Medical Specialties Commons^™

The Role Of Native Cysteine Residues In The Oligomerization Of Kcnq1 Channels, Alison Bates, Rebecca B Stowe, Elizabeth M Travis, Lauryn E Cook, Carole Dabney-Smith, Gary A Lorigan

Faculty, Staff and Student Publications

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal …

Utility Of Patient-Reported Symptom And Functional Outcomes To Indicate Recovery After First 90 Days Of Radical Cystectomy: A Longitudinal Study, Xin Shelley Wang, Kelly K Bree, Neema Navai, Mona Kamal, Shu-En Shen, Elizabeth Letona, Charles S Cleeland, Qiuling Shi, Vijaya Gottumukkala

Faculty, Staff and Student Publications

This is a longitudinal prospective study that tracked multiple symptom burden and functioning status for bladder cancer (BLC) patients for 3 months post-radical cystectomy at The University of Texas MD Anderson Cancer Center, using a validated disease-specific patient-reported outcome measure (PROM) tool, the MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). The feasibility of collecting an objective measure for physical functioning, using "Timed Up & Go test" (TUGT) and PRO scores at baseline, discharge and end of study, was tested. Patients (

Digital Health Technologies For Peripartum Depression Management Among Low-Socioeconomic Populations: Perspectives From Patients, Providers, And Social Media Channels, Alexandra Zingg, Tavleen Singh, Amy Franklin, Angela Ross, Sudhakar Selvaraj, Jerrie Refuerzo, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Peripartum Depression (PPD) affects approximately 10-15% of perinatal women in the U.S., with those of low socioeconomic status (low-SES) more likely to develop symptoms. Multilevel treatment barriers including social stigma and not having appropriate access to mental health resources have played a major role in PPD-related disparities. Emerging advances in digital technologies and analytics provide opportunities to identify and address access barriers, knowledge gaps, and engagement issues. However, most market solutions for PPD prevention and management are produced generically without considering the specialized needs of low-SES populations. In this study, we examine and portray the information and technology needs …

Cxcr2 Expression During Melanoma Tumorigenesis Controls Transcriptional Programs That Facilitate Tumor Growth, J Yang, K Bergdorf, C Yan, W Luo, S C Chen, G D Ayers, Q Liu, X Liu, M Boothby, V L Weiss, S M Groves, A N Oleskie, X Zhang, D Y Maeda, J A Zebala, V Quaranta, A Richmond

Faculty, Staff and Student Publications

Background: Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established.

Methods: To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten-/-/Cxcr2-/- and NRasQ61R/INK4a-/-/Cxcr2-/- melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten-/- and NRasQ61R/INK4a-/- mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, …

A Single-Cell Trajectory Atlas Of Striatal Development, Ashley G Anderson, Ashwinikumar Kulkarni, Genevieve Konopka

Faculty, Staff and Students Publications

The striatum integrates dense neuromodulatory inputs from many brain regions to coordinate complex behaviors. This integration relies on the coordinated responses from distinct striatal cell types. While previous studies have characterized the cellular and molecular composition of the striatum using single-cell RNA-sequencing at distinct developmental timepoints, the molecular changes spanning embryonic through postnatal development at the single-cell level have not been examined. Here, we combine published mouse striatal single-cell datasets from both embryonic and postnatal timepoints to analyze the developmental trajectory patterns and transcription factor regulatory networks within striatal cell types. Using this integrated dataset, we found that dopamine receptor-1 …

Cfp1 Governs Uterine Epigenetic Landscapes To Intervene In Progesterone Responses For Uterine Physiology And Suppression Of Endometriosis, Seung Chel Yang, Mira Park, Kwon-Ho Hong, Hyeonwoo La, Chanhyeok Park, Peike Wang, Gaizhen Li, Qionghua Chen, Youngsok Choi, Francesco J Demayo, John P Lydon, David G Skalnik, Hyunjung J Lim, Seok-Ho Hong, So Hee Park, Yeon Sun Kim, Hye-Ryun Kim, Haengseok Song

