Medical Specialties Commons^™

Poziotinib Inhibits Her2-Mutant-Driven Therapeutic Resistance And Multiorgan Metastasis In Breast Cancer, Rashi Kalra, Ching Hui Chen, Junkai Wang, Ahmad Bin Salam, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Clayton C Yates, Carolina Gutierrez, Balasubramanyam Karanam, Meenakshi Anurag, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan …

Secure Human Action Recognition By Encrypted Neural Network Inference, Miran Kim, Xiaoqian Jiang, Kristin Lauter, Elkhan Ismayilzada, Shayan Shams

Faculty, Staff and Student Publications

Advanced computer vision technology can provide near real-time home monitoring to support "aging in place" by detecting falls and symptoms related to seizures and stroke. Affordable webcams, together with cloud computing services (to run machine learning algorithms), can potentially bring significant social benefits. However, it has not been deployed in practice because of privacy concerns. In this paper, we propose a strategy that uses homomorphic encryption to resolve this dilemma, which guarantees information confidentiality while retaining action detection. Our protocol for secure inference can distinguish falls from activities of daily living with 86.21% sensitivity and 99.14% specificity, with an average …

A Multi-Institutional Prediction Model To Estimate The Risk Of Recurrence And Mortality After Mastectomy For T1-2n1 Breast Cancer, Sarah M C Sittenfeld, Emily C Zabor, Sarah N Hamilton, Henry M Kuerer, Mahmoud El-Tamer, George E Naoum, Pauline T Truong, Alan Nichol, Benjamin D Smith, Wendy A Woodward, Tracy-Ann Moo, Simon N Powell, Chirag S Shah, Alphonse G Taghian, Ibrahim Abu-Gheida, Rahul D Tendulkar

Faculty, Staff and Student Publications

Background: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial.

Methods: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM).

Results: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more …

Good Scientific Practice In Eeg And Meg Research: Progress And Perspectives, Guiomar Niso, Laurens R Krol, Etienne Combrisson, A Sophie Dubarry, Madison A Elliott, Clément François, Yseult Héjja-Brichard, Sophie K Herbst, Karim Jerbi, Vanja Kovic, Katia Lehongre, Steven J Luck, Manuel Mercier, John C Mosher, Yuri G Pavlov, Aina Puce, Antonio Schettino, Daniele Schön, Walter Sinnott-Armstrong, Bertille Somon, Anđela Šoškić, Suzy J Styles, Roni Tibon, Martina G Vilas, Marijn Van Vliet, Maximilien Chaumon

Faculty, Staff and Student Publications

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical …

Gray And White Matter Abnormality In Patients With T2dm-Related Cognitive Dysfunction: A Systemic Review And Meta-Analysis, Teng Ma, Ze-Yang Li, Ying Yu, Bo Hu, Yu Han, Min-Hua Ni, Yu-Xiang Huang, Hao-Han Chen, Wen Wang, Lin-Feng Yan, Guang-Bin Cui

Faculty, Staff and Student Publications

Aims/hypothesis

Brain structure abnormality in patients with type 2 diabetes mellitus (T2DM)-related cognitive dysfunction (T2DM-CD) has been reported for decades in magnetic resonance imaging (MRI) studies. However, the reliable results were still unclear. This study aimed to make a systemic review and meta-analysis to find the significant and consistent gray matter (GM) and white matter (WM) alterations in patients with T2DM-CD by comparing with the healthy controls (HCs).

Methods

Published studies were systemically searched from PubMed, MEDLINE, Cochrane Library and Web of Science databases updated to November 14, 2021. Studies reporting abnormal GM or WM between patients with T2DM-CD and …

Genetic Variants In Cyp2b6 And Hsd17b12 Associated With Risk Of Squamous Cell Carcinoma Of The Head And Neck, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Kristina R Dahlstrom, Mulong Du, Christopher I Amos, David C Christiani, Philip Lazarus, Qingyi Wei

Faculty, Staff and Students Publications

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

Standardizing Evaluation Of Patient-Specific 3d Printed Models In Surgical Planning: Development Of A Cross-Disciplinary Survey Tool For Physician And Trainee Feedback, Lauren Schlegel, Michelle Ho, M. Fields, Erik Backlund, Robert S. Pugliese, Kristy M. Shine

Department of Emergency Medicine Faculty Papers

Background: 3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning.

