Tom Lesluyes, Jean Monlong, Kento T Abe, Paula P Coelho, Michael Schwartz, Joseph Del Corpo, Dongmei Zou, Genevieve Morin, Alain Pacis, Yang Yang, Constanza Martinez, Jarrett Barber, Hellen Kuasne, Rui Li, Mathieu Bourgey, Anne-Marie Fortier, Peter G Davison, Atilla Omeroglu, Marie-Christine Guiot, Quaid Morris, Claudia L Kleinman, Sidong Huang, Anne-Claude Gingras, Jiannis Ragoussis, Guillaume Bourque, Peter Van Loo, Morag Park

Faculty, Staff and Student Publications

The basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. Analysis of The Cancer Genome Atlas data shows recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a panel of 23 primary tumor/patient-derived xenograft basal breast cancers reveals early evolution of chr4p deletion. Mechanistically we show that chr4p loss is associated with enhanced proliferation. Gene function studies identify an unknown gene, C4orf19, within chr4p, which suppresses proliferation when overexpressed-a member of the PDCD10-GCKIII kinase module …

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …

Six-Year Follow-Up And Subgroup Analyses Of A Phase 2 Trial Of Venetoclax For Del(17p) Chronic Lymphocytic Leukemia, Stephan Stilgenbauer, Eugen Tausch, Andrew W Roberts, Matthew S Davids, Barbara Eichhorst, Michael Hallek, Peter Hillmen, Christof Schneider, Johannes Schetelig, Sebastian Böttcher, Arnon P Kater, Yanwen Jiang, Michelle Boyer, Relja Popovic, Majd T Ghanim, Michael Moran, Wendy J Sinai, Xifeng Wang, Nabanita Mukherjee, Brenda Chyla, William G Wierda, John F Seymour

Faculty, Staff and Student Publications

Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982. A total of 158 patients with previously untreated (n = 5) or R/R (n = 153) del(17p) CLL received 400 mg venetoclax daily after initial ramp-up until progressive disease. After a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission …

Associations Between Stress, Health Behaviors, And Quality Of Life In Young Couples During The Transition To Survivorship: Protocol For A Measurement Burst Study, Dalnim Cho, Michael Roth, Susan K Peterson, Kristofer Jennings, Seokhun Kim, Shiao-Pei Weathers, Sairah Ahmed, J Andrew Livingston, Carlos Barcenas, Y Nancy You, Kathrin Milbury

Faculty, Staff and Student Publications

BACKGROUND: Cancer is a life-threatening, stressful event, particularly for young adults due to delays and disruptions in their developmental transitions. Cancer treatment can also cause adverse long-term effects, chronic conditions, psychological issues, and decreased quality of life (QoL) among young adults. Despite numerous health benefits of health behaviors (eg, physical activity, healthy eating, no smoking, no alcohol use, and quality sleep), young adult cancer survivors report poor health behavior profiles. Determining the associations of stress (either cancer-specific or day-to-day stress), health behaviors, and QoL as young adult survivors transition to survivorship is key to understanding and enhancing these survivors' health. …

Correlational Analysis Of Sarcopenia And Multimorbidity Among Older Inpatients, Wenjing Xia, Kang Luo, Ziwei Gu, Jianping Hu, Xintong Liu, Qian Xiao

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two.

METHODS: The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in …

Comprehensive Guidance For The Prevention Of Periprosthetic Joint Infection After Total Joint Arthroplasty And Pitfalls In The Prevention, Javad Parvizi, Yonghan Cha, Emanuele Chisari, Kangbaek Kim, Kyung-Hoi Koo

Rothman Institute Papers

Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA. With the increasing volume …

Real-World Outcomes For The Fifth-Generation Balloon Expandable Transcatheter Heart Valve In The United States., Curtiss T Stinis, Amr E Abbas, Paul Teirstein, Raj R Makkar, Christine J Chung, Vijay Iyer, Philippe Généreux, Robert M Kipperman, John K Harrison, G Chad Hughes, Jefferson M Lyons, Ayaz Rahman, Nikolaos Kakouros, Jennifer Walker, David K Roberts, Pei-Hsiu Huang, Biswajit Kar, Abhijeet Dhoble, Daniel P Logsdon, Puneet K Khanna, Joseph Aragon, James M Mccabe

Heart and Vascular Articles

BACKGROUND: The fifth-generation SAPIEN 3 Ultra Resilia valve (S3UR) incorporates several design changes as compared with its predecessors, the SAPIEN 3 (S3) and SAPIEN 3 Ultra (S3U) valves, including bovine leaflets treated with a novel process intended to reduce structural valve deterioration via calcification, as well as a taller external skirt on the 29-mm valve size to reduce paravalvular leak (PVL). The clinical performance of S3UR compared with S3 and S3U in a large patient population has not been previously reported.