Faculty, Staff and Students Publications

Progesterone (P4) is required for the preparation of the endometrium for a successful pregnancy. P4 resistance is a leading cause of the pathogenesis of endometrial disorders like endometriosis, often leading to infertility; however, the underlying epigenetic cause remains unclear. Here we demonstrate that CFP1, a regulator of H3K4me3, is required for maintaining epigenetic landscapes of P4-progesterone receptor (PGR) signaling networks in the mouse uterus. Cfp1f/f;Pgr-Cre (Cfp1d/d) mice showed impaired P4 responses, leading to complete failure of embryo implantation. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 regulates uterine mRNA profiles not only in H3K4me3-dependent …

The Dome Technique For Managing Massive Anterosuperior Medial Acetabular Bone Loss In Revision Total Hip Arthroplasty: Short-Term Outcomes, Tyler J. Humphrey, Colin M. Baker, P. M. Courtney, Wayne G. Paprosky, Hany S. Bedair, Neil P. Sheth, Christopher M. Melnic

Rothman Institute Papers

PURPOSE: The dome technique is a technique used in performance of revision total hip arthroplasty (THA) involving intraoperative joining of two porous metal acetabular augments to fill a massive anterosuperior medial acetabular bone defect. While excellent outcomes were achieved using this surgical technique in a series of three cases, short-term results have not been reported. We hypothesized that excellent short-term clinical and patient reported outcomes could be achieved with use of the dome technique.

MATERIALS AND METHODS: A multicenter case series was conducted for evaluation of patients who underwent revision THA using the dome technique for management of Paprosky 3B …

Real-World Utilization Of The Pill-In-The-Pocket Method For Terminating Episodes Of Atrial Fibrillation: Data From The Multinational Antiarrhythmic Interventions For Managing Atrial Fibrillation (Aim-Af) Survey, James A Reiffel, Carina Blomström-Lundqvist, Giuseppe Boriani, Andreas Goette, Peter R Kowey, Jose L Merino, Jonathan P Piccini, Sanjeev Saksena, A John Camm

Department of Medicine Faculty Papers

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated.

METHODS …

Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria

Kimmel Cancer Center Faculty Papers

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity …

Evaluating The Use Of Blood Pressure Polygenic Risk Scores Across Race/Ethnic Background Groups, Nuzulul Kurniansyah, Matthew O Goodman, Alyna T Khan, Jiongming Wang, Elena Feofanova, Joshua C Bis, Kerri L Wiggins, Jennifer E Huffman, Tanika Kelly, Tali Elfassy, Xiuqing Guo, Walter Palmas, Henry J Lin, Shih-Jen Hwang, Yan Gao, Kendra Young, Gregory L Kinney, Jennifer A Smith, Bing Yu, Simin Liu, Sylvia Wassertheil-Smoller, Joann E Manson, Xiaofeng Zhu, Yii-Der Ida Chen, I-Te Lee, C Charles Gu, Donald M Lloyd-Jones, Sebastian Zöllner, Myriam Fornage, Charles Kooperberg, Adolfo Correa, Bruce M Psaty, Donna K Arnett, Carmen R Isasi, Stephen S Rich, Robert C Kaplan, Susan Redline, Braxton D Mitchell, Nora Franceschini, Daniel Levy, Jerome I Rotter, Alanna C Morrison, Tamar Sofer

Faculty, Staff and Student Publications

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs …

Using Medicare Claims To Estimate Risk-Adjusted Performance Of Pennsylvania Trauma Centers, Alexis M Zebrowski, Phillipe Loher, David G Buckler, Isidore Rigoutsos, Brendan G Carr, Douglas J Wiebe

Computational Medicine Center Faculty Papers

Trauma centers use registry data to benchmark performance using a standardized risk adjustment model. Our objective was to utilize national claims to develop a risk adjustment model applicable across all hospitals, regardless of designation or registry participation. Patients from 2013-14 Pennsylvania Trauma Outcomes Study (PTOS) registry data were probabilistically matched to Medicare claims using demographic and injury characteristics. Pairwise comparisons established facility linkages and matching was then repeated within facilities to link records. Registry models were estimated using GLM and compared with five claims-based LASSO models: demographics, clinical characteristics, diagnosis codes, procedures codes, and combined demographics/clinical characteristics. Area under the …