Methods: A literature review was conducted to identify survey questions administered to clinicians in …

Understanding Diagnostic Pathways In Systemic Sclerosis And Systemic Sclerosis-Associated Interstitial Lung Disease: A Retrospective Cohort Study, Shervin Assassi, Nan Shao, Ziwei Yin, Elizabeth R Volkmann, Donald F Zoz, Thomas B Leonard

Faculty, Staff and Student Publications

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optum's Clinformatics® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients …

Improved Sars-Cov-2 Sequencing Surveillance Allows The Identification Of New Variants And Signatures In Infected Patients, Antonio Grimaldi, Francesco Panariello, Patrizia Annunziata, Teresa Giuliano, Michela Daniele, Biancamaria Pierri, Chiara Colantuono, Marcello Salvi, Valentina Bouché, Anna Manfredi, Maria Concetta Cuomo, Denise Di Concilio, Claudia Tiberio, Mariano Fiorenza, Giuseppe Portella, Ilaria Cimmino, Antonio Sorrentino, Giovanna Fusco, Maria Rosaria Granata, Pellegrino Cerino, Antonio Limone, Luigi Atripaldi, Andrea Ballabio, Davide Cacchiarelli

Duncan NRI Faculty and Staff Publications

Background: Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies or previous virus exposure. It is also becoming clear now that efficient genomic surveillance would require monitoring of the host gene expression to identify prognostic biomarkers of treatment efficacy and disease progression. Here we propose an integrative workflow to both generate thousands of SARS-CoV-2 genome sequences per week and analyze host …

Risk Of Transmission Of Respiratory Viruses During Aerosol-Generating Medical Procedures (Agmps) Revisited In The Covid-19 Pandemic: A Systematic Review, Jenine Leal, Brenlea Farkas, Liza Mastikhina, Jordyn Flanagan, Becky Skidmore, Charleen Salmon, Devika Dixit, Stephanie Smith, Stephen Tsekrekos, Bonita Lee, Joseph Vayalumkal, Jessica Dunn, Robyn Harrison, Melody Cordoviz, Roberta Dubois, Uma Chandran, Fiona Clement, Kathryn Bush, John Conly, Oscar Larios

Faculty, Staff and Student Publications

BACKGROUND: In many jurisdictions healthcare workers (HCWs) are using respirators for aerosol-generating medical procedures (AGMPs) performed on adult and pediatric populations with all suspect/confirmed viral respiratory infections (VRIs). This systematic review assessed the risk of VRIs to HCWs in the presence of AGMPs, the role respirators versus medical/surgical masks have on reducing that risk, and if the risk to HCWs during AGMPs differed when caring for adult or pediatric patient populations.

MAIN TEXT: We searched MEDLINE, EMBASE, Cochrane Central, Cochrane SR, CINAHL, COVID-19 specific resources, and MedRxiv for English and French articles from database inception to September 9, 2021. Independent …

A Comprehensive Search Of Non-Canonical Proteins In Non-Small Cell Lung Cancer And Their Impact On The Immune Response, Ehsan Irajizad, Johannes F Fahrmann, James P Long, Jody Vykoukal, Makoto Kobayashi, Michela Capello, Chuan-Yih Yu, Yining Cai, Fu Chung Hsiao, Nikul Patel, Soyoung Park, Qian Peng, Jennifer B Dennison, Taketo Kato, Mei Chee Tai, Ayumu Taguchi, Humam Kadara, Ignacio I Wistuba, Hiroyuki Katayama, Kim-Anh Do, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess …

Increased Expression Of Interferon-Induced Transmembrane 3 (Ifitm3) In Stroke And Other Inflammatory Conditions In The Brain, Elisabeth Harmon, Andrea Doan, Jesus Bautista-Garrido, Joo Eun Jung, Sean P Marrelli, Gab Seok Kim