OBJECTIVES: The aim of this study was to compare S3UR to S3/S3U for procedural, in-hospital, and 30-day clinical and …

An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide …

Association Between Antenatal Vaginal Bleeding And Adverse Perinatal Outcomes In Placenta Accreta Spectrum, J Connor Mulhall, Kayla E Ireland, John J Byrne, Patrick S Ramsey, Georgia A Mccann, Jessian L Munoz

Faculty, Staff and Student Publications

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal …

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …

Diffuse Hemispheric Glioma With H3 P.K28m (K27m) Mutation: Unusual Non-Midline Presentation Of Diffuse Midline Glioma, H3 K27m-Altered?, Kliment Donev, Vanitha Sundararajan, Derek Johnson, Jagadheshwar Balan, Meagan Chambers, Vera A Paulson, Kathryn P Scherpelz, Zied Abdullaev, Martha Quezado, Patrick J Cimino, Drew Pratt, Ediel Valerio, João Vıctor Alves De Castro, Dirce Maria Carraro, Giovana Tardin Torrezan, Beatriz Martins Wolff, Leslie Domenici Kulikowski, Felipe D'Almeida Costa, Kenneth Aldape, Cristiane M Ida

Neuroscience Articles

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in …

Mapping Of Alzheimer’S Disease Related Data Elements And The Nih Common Data Elements, Xubing Hao, Rashmie Abeysinghe, Fengbo Zheng, Paul E Schulz, The Alzheimer’S Disease Neuroimaging Initiative, Licong Cui

Faculty, Staff and Student Publications

Background

Alzheimer’s Disease (AD) is a devastating disease that destroys memory and other cognitive functions. There has been an increasing research effort to prevent and treat AD. In the US, two major data sharing resources for AD research are the National Alzheimer’s Coordinating Center (NACC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI); Additionally, the National Institutes of Health (NIH) Common Data Elements (CDE) Repository has been developed to facilitate data sharing and improve the interoperability among data sets in various disease research areas.

Method

To better understand how AD-related data elements in these resources are interoperable with each other, we …

Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung

Children’s Nutrition Research Center Staff Publications

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before …

Perspectives From Patients With Chronic Lung Disease On A Telehealth-Facilitated Integrated Palliative Care Model: A Qualitative Content Analysis Study, Jeannette Kates, Carrie Tompkins Stricker, Kristin L. Rising, Alexzandra Gentsch, Ellen Solomon, Victoria Powers, Venise J. Salcedo, Brooke Worster

Department of Medicine Faculty Papers

BACKGROUND: Chronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing.

METHODS: For this qualitative …

Durability Of Original Monovalent Mrna Vaccine Effectiveness Against Covid-19 Omicron-Associated Hospitalization In Children And Adolescents - United States, 2021-2023., Laura D. Zambrano, Margaret M. Newhams, Regina M. Simeone, Amanda B. Payne, Michael Wu, Amber O. Orzel-Lockwood, Natasha B. Halasa, Jemima M. Calixte, Pia S. Pannaraj, Kanokporn Mongkolrattanothai, Julie A Boom, Leila C Sahni, Satoshi Kamidani, Kathleen Chiotos, Melissa A Cameron, Aline B Maddux, Katherine Irby, Jennifer E. Schuster, Elizabeth H. Mack, Austin Biggs, Bria M. Coates, Kelly N. Michelson, Katherine E. Bline, Ryan A. Nofziger, Hillary Crandall, Charlotte V. Hobbs, Shira J. Gertz, Sabrina M. Heidemann, Tamara T. Bradford, Tracie C. Walker, Stephanie P. Schwartz, Mary Allen Staat, Samina S. Bhumbra, Janet R. Hume, Michele Kong, Melissa S. Stockwell, Thomas J. Connors, Melissa L. Cullimore, Heidi R. Flori, Emily R. Levy, Natalie Z. Cvijanovich, Matt S. Zinter, Mia Maamari, Cindy Bowens, Danielle M. Zerr, Judith A. Guzman-Cottrill, Ivan Gonzalez, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite …

Transposable Elements Regulate Thymus Development And Function, Jean-David Larouche, Céline M Laumont, Assya Trofimov, Krystel Vincent, Leslie Hesnard, Sylvie Brochu, Caroline Côté, Juliette F Humeau, Éric Bonneil, Joel Lanoix, Chantal Durette, Patrick Gendron, Jean-Philippe Laverdure, Ellen R Richie, Sébastien Lemieux, Pierre Thibault, Claude Perreault

Faculty, Staff and Student Publications

Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multiomic analyses of TEs in human and mouse thymic cells to elucidate their role in T-cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TE expression correlates with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: …

Academic Detailing As A Health Information Technology Implementation Method: Supporting The Design And Implementation Of An Emergency Department-Based Clinical Decision Support Tool To Prevent Future Falls, Hanna J Barton, Apoorva Maru, Margaret A Leaf, Daniel J Hekman, Douglas A Wiegmann, Manish N Shah, Brian W Patterson

Faculty, Staff and Student Publications

BACKGROUND: Clinical decision support (CDS) tools that incorporate machine learning-derived content have the potential to transform clinical care by augmenting clinicians' expertise. To realize this potential, such tools must be designed to fit the dynamic work systems of the clinicians who use them. We propose the use of academic detailing-personal visits to clinicians by an expert in a specific health IT tool-as a method for both ensuring the correct understanding of that tool and its evidence base and identifying factors influencing the tool's implementation.