Curated And Harmonized Gut Microbiome 16s Rrna Amplicon Data From Dietary Fiber Intervention Studies In Humans, Cynthia I Rodriguez, Ali Keshavarzian, Bruce R Hamaker, Feitong Liu, Genelle R Lunken, Heather Rasmussen, Hongwei Zhou, Julien Tap, Kelly S Swanson, Maria Ukhanova, Marion Leclerc, Martin Gotteland, Paola Navarrete, Petia Kovatcheva-Datchary, Wendy J Dahl, Jennifer B H Martiny

Faculty, Staff and Student Publications

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide …

Long-Term Outcomes Of Bevacizumab And Chemoradiation For Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial, Nancy Y. Lee, Jonathan Harris, John Kim, Adam Garden, James Mechalakos, David G. Pfister, Anthony T.C. Chan, Kenneth Hu, A. Dimitrios Colevas, Steven Frank, George Shenouda, Voichita Bar-Ad, John N. Waldron, Paul M. Harari, Adam Raben, Pedro Torres-Saavedra, Quynh-Thu Le

Department of Radiation Oncology Faculty Papers

IMPORTANCE: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

OBJECTIVE: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC.

DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. …

Association Of Circulating Markers With Cognitive Decline After Radiation Therapy For Brain Metastasis, Kristin Huntoon, S Keith Anderson, Karla V Ballman, Erin Twohy, Katharine Dooley, Wen Jiang, Yi An, Jing Li, Christina Von Roemeling, Yaqing Qie, Owen A Ross, Jane H Cerhan, Anthony C Whitton, Jeffrey N Greenspoon, Ian F Parney, Jonathan B Ashman, Jean-Paul Bahary, Constantinos Hadjipanayis, James J Urbanic, Elana Farace, Deepak Khuntia, Nadia N Laack, Paul D Brown, David Roberge, Betty Y S Kim

Faculty, Staff and Student Publications

BACKGROUND: A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline.

METHODS: In this retrospective analysis of prospectively collected …

Machine Learning Reveals Lipidome Remodeling Dynamics In A Mouse Model Of Ovarian Cancer, Olatomiwa O Bifarin, Samyukta Sah, David A Gaul, Samuel G Moore, Ruihong Chen, Murugesan Palaniappan, Jaeyeon Kim, Martin M Matzuk, Facundo M Fernández

Faculty, Staff and Students Publications

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. …

Genome-Wide Coancestry Reveals Details Of Ancient And Recent Male-Driven Reticulation In Baboons, Erik F Sørensen, R Alan Harris, Liye Zhang, Muthuswamy Raveendran, Lukas F K Kuderna, Jerilyn A Walker, Jessica M Storer, Martin Kuhlwilm, Claudia Fontsere, Lakshmi Seshadri, Christina M Bergey, Andrew S Burrell, Juraj Bergman, Jane E Phillips-Conroy, Fekadu Shiferaw, Kenneth L Chiou, Idrissa S Chuma, Julius D Keyyu, Julia Fischer, Marie-Claude Gingras, Sejal Salvi, Harshavardhan Doddapaneni, Mikkel H Schierup, Mark A Batzer, Clifford J Jolly, Sascha Knauf, Dietmar Zinner, Kyle K-H Farh, Tomas Marques-Bonet, Kasper Munch, Christian Roos, Jeffrey Rogers

Faculty, Staff and Students Publications

Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and …

Rare Penetrant Mutations Confer Severe Risk Of Common Diseases, Petko P Fiziev, Jeremy Mcrae, Jacob C Ulirsch, Jacqueline S Dron, Tobias Hamp, Yanshen Yang, Pierrick Wainschtein, Zijian Ni, Joshua G Schraiber, Hong Gao, Dylan Cable, Yair Field, Francois Aguet, Marc Fasnacht, Ahmed Metwally, Jeffrey Rogers, Tomas Marques-Bonet, Heidi L Rehm, Anne O'Donnell-Luria, Amit V Khera, Kyle Kai-How Farh

Faculty, Staff and Students Publications

We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ~10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared …

A Global Catalog Of Whole-Genome Diversity From 233 Primate Species\, Lukas F K Kuderna, Hong Gao, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Thomas Bataillon, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rousselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idrissa S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Joshua G Schraiber, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi, Malu Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda D Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Jeffrey Rogers, Kyle Kai-How Farh, Tomas Marques Bonet

Faculty, Staff and Students Publications

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families …

Phylogenomic Analyses Provide Insights Into Primate Evolution, Yong Shao, Long Zhou, Fang Li, Lan Zhao, Bao-Lin Zhang, Feng Shao, Jia-Wei Chen, Chun-Yan Chen, Xupeng Bi, Xiao-Lin Zhuang, Hong-Liang Zhu, Jiang Hu, Zongyi Sun, Xin Li, Depeng Wang, Iker Rivas-González, Sheng Wang, Yun-Mei Wang, Wu Chen, Gang Li, Hui-Meng Lu, Yang Liu, Lukas F K Kuderna, Kyle Kai-How Farh, Peng-Fei Fan, Li Yu, Ming Li, Zhi-Jin Liu, George P Tiley, Anne D Yoder, Christian Roos, Takashi Hayakawa, Tomas Marques-Bonet, Jeffrey Rogers, Peter D Stenson, David N Cooper, Mikkel Heide Schierup, Yong-Gang Yao, Ya-Ping Zhang, Wen Wang, Xiao-Guang Qi, Guojie Zhang, Dong-Dong Wu

Faculty, Staff and Students Publications

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our …

The Landscape Of Tolerated Genetic Variation In Humans And Primates, Hong Gao, Tobias Hamp, Jeffrey Ede, Joshua G Schraiber, Jeremy Mcrae, Moriel Singer-Berk, Yanshen Yang, Anastasia S D Dietrich, Petko P Fiziev, Lukas F K Kuderna, Laksshman Sundaram, Yibing Wu, Aashish Adhikari, Yair Field, Chen Chen, Serafim Batzoglou, Francois Aguet, Gabrielle Lemire, Rebecca Reimers, Daniel Balick, Mareike C Janiak, Martin Kuhlwilm, Joseph D Orkin, Shivakumara Manu, Alejandro Valenzuela, Juraj Bergman, Marjolaine Rousselle, Felipe Ennes Silva, Lidia Agueda, Julie Blanc, Marta Gut, Dorien De Vries, Ian Goodhead, R Alan Harris, Muthuswamy Raveendran, Axel Jensen, Idriss S Chuma, Julie E Horvath, Christina Hvilsom, David Juan, Peter Frandsen, Fabiano R De Melo, Fabrício Bertuol, Hazel Byrne, Iracilda Sampaio, Izeni Farias, João Valsecchi Do Amaral, Mariluce Messias, Maria N F Da Silva, Mihir Trivedi, Rogerio Rossi, Tomas Hrbek, Nicole Andriaholinirina, Clément J Rabarivola, Alphonse Zaramody, Clifford J Jolly, Jane Phillips-Conroy, Gregory Wilkerson, Christian Abee, Joe H Simmons, Eduardo Fernandez-Duque, Sree Kanthaswamy, Fekadu Shiferaw, Dongdong Wu, Long Zhou, Yong Shao, Guojie Zhang, Julius D Keyyu, Sascha Knauf, Minh D Le, Esther Lizano, Stefan Merker, Arcadi Navarro, Thomas Bataillon, Tilo Nadler, Chiea Chuen Khor, Jessica Lee, Patrick Tan, Weng Khong Lim, Andrew C Kitchener, Dietmar Zinner, Ivo Gut, Amanda Melin, Katerina Guschanski, Mikkel Heide Schierup, Robin M D Beck, Govindhaswamy Umapathy, Christian Roos, Jean P Boubli, Monkol Lek, Shamil Sunyaev, Anne O'Donnell-Luria, Heidi L Rehm, Jinbo Xu, Jeffrey Rogers, Tomas Marques-Bonet, Kyle Kai-How Farh

Faculty, Staff and Students Publications

INTRODUCTION:

Millions of people have received genome and exome sequencing to date, a collective effort that has illuminated for the first time the vast catalog of small genetic differences that distinguish us as individuals within our species. However, the effects of most of these genetic variants remain unknown, limiting their clinical utility and actionability. New approaches that can accurately discern disease-causing from benign mutations and interpret genetic variants on a genome-wide scale would constitute a meaningful initial step towards realizing the potential of personalized genomic medicine.

RATIONALE:

As a result of the short evolutionary distance between humans and nonhuman primates, …

Radiologic And Histologic Findings Of Locally Advanced Mucoepidermoid Carcinoma Managed With Total Surgical Excision, Christopher R. Huber, Don Truong, Joseph Hatem, Joel Thompson, Bryan Scott

Advances in Clinical Medical Research and Healthcare Delivery

The present case report provides images from computed tomography and histology of a patient with a salivary gland neoplasm consistent with mucoepidermoid carcinoma.

Comparing Pleural Fluid Removal Volume And Oxygenation Change In Therapeutic Thoracentesis: Is There A Relationship?, Hannah Zazulak, Ryanne Burke, Andrea Bodine

Advances in Clinical Medical Research and Healthcare Delivery

Background: During therapeutic thoracentesis (TT), pleural fluid is typically drained to completion. Fluid removal improves oxygenation, and the amount of fluid removed is directly associated with the risk of serious complications. A relationship between the amount of fluid removed during TT and the change in oxygenation has not been found in the literature. A direct relationship was hypothesized in this study. Differences in the change in oxygenation between sexes, age, and pre-procedure oxygen support were secondarily hypothesized. This information would assist in the guidance of future TT protocols.

Methods: Subjects of this retrospective cohort study were males and females aged …

Late-Onset Isolated Myositis Following Transobturator Mid-Urethral Sling: A Case Report, Bruce Lee, Mohamad Mahmoud

Advances in Clinical Medical Research and Healthcare Delivery

Late onset of isolated myositis following a Transobturator (TOT) mid-urethral sling (MUS) is a rare post-operative complication.

A 38-year-old gravida 3 para 3003 with a long standing history of mixed urinary incontinence, Stage 2 anterior prolapse, dysmenorrhea, and abnormal uterine bleeding underwent a hysteroscopy with dilation and curettage, levonorgestrel intrauterine device insertion, anterior colporrhaphy, MUS insertion using the TOT approach and cystoscopy. Eight weeks post-op, she presented to the emergency room with right inguinal and low back pain, difficulty ambulating, and fevers. Magnetic Resonance Imaging (MRI) of the right hip revealed inflammatory fluid collection within the adductor brevis with posterior …

Covid-19 Vaccination Hesitancy In Pregnancy: A Retrospective Cohort Study Of Patients’ Perceptions, Molly Schassberger, Charlotte Kirk, Samantha Fields, Carol Brenner, Andrea M. Bodine Md

Advances in Clinical Medical Research and Healthcare Delivery

COVID-19 Vaccination Hesitancy in Pregnancy: A Retrospective Cohort Study of Patients’ Perceptions

Schassberger¹, M, MS III, Kirk¹, C, MS III, Fields¹, S, MS III, Brenner¹, C, Ph.D., Bodine², A, M.D.

¹University of New England College of Osteopathic Medicine, Biddeford, Maine

²Berkshire Medical Center, Pittsfield, Massachusetts

Introduction: The COVID-19 vaccination rate of US pregnant individuals of childbearing age was 42.3%, compared to 63.7% of the total population as of 1/15/2022 despite ACOG and CDC recommendations. Our objectives were to determine patients’ perceptions on COVID-19 vaccine safety and efficacy …

Rare Case Of Late-Onset Myasthenia Gravis In A 65-Year-Old Female With Prolonged Doxycycline Use, Angel Wong, Kayvan Mirhadi

Advances in Clinical Medical Research and Healthcare Delivery

Myasthenia gravis (MG) is a rare autoimmune condition caused by antibody-mediated disruption of acetylcholine receptors (AChR) or their associated proteins. The age of onset of MG has a bimodal distribution, with a predominance of female cases in the second and third decades and a predominance of male cases in the sixth to eighth decades. MG is often unmasked by stressors such as systemic illness, medication, surgery, and pregnancy. We present a case of late-onset MG in a 65-year-old female with a recent history of prolonged doxycycline use. However, there are aspects of her past medical history, including comorbidities involving the …

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …

Journal Club: Glymphatic System In Neurodegenerative Diseases, Ronald G. Lott Iii, Xavier Zonna, Samuel Wlasowicz

Advances in Clinical Medical Research and Healthcare Delivery

Neurodegenerative diseases such as Alzheimer's Disease impact a multitude of individuals worldwide. The neural Glymphatic system is a relatively newly discovered cellular transport pathway within the brain that has been implicated in neurodegenerative diseases. This article serves to provide a journal club review of current literature on the Glymphatic system to raise awareness of this system and its potential for future treatment and prevention of neurodegenerative conditions.

The Effects Of Synovial Fluid And Inflammatory Cells On Orthopaedic Implant Alloys, Lisa Phan

Theses and Dissertations (ETD)

Introduction. Total knee arthroplasty (TKA) is a common surgical procedure used to treat end-stage osteoarthritis. The implants used in TKA typically consist of a Cobalt Chromium Molybdenum (CoCrMo) femoral component and a Titanium Aluminum Vanadium (TiAlV) alloy baseplate. These metal alloys are chosen for their mechanical properties, corrosion resistance, high affinity for bone, and biocompatibility. However, they can be susceptible to mechanical and electrochemical wear, leading to the release of metal ions. Osteoarthritis and inflammation can alter the composition of Synovial Fluid (SF), potentially causing implant corrosion and the release of metal ions into the surrounding tissue. These metal ions …

A Seven-Year Review Of Hospital- Onset Clostridioides Difficile Infection Reduction And The Case For A Multidisciplinary Taskforce Approach, Peggy Brown Mph, Cic, Michelle Charles Msn, Rn-Bc, Brittany S. Thorp Mph, Kristin Sims Mph Cic Cpps Fapic, R. Scott Stienecker Md

Infection Control

Presented at the 2023 APIC Annual Conference

Background: Hospital-onset Clostridioides difficile infection is a life-threatening disease that can prolong and complicate a patient's hospitalization. To reduce HO-CDIs and ensure positive health outcomes with reduced cost, utilization of a multi-disciplinary taskforce (MDT) is key to identify gaps, develop action plans, and implement and review interventions in the most efficient and effective manner.

Methods: Over the course of seven years, two rounds of interventions were executed consecutively across a nine-hospital healthcare system to reduce HO-CDI events. The first round (Round 1) driven solely by the Infection Prevention (IP) department spanned four years …

Candida Auris Screening In The Acute Care Setting: An Infection Control Partnership Between Hospitals And Skilled Nursing Facilities, Brittany S. Thorp Mph, Peggy Brown Mph, Cic, R. Scott Stienecker Md

Infection Control

Presented at 2023 APIC Annual Conference

Background: Candida auris (C. auris) is a drug-resistant fungus that can spread easily between hospitalized patients and nursing home residents. To mitigate risk of C. auris spread, a nine-hospital healthcare system developed a C. auris screening tool in January 2020. Infection Preventionists (IPs) use the screening tool to determine which patients qualify for C. auris screening, looking specifically at the facility type where the patient came from. The IP then initiates the isolation and testing protocol with the bedside nurse and provider.

Methods: Over the course of three years, the hospital epidemiologist collected data …