Faculty, Staff and Student Publications

Microglia, the resident innate immune cells of the brain, become more highly reactive with aging and diseased conditions. In collaboration with other cell types in brains, microglia can contribute both to worsened outcome following stroke or other neurodegenerative diseases and to the recovery process by changing their phenotype toward reparative microglia. Recently, IFITM3 (a member of the "interferon-inducible transmembrane" family) has been revealed as a molecular mediator between amyloid pathology and neuroinflammation. Expression of IFITM3 in glial cells, especially microglia following stroke, is not well described. Here, we present evidence that ischemic stroke causes an increase in IFITM3 expression along …

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …

A Qualitative Exploration Of The Functional, Social, And Emotional Impacts Of The Covid-19 Pandemic On People Who Use Drugs, Erin L Kelly, Megan K Reed, Kathryn M Schoenauer, Kelsey Smith, Kristina Scalia-Jackson, Sequoia Kay Hill, Erica Li, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

Since 2020, people who use drugs (PWUD) experienced heightened risks related to drug supply disruptions, contamination, overdose, social isolation, and increased stress. This study explored how the lives of PWUD changed in Philadelphia over a one-year period. Using semi-structured interviews with 20 participants in a Housing First, low-barrier medication for opioid use (MOUD) program in Philadelphia, the effects of the first year of the COVID-19 pandemic on the daily lives, resources, functioning, substance use, and treatment of PWUD were explored. Interviews were analyzed using a combination of directed and conventional content analysis. Six overarching themes emerged during data analysis: (1) …

The Hearst Health Prize: The First Five Years, Alexa M. Waters, Alexis Skoufalos, Emily Frelick, Gregory Dorn, David B. Nash

Department of Family & Community Medicine Faculty Papers

The Hearst Health Prize is the first national annual award for excellence in population health. The prize was established "to discover, support, and showcase the work of an individual, group, organization, or institution that has successfully implemented a population health program or intervention that has made a measurable difference" in health outcomes. Now, 5 years since the award's inception, this article reflects on how submissions for the prize collectively mirror - and may even predict - changes within the field of population health. It examines how the most successful programs demonstrated genuine, measurable improvements in health outcomes and/or health behaviors. …

Qualitative Interviews To Understand Health Care Providers’ Experiences Of Prescribing Licensed Peanut Oral Immunotherapy, Aikaterini Anagnostou, Claire Lawrence, Stephen A Tilles, Susan Laubach, Sarah M Donelson, Mohamed Yassine, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

OBJECTIVE: This research sought to explore health care providers' (HCPs) experiences of delivering the first US Food and Drug Administration (FDA) and European Commission (EC) approved peanut oral immunotherapy (peanut OIT; Palforzia). Semi-structured qualitative interviews with HCPs who had initiated treatment with ≥ 3 patients in the first nine months following FDA approval sought to identify challenges faced and successful implementation strategies.

RESULTS: Eight allergists and three nurse practitioners from eight sites based in the United States participated. The HCPs included in this research were motivated to implement this novel treatment, however, entered the process with some reservations. HCPs described …

The Value Of In Vivo Reflectance Confocal Microscopy As An Assessment Tool In Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study, Sabrina R Ramnarine, Patrick M Dougherty, Roman Rolke, Linda J Williams, Christi Alessi-Fox, Andrew J Coleman, Caterina Longo, Lesley A Colvin, Marie T Fallon

Faculty, Staff and Student Publications

Background: There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner's corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN.

Patients and methods: Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical …

Genetic Variants In Aldh1l1 And Gldc Influence The Serine-To-Glycine Ratio In Hispanic Children, Sergey A Krupenko, Shelley A Cole, Ruixue Hou, Karin Haack, Sandra Laston, Nitesh R Mehta, Anthony G Comuzzie, Nancy F Butte, V Saroja Voruganti

Children’s Nutrition Research Center Staff Publications

Background: Glycine is a proteogenic amino acid that is required for numerous metabolic pathways, including purine, creatine, heme, and glutathione biosynthesis. Glycine formation from serine, catalyzed by serine hydroxy methyltransferase, is the major source of this amino acid in humans. Our previous studies in a mouse model have shown a crucial role for the 10-formyltetrahydrofolate dehydrogenase enzyme in serine-to-glycine conversion.

Objectives: We sought to determine the genomic influence on the serine-glycine ratio in 803 Hispanic children from 319 families of the Viva La Familia cohort.

Methods: We performed a genome-wide association analysis for plasma serine, glycine, and the serine-glycine ratio …

Risk Assessment With Low-Pass Whole-Genome Sequencing Of Cell-Free Dna Before Cd19 Car T-Cell Therapy For Large B-Cell Lymphoma, Hua-Jay J Cherng, Ryan Sun, Bryant Sugg, Russell Irwin, Haopeng Yang, Cao Cuong Le, Qing Deng, Luis Fayad, Nathan H Fowler, Simrit Parmar, Raphael Steiner, Fredrick Hagemeister, Ranjit Nair, Hun Ju Lee, Maria Rodriguez, Felipe Samaniego, Swaminathan P Iyer, Christopher R Flowers, Linghua Wang, Loretta J Nastoupil, Sattva S Neelapu, Sairah Ahmed, Paolo Strati, Michael R Green, Jason Westin

Faculty, Staff and Student Publications

Patients with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART19). However, more than half of recipients will experience treatment failure. Thus, approaches are needed to identify high-risk patients who may benefit from alternative or consolidative therapy. We evaluated low-pass whole-genome sequencing (lpWGS) of cell-free DNA (cfDNA) before CART19 as a new approach for risk stratification. We performed lpWGS on pretreatment plasma samples from 122 patients at time of leukapheresis who received standard-of-care CART19 for rrLBCL to define DNA copy number alterations (CNAs). In multivariable selection, high focal CNA score …

Primary Cutaneous Lymphoma: Recommendations For Clinical Trial Design And Staging Update From The Iscl, Usclc, And Eortc, Elise A Olsen, Sean Whittaker, Rein Willemze, Lauren Pinter-Brown, Francine Foss, Larisa Geskin, Lawrence Schwartz, Steven Horwitz, Joan Guitart, John Zic, Youn H Kim, Gary S Wood, Madeleine Duvic, Wei Ai, Michael Girardi, Alejandro Gru, Emmanuella Guenova, Emmilia Hodak, Richard Hoppe, Werner Kempf, Ellen Kim, Mary Jo Lechowicz, Pablo Ortiz-Romero, Evangelia Papadavid, Pietro Quaglino, Mark Pittelkow, H Miles Prince, Jose Antonio Sanches, Makoto Sugaya, Maarten Vermeer, Jasmine Zain, Robert Knobler, Rudolf Stadler, Martine Bagot, Julia Scarisbrick

Faculty, Staff and Student Publications

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), …

Tale Of Two Cities: Narrative Review Of Oxygen, Sung-Ho Ahn, Angela Burkett, Atzhiry Paz, Jude P Savarraj, Sarah Hinds, Georgene Hergenroeder, Aaron M Gusdon, Xuefeng Ren, Jeong-Ho Hong, Huimahn A Choi

Faculty, Staff and Student Publications

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.

METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early …

Microenvironmental Landscape Of Human Melanoma Brain Metastases In Response To Immune Checkpoint Inhibition, Christopher Alvarez-Breckenridge, Samuel C Markson, Jackson H Stocking, Naema Nayyar, Matt Lastrapes, Matthew R Strickland, Albert E Kim, Magali De Sauvage, Ashish Dahal, Juliana M Larson, Joana L Mora, Andrew W Navia, Robert H Klein, Benjamin M Kuter, Corey M Gill, Mia Bertalan, Brian Shaw, Alexander Kaplan, Megha Subramanian, Aarushi Jain, Swaminathan Kumar, Husain Danish, Michael White, Osmaan Shahid, Kristen E Pauken, Brian C Miller, Dennie T Frederick, Christine Hebert, Mckenzie Shaw, Maria Martinez-Lage, Matthew Frosch, Nancy Wang, Elizabeth Gerstner, Brian V Nahed, William T Curry, Bob Carter, Daniel P Cahill, Genevieve Marie Boland, Benjamin Izar, Michael A Davies, Arlene H Sharpe, Mario L Suvà, Ryan J Sullivan, Priscilla K Brastianos, Scott L Carter

Faculty, Staff and Student Publications

Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM …

Association Between Social Vulnerability Index And Cardiovascular Disease: A Behavioral Risk Factor Surveillance System Study, Vardhmaan Jain, Mahmoud Al Rifai, Safi U Khan, Ankur Kalra, Fatima Rodriguez, Zainab Samad, Yashashwi Pokharel, Arunima Misra, Laurence S Sperling, Jamal S Rana, Waqas Ullah, Ankit Medhekar, Salim S Virani

Division of Cardiology Faculty Papers

Background Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and …

Polygenic Risk, Midlife Life's Simple 7, And Lifetime Risk Of Stroke, Emy A Thomas, Nitesh Enduru, Adrienne Tin, Eric Boerwinkle, Michael E Griswold, Thomas H Mosley, Rebecca F Gottesman, Myriam Fornage

Faculty, Staff and Student Publications

Background

Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke.

Methods and Results

Study participants were 11 568 middle‐aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels …

Muscle And Adipose Tissue Segmentations At The Third Cervical Vertebral Level In Patients With Head And Neck Cancer, Kareem A Wahid, Brennan Olson, Rishab Jain, Aaron J Grossberg, Dina El-Habashy, Cem Dede, Vivian Salama, Moamen Abobakr, Abdallah S R Mohamed, Renjie He, Joel Jaskari, Jaakko Sahlsten, Kimmo Kaski, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

The accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, a set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was …

Association Between Social Vulnerability Index And Cardiovascular Disease: A Behavioral Risk Factor Surveillance System Study, Vardhmaan Jain, Mahmoud Al Rifai, Safi U Khan, Ankur Kalra, Fatima Rodriguez, Zainab Samad, Yashashwi Pokharel, Arunima Misra, Laurence S Sperling, Jamal S Rana, Waqas Ullah, Ankit Medhekar, Salim S Virani

Faculty, Staff and Students Publications

Background Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and …

Synchronized Diaphragmatic Stimulation For Heart Failure Using The Visone System: A First-In-Patient Study., Ana Jorbendaze, Robin Young, Tamaz Shaburishvili, Vitaly Demyanchuk, Roman Buriak, Borys Todurov, Kostyantyn Rudenko, Michel Zuber, Simon F Stämpfli, Felix C Tanner, Paul Erne, Michael Mirro Md, Facc, Fhrs, Faha, Marat Fudim, Lee R Goldberg, John G F Cleland

Parkview Heart Institute

AIMS: Synchronized diaphragmatic stimulation (SDS) modulates intrathoracic and intra-abdominal pressures with favourable effects on cardiac function for patients with a reduced left ventricular ejection fraction (LVEF) and heart failure (HFrEF). VisONE-HF is a first-in-patient, observational study assessing the feasibility and 1 year effects of a novel, minimally invasive SDS device.

METHODS AND RESULTS: The SDS system comprises a pulse generator and two laparoscopically delivered, bipolar, active-fixation leads on the inferior diaphragmatic surface. Fifteen symptomatic men with HFrEF and ischaemic heart disease receiving guideline-recommended therapy were enrolled (age 60 [56, 67] years, New York Heart Association class II [53%] /III [47%], …

Risk Of Alzheimer’S Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching, Avram S Bukhbinder, Yaobin Ling, Omar Hasan, Xiaoqian Jiang, Yejin Kim, Kamal N Phelps, Rosemarie E Schmandt, Albert Amran, Ryan Coburn, Srivathsan Ramesh, Qian Xiao, Paul E Schulz

Faculty, Staff and Student Publications

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized.

OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years …

Structural Plasticity Can Produce Metaplasticity, Wenli Zhao, Shuo Han, Na Qiu, Wenbo Feng, Mengjie Lu, Wenru Zhang, Mu Wang, Qingtong Zhou, Shutian Chen, Wei Xu, Juan Du, Xiaojing Chu, Cuiying Yi, Antao Dai, Liaoyuan Hu, Michelle Y Shen, Yaping Sun, Qing Zhang, Yingli Ma, Wenge Zhong, Dehua Yang, Ming-Wei Wang, Beili Wu, Qiang Zhao

Faculty, Staff and Student Publications

Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of Gi1-bound SSTR2 in the presence of the …