OBJECTIVE: This study aimed to assess academic detailing as a method for simultaneously ensuring the correct …

Human Dna Polymerase Θ Does Not Harbor Intrinsic Nuclease Activity, Denisse Carvajal-Maldonado, Karl Zahn, Ryan Jensen, Richard D Wood, Sylvie Doublié

Faculty, Staff and Student Publications

No abstract provided.

Cdk8/Cdk19 Promotes Mitochondrial Fission Through Drp1 Phosphorylation And Can Phenotypically Suppress Pink1 Deficiency In Drosophila, Jenny Zhe Liao, Hyung-Lok Chung, Claire Shih, Kenneth Kin Lam Wong, Debdeep Dutta, Zelha Nil, Catherine Grace Burns, Oguz Kanca, Ye-Jin Park, Zhongyuan Zuo, Paul C Marcogliese, Katherine Sew, Hugo J Bellen, Esther M Verheyen

Faculty, Staff and Students Publications

Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated mitochondria in both muscles and neurons. We find that endogenous GFP-tagged Cdk8 can be found in both the cytoplasm and nucleus. …

Somatic Mutations Of Esophageal Adenocarcinoma: A Comparison Between Black And White Patients, Hyeyeun Lim, Marie-Claude Gingras, Jing Zhao, Jinyoung Byun, Patricia D Castro, Spiridon Tsavachidis, Jianhong Hu, Harshavardhan Doddapaneni, Yi Han, Donna M Muzny, Richard A Gibbs, Christopher I Amos, Aaron P Thrift

Faculty, Staff and Students Publications

Esophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational …

Fourteen-Day Vonoprazan-Based Bismuth Quadruple Therapy For H Pylori Eradication In An Area With High Clarithromycin And Levofloxacin Resistance: A Prospective Randomized Study (Vq-Hp Trial), Nuttapat Tungtrongchitr, Phubordee Bongkotvirawan, Sarita Ratana-Amornpin, Sith Siramolpiwat, Thanee Eiamsitrakoon, Pornpen Gamnarai, Arti Wongcha-Um, Yoshio Yamaoka, Kammal Kumar Pawa, Ratha-Korn Vilaichone

Faculty, Staff and Students Publications

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, …

Relating Preoperative Mcs-12 To Microdiscectomy Outcomes, Jeremy C. Heard, Yunsoo Lee, Teeto Ezeonu, Mark J. Lambrechts, Rajkishen Narayanan, Caleb Yeung, Justin Wright, John Paulik, Caroline Purtill, John J. Mangan, Mark F. Kurd, Ian D. Kaye, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Rothman Institute Papers

PURPOSE: To determine the impact of poor mental health on patient-reported and surgical outcomes after microdiscectomy.

METHODS: Patients ≥ 18 years who underwent a single-level lumbar microdiscectomy from 2014 to 2021 at a single academic institution were retrospectively identified. Patient-reported outcomes (PROMs) were collected at preoperative, three-month, and one-year postoperative time points. PROMs included the Oswestry Disability Index (ODI), Visual Analog Scale Back and Leg (VAS Back and VAS Leg, respectively), and the mental and physical component of the short form-12 survey (MCS and PCS). The minimum clinically important differences (MCID) were employed to compare scores for each PROM. Patients …

Improved Data Quality And Statistical Power Of Trial-Level Event-Related Potentials With Bayesian Random-Shift Gaussian Processes, Dustin Pluta, Beniamino Hadj-Amar, Meng Li, Yongxiang Zhao, Francesco Versace, Marina Vannucci

Faculty, Staff and Student Publications

Studies of cognitive processes via electroencephalogram (EEG) recordings often analyze group-level event-related potentials (ERPs) averaged over multiple subjects and trials. This averaging procedure can obscure scientifically relevant variability across subjects and trials, but has been necessary due to the difficulties posed by inference of trial-level ERPs. We introduce the Bayesian Random Phase-Amplitude Gaussian Process (RPAGP) model, for inference of trial-level amplitude, latency, and ERP waveforms. We apply RPAGP to data from a study of ERP responses to emotionally arousing images. The model estimates of trial-specific signals are shown to greatly improve statistical power in detecting significant differences in experimental conditions …

Regimen For Accelerated Propranolol Initial Dosing (Rapid), Charles Y. Huang, Marissa J. Perman, Albert C. Yan

Student Papers, Posters & Projects

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day.

METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas …