Medical Specialties Commons^™

Disease-Modifying Therapies And Features Linked To Treatment Response In Type 1 Diabetes Prevention: A Systematic Review, Jamie L Felton, Kurt J Griffin, Richard A Oram, Cate Speake, S Alice Long, Suna Onengut-Gumuscu, Stephen S Rich, Gabriela S F Monaco, Carmella Evans-Molina, Linda A Dimeglio, Heba M Ismail, Andrea K Steck, Dana Dabelea, Randi K Johnson, Marzhan Urazbayeva, Stephen Gitelman, John M Wentworth, Maria J Redondo, Emily K Sims, Ada/Easd Pmdi

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.

METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a …

Genomic Variant Benchmark: If You Cannot Measure It, You Cannot Improve It, Sina Majidian, Daniel Paiva Agustinho, Chen-Shan Chin, Fritz J Sedlazeck, Medhat Mahmoud

Faculty, Staff and Students Publications

Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.

Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg

Faculty, Staff and Students Publications

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

METHODS: The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident …

Analysis And Prediction Of Liver Volume Change Maps Derived From Computational Tomography Scans Acquired Pre- And Post-Radiation Therapy, Guillaume Cazoulat, Aashish C Gupta, Mais M Al Taie, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

External beam radiation therapy (EBRT) of liver cancers can cause local liver atrophy as a result of tissue damage or hypertrophy as a result of liver regeneration. Predicting those volumetric changes would enable new strategies for liver function preservation during treatment planning. However, understanding of the spatial dose/volume relationship is still limited. This study leverages the use of deep learning-based segmentation and biomechanical deformable image registration (DIR) to analyze and predict this relationship. Pre- and Post-EBRT imaging data were collected for 100 patients treated for hepatocellular carcinomas, cholangiocarcinoma or CRC with intensity-modulated radiotherapy (IMRT) with prescription doses ranging from 50 …

Detection Of Early Myocardial Dysfunction By Imaging Biomarkers In Cancer Patients Undergoing Photon Beam Vs Proton Beam Radiotherapy: A Prospective Study, Muhannad Aboud Abbasi, Giulia Bruno, Cristina Di Stefano, Laura Garcia Bello, Nadia N Laack, Kimberly S Corbin, Thomas J Whitaker, Patricia A Pellikka, Robert W Mutter, Hector R Villarraga

Faculty, Staff and Student Publications

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) …

The Use Of Electronic Health Record Data To Identify Variation In Referral, Consent, And Engagement In A Pediatric Intervention For Overweight And Obesity: A Cross-Sectional Study, Joshua S Yudkin, Marlyn A Allicock, Folefac D Atem, Carol A Galeener, Sarah E Messiah, Sarah E Barlow

Faculty, Staff and Student Publications

Clinical weight management programs face low participation. The authors assessed whether using electronic health record (EHR) data can identify variation in referral, consent, and engagement in a pediatric overweight and obesity (OW/OB) intervention. Using Epic EHR data collected between August 2020 and April 2021, sociodemographic and clinical diagnostic data (ie, International Classification of Disease [ICD] codes from visit and problem list [PL]) were analyzed to determine their association with referral, consent, and engagement in an OW/OB intervention. Bivariate analyses and multivariable logistic regression modeling were performed, with Bayesian inclusion criterion score used for model selection. Compared with the 581 eligible …

Index Of Consciousness Monitoring During General Anesthesia May Effectively Enhance Rehabilitation In Elderly Patients Undergoing Laparoscopic Urological Surgery: A Randomized Controlled Clinical Trial, Fengling Qi, Long Fan, Chunxiu Wang, Yang Liu, Shuyi Yang, Zhen Fan, Fangfang Miao, Minhui Kan, Kunpeng Feng, Tianlong Wang

Faculty, Staff and Student Publications

Background: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia.

Methods: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group …

Influence Of Sex On Meat And Fat Quality From Heavy Alentejano Pigs Finished Outdoors On Commercial And High Fiber Diets, José Manuel Martins, Rui Charneca, Nicolás Garrido, André Albuquerque, Eliana Jerónimo, Olinda Guerreiro, Patrícia Lage, Carla Marmelo, Filipa Costa, Amélia Ramos, Luísa Martin

Faculty, Staff and Student Publications

This work aimed to examine the effects of sex on meat and fat quality traits from thirty Portuguese Alentejano (AL) pigs reared in outdoor conditions. These pigs were divided into three groups and fed ad libitum. From ~40 to 130 kg LW, castrated (C group) and intact animals (I and IExp) consumed commercial diets. Until slaughter (~160 kg), C and I pigs remained on commercial diets, and IExp changed to a more sustainable experimental diet with locally produced pulses and byproducts. Samples were collected from the Longissimus lumborum (LL), Psoas major (PM), and dorsal subcutaneous fat (DSF). At ~160 …

Gut Microbiota Aggravates Neutrophil Extracellular Traps-Induced Pancreatic Injury In Hypertriglyceridemic Pancreatitis, Guanqun Li, Liwei Liu, Tianqi Lu, Yuhang Sui, Can Zhang, Yongwei Wang, Tao Zhang, Yu Xie, Peng Xiao, Zhongjie Zhao, Chundong Cheng, Jisheng Hu, Hongze Chen, Dongbo Xue, Hua Chen, Gang Wang, Rui Kong, Hongtao Tan, Xuewei Bai, Zhibo Li, Florencia Mcallister, Le Li, Bei Sun

Faculty, Staff and Student Publications

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

Hemizygous Variants In Protein Phosphatase 1 Regulatory Subunit 3f (Ppp1r3f) Are Associated With A Neurodevelopmental Disorder Characterized By Developmental Delay, Intellectual Disability And Autistic Features, Zhigang Liu, Baozhong Xin, Iris N Smith, Valerie Sency, Julia Szekely, Anna Alkelai, Alan Shuldiner, Stephanie Efthymiou, Farrah Rajabi, Stephanie Coury, Catherine A Brownstein, Sabine Rudnik-Schöneborn, Ange-Line Bruel, Julien Thevenon, Shimriet Zeidler, Parul Jayakar, Axel Schmidt, Kirsten Cremer, Hartmut Engels, Sophia O Peters, Maha S Zaki, Ruizhi Duan, Changlian Zhu, Yiran Xu, Chao Gao, Tania Sepulveda-Morales, Reza Maroofian, Issam A Alkhawaja, Mariam Khawaja, Hunaida Alhalasah, Henry Houlden, Jill A Madden, Valentina Turchetti, Dana Marafi, Pankaj B Agrawal, Ulrich Schatz, Ari Rotenberg, Joshua Rotenberg, Grazia M S Mancini, Somayeh Bakhtiari, Michael Kruer, Isabelle Thiffault, Steffen Hirsch, Maja Hempel, Lara G Stühn, Tobias B Haack, Jennifer E Posey, James R Lupski, Hyunpil Lee, Nicholas B Sarn, Charis Eng, Claudia Gonzaga-Jauregui, Bin Zhang, Heng Wang

Faculty, Staff and Students Publications

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males …

Effect Of Preoperative Programmed Death-1 Or Programmed Death Ligand-1 Immune Check Point Inhibition On Complications After Surgery For Primary Head And Neck Cancer, Ramez Philips, Angela Alnemri, Dev Amin, Jena Patel, Michael C. Topf, Jennifer M. Johnson, Voichita Bar-Ad, Rita Axelrod, Athanassios Argiris, Christopher Fundakowski, Adam J. Luginbuhl, David M. Cognetti, Joseph M. Curry

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications.

METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. …

High-Level Ceftazidime/Avibactam Resistance In Escherichia Coli Conferred By The Novel Plasmid-Mediated Β-Lactamase Cmy-185 Variant, William C Shropshire, Bradley T Endres, Jovan Borjan, Samuel L Aitken, William C Bachman, Christi L Mcelheny, Chin-Ting Wu, Stephanie L Egge, Ayesha Khan, William R Miller, Micah M Bhatti, Pranoti Saharasbhojane, Akito Kawai, Ryan K Shields, Samuel A Shelburne, Yohei Doi

Faculty, Staff and Student Publications

OBJECTIVES: To characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.

METHODS: A patient with an intra-abdominal infection due to recurrent E. coli was treated with ceftazidime/avibactam. On Day 48 of ceftazidime/avibactam therapy, E. coli with a ceftazidime/avibactam MIC of >256 mg/L was identified from abdominal drainage. Illumina and Oxford Nanopore Technologies WGS was performed on serial isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for ceftazidime/avibactam resistance.

RESULTS: WGS revealed that all three isolates were E. coli ST410. The ceftazidime/avibactam-resistant strain uniquely …

Bricks And Mortar Of Well-Being: Exploring The Housing-Health Connection, Roshanak Mehdipanah, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

Housing is a determinant of health. Increasing housing costs and worsening housing conditions have impacted populations worldwide. This Editorial aims to examine the dynamic connection between housing and health and the role of public health in addressing this relationship for a Collection launched at BMC Public Health on Housing as a determinant of health and well-being.

Quality Of Life In Male Breast Cancer: Prospective Study Of The International Male Breast Cancer Program (Eortc10085/Tbcrc029/Big2-07/Nabcg), Carolien P Schröder, Elise Van Leeuwen-Stok, Fatima Cardoso, Barbro Linderholm, Coralie Poncet, Antonio C Wolff, Vesna Bjelic-Radisic, Gustavo Werutsky, Miguel H Abreu, Ivana Bozovic-Spasojevic, Irma Den Hoed, Aafke H Honkoop, Maartje Los, Jose P Leone, Nicola S Russell, Tineke J Smilde, Annette W G Van Der Velden, Catherine Van Poznak, Marije M Vleugel, Rachel L Yung, Corneel Coens, Sharon H Giordano, Kathryn J Ruddy

Faculty, Staff and Student Publications

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.

METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.

RESULTS: Of 422 men consenting to participate, 363 …

Comparative Genomic Landscape Of Urothelial Carcinoma Of The Bladder Among Patients Of East And South Asian Genomic Ancestry, Taylor Peak, Philippe E Spiess, Roger Li, Petros Grivas, Andrea Necchi, Dean Pavlick, Richard S P Huang, Douglas Lin, Natalie Danziger, Joseph M Jacob, Gennady Bratslavsky, Jeffrey S Ross

Faculty, Staff and Student Publications

BACKGROUND: Despite the low rate of urothelial carcinoma of the bladder (UCB) in patients of South Asian (SAS) and East Asian (EAS) descent, they make up a significant portion of the cases worldwide. Nevertheless, these patients are largely under-represented in clinical trials. We queried whether UCB arising in patients with SAS and EAS ancestry would have unique genomic features compared to the global cohort.

METHODS: Formalin-fixed, paraffin-embedded tissue was obtained for 8728 patients with advanced UCB. DNA was extracted and comprehensive genomic profiling was performed. Ancestry was classified using a proprietary calculation algorithm. Genomic alterations (GAs) were determined using a …

An Update On Strategies To Deliver Protein And Peptide Drugs To The Eye, Sai H S Boddu, Devarshi Acharya, Vivek Hala, Harshil Jani, Sonal Pande, Chirag Patel, Moyad Shahwan, Renukuntla Jwala, Ketan M Ranch

Faculty, Staff and Student Publications

In the past few decades, advancements in protein engineering, biotechnology, and structural biochemistry have resulted in the discovery of various techniques that enhanced the production yield of proteins, targetability, circulating half-life, product purity, and functionality of proteins and peptides. As a result, the utilization of proteins and peptides has increased in the treatment of many conditions, including ocular diseases. Ocular delivery of large molecules poses several challenges due to their high molecular weight, hydrophilicity, unstable nature, and poor permeation through cellular and enzymatic barriers. The use of novel strategies for delivering protein and peptides such as glycoengineering, PEGylation, Fc-fusion, chitosan …

Conquer Scleroderma: Association Of Gastrointestinal Tract Symptoms In Early Disease With Resource Utilization, Sarah Luebker, Tracy M Frech, Shervin Assassi, Brian Skaug, Jessica K Gordon, Kimberly Lakin, Elana J Bernstein, Yiming Luo, Virginia D Steen, Ami A Shah, Laura K Hummers, Carrie Richardson, Duncan F Moore, Dinesh Khanna, Flavia V Castelino, Lorinda Chung, Puneet Kapoor, Faye N Hant, Victoria K Shanmugam, John M Vanburen, Jessica Alvey, Monica Harding, Ankoor Shah, Ashima Makol, Dorota Lebiedz-Odrobina, Julie K Thomas, Elizabeth R Volkmann, Jerry A Molitor, Nora Sandorfi

Faculty, Staff and Student Publications

OBJECTIVES: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients withparticipants.

METHODS: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 …

Report Of The Assay Guidance Workshop On 3-Dimensional Tissue Models For Antiviral Drug Development, Robert Jordan, Stephanie L Ford-Scheimer, Rodolfo M Alarcon, Anthony Atala, Jeffrey T Borenstein, Kyle R Brimacombe, Sara Cherry, Hans Clevers, Mindy I Davis, Simon G P Funnell, Lee Gehrke, Linda G Griffith, Abigail C Grossman, Thomas Hartung, Donald E Ingber, Nicole C Kleinstreuer, Calvin J Kuo, Emily M Lee, Christine L Mummery, Thames E Pickett, Sasirekha Ramani, Edwin A Rosado-Olivieri, Evi B Struble, Zhengpeng Wan, Mark S Williams, Matthew D Hall, Marc Ferrer, Sarine Markossian

Faculty, Staff and Students Publications

The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7-8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models' utility and limitations, use of existing 3D tissue models for antiviral …

Vertebral Tortuosity Is Associated With Increased Rate Of Cardiovascular Events In Vascular Ehlers-Danlos Syndrome, Sara B Stephens, Sherene Shalhub, Nicholas Dodd, Jesse Li, Michael Huang, Seitaro Oda, Kalyan Kancherla, Tam T Doan, Siddharth K Prakash, Justin D Weigand, Federico M Asch, Taylor Beecroft, Alana Cecchi, Teniola Shittu, Liliana Preiss, Scott A Lemaire, Richard B Devereux, Reed E Pyeritz, Kathryn W Holmes, Mary J Roman, Ronald V Lacro, Ralph V Shohet, Rajesh Krishnamurthy, Kim Eagle, Peter Byers, Dianna M Milewicz, Shaine A Morris

Faculty, Staff and Student Publications

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic

Association Of Atherosclerotic Cardiovascular Disease, Hypertension, Diabetes, And Hyperlipidemia With Gulf War Illness Among Gulf War Veterans, Sarah T Ahmed, Ruosha Li, Peter Richardson, Saurendro Ghosh, Lea Steele, Donna L White, Alice Nono Djotsa, Kellie Sims, Elizabeth Gifford, Elizabeth R Hauser, Salim S Virani, Robert Morgan, George Delclos, Drew A Helmer

Faculty, Staff and Student Publications

BACKGROUND: Approximately 30% of the 700 000 Gulf War veterans report a chronic symptom-based illness of varying severity referred to as Gulf War illness (GWI). toxic deployment-related exposures have been implicated in the cause of GWI, some of which contribute to metabolic dysregulation and lipid abnormalities. As this cohort ages, the relationship between GWI and atherosclerotic cardiovascular disease (ASCVD) is a growing concern. We evaluated associations between GWI and ASCVD, diabetes, hyperlipidemia, and hypertension in veterans of the Gulf War (1990-1991).

METHODS AND RESULTS: Analysis of survey data collected in 2014 to 2016 from a national sample of deployed Gulf …

Intracranial Stimulation And Eeg Feature Analysis Reveal Affective Salience Network Specialization, Brian A Metzger, Prathik Kalva, Madaline M Mocchi, Brian Cui, Joshua A Adkinson, Zhengjia Wang, Raissa Mathura, Kourtney Kanja, Jay Gavvala, Vaishnav Krishnan, Lu Lin, Atul Maheshwari, Ben Shofty, John F Magnotti, Jon T Willie, Sameer A Sheth, Kelly R Bijanki

Faculty, Staff and Students Publications

Emotion is represented in limbic and prefrontal brain areas, herein termed the affective salience network (ASN). Within the ASN, there are substantial unknowns about how valence and emotional intensity are processed-specifically, which nodes are associated with affective bias (a phenomenon in which participants interpret emotions in a manner consistent with their own mood). A recently developed feature detection approach ('specparam') was used to select dominant spectral features from human intracranial electrophysiological data, revealing affective specialization within specific nodes of the ASN. Spectral analysis of dominant features at the channel level suggests that dorsal anterior cingulate (dACC), anterior insula and ventral-medial …

Scribbledom: Using Scribble-Annotated Histology Images To Identify Domains In Spatial Transcriptomics Data, Mohammad Nuwaisir Rahman, Abdullah Al Noman, Abir Mohammad Turza, Mohammed Abid Abrar, Md Abul Hassan Samee, M Saifur Rahman

Faculty, Staff and Students Publications

Motivation

Spatial domain identification is a very important problem in the field of spatial transcriptomics. The state-of-the-art solutions to this problem focus on unsupervised methods, as there is lack of data for a supervised learning formulation. The results obtained from these methods highlight significant opportunities for improvement.

Results

In this article, we propose a potential avenue for enhancement through the development of a semi-supervised convolutional neural network based approach. Named “ScribbleDom”, our method leverages human expert’s input as a form of semi-supervision, thereby seamlessly combines the cognitive abilities of human experts with the computational power of machines. ScribbleDom incorporates a …

The Breast Cancer Proteome And Precision Oncology, Jonathan T Lei, Eric J Jaehnig, Hannah Smith, Matthew V Holt, Xi Li, Meenakshi Anurag, Matthew J Ellis, Gordon B Mills, Bing Zhang, Marilyne Labrie

Faculty, Staff and Students Publications

The goal of precision oncology is to translate the molecular features of cancer into predictive and prognostic tests that can be used to individualize treatment leading to improved outcomes and decreased toxicity. Success for this strategy in breast cancer is exemplified by efficacy of trastuzumab in tumors overexpressing ERBB2 and endocrine therapy for tumors that are estrogen receptor positive. However, other effective treatments, including chemotherapy, immune checkpoint inhibitors, and CDK4/6 inhibitors are not associated with strong predictive biomarkers. Proteomics promises another tier of information that, when added to genomic and transcriptomic features (proteogenomics), may create new opportunities to improve both …

Spa-Stocsy: An Automated Tool For Identifying Annotated And Non-Annotated Metabolites In High-Throughput Nmr Spectra, Xu Han, Wanli Wang, Li-Hua Ma, Ismael Ai-Ramahi, Juan Botas, Kevin Mackenzie, Genevera I Allen, Damian W Young, Zhandong Liu, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MOTIVATION: Nuclear magnetic resonance spectroscopy (NMR) is widely used to analyze metabolites in biological samples, but the analysis requires specific expertise, it is time-consuming, and can be inaccurate. Here, we present a powerful automate tool, SPatial clustering Algorithm-Statistical TOtal Correlation SpectroscopY (SPA-STOCSY), which overcomes challenges faced when analyzing NMR data and identifies metabolites in a sample with high accuracy.

RESULTS: As a data-driven method, SPA-STOCSY estimates all parameters from the input dataset. It first investigates the covariance pattern among datapoints and then calculates the optimal threshold with which to cluster datapoints belonging to the same structural unit, i.e. the metabolite. …

Making Decisions "In The Dark": Learning Through Uncertainty In Clinical Practice During Covid-19, Urvashi Vaid, Henriette Lundgren, Karen E. Watkins, Deborah Ziring, Grace A. Alcid, Victoria J. Marsick, Dimitrios Papanagnou

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

PURPOSE: The purpose of this study was to explore how decision making and informal and incidental learning (IIL) emerged in the clinical learning environment (CLE) during the height of the Covid-19 pandemic. The authors' specific interest was to better understand the IIL that took place among frontline physicians who had to navigate a CLE replete with uncertainty and complexity with the future goal of creating experiences for medical students that would simulate IIL and use uncertainty as a catalyst for learning.

METHOD: Using a modified constructivist, grounded theory approach, we describe physicians' IIL while working during times of heightened uncertainty. …

Comparison Of Bacterial Culture With Biofire® Filmarray® Multiplex Pcr Screening Of Archived Cerebrospinal Fluid Specimens From Children With Suspected Bacterial Meningitis In Nigeria, S Obaro, F Hassan-Hanga, N Medugu, Rasaq Olaosebikan, G Olanipekun, B Jibir, S Gambo, Theresa Ajose, Carissa Duru, B Ebruke, H D Davies

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnosis of bacterial meningitis remains a challenge in most developing countries due to low yield from bacterial culture, widespread use of non-prescription antibiotics, and weak microbiology laboratories. The objective of this study was to compare the yield from standard bacterial culture with the multiplex nested PCR platform, the BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire ME Panel), for cases with suspected acute bacterial meningitis.

METHODS: Following Gram stain and bacterial culture on cerebrospinal fluid (CSF) collected from children aged less than 5 years with a clinical suspicion of acute bacterial meningitis (ABM) as defined by the WHO guidelines, residual CSF specimens …

Deep Learning For Fully Automatic Tumor Segmentation On Serially Acquired Dynamic Contrast-Enhanced Mri Images Of Triple-Negative Breast Cancer, Zhan Xu, David E Rauch, Rania M Mohamed, Sanaz Pashapoor, Zijian Zhou, Bikash Panthi, Jong Bum Son, Ken-Pin Hwang, Benjamin C Musall, Beatriz E Adrada, Rosalind P Candelaria, Jessica W T Leung, Huong T C Le-Petross, Deanna L Lane, Frances Perez, Jason White, Alyson Clayborn, Brandy Reed, Huiqin Chen, Jia Sun, Peng Wei, Alastair Thompson, Anil Korkut, Lei Huo, Kelly K Hunt, Jennifer K Litton, Vicente Valero, Debu Tripathy, Wei Yang, Clinton Yam, Jingfei Ma

Faculty, Staff and Student Publications

Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients' treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for …

Intraperitoneal Paclitaxel Is A Safe And Effective Therapeutic Strategy For Treating Mucinous Appendiceal Adenocarcinoma, Ichiaki Ito, Abdelrahman M G Yousef, Saikat Chowdhury, Princess N Dickson, Zahra A Naini, Michael G White, Karianne G Fleten, Kjersti Flatmark, Keith F Fournier, Natalie W Fowlkes, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal adenocarcinomas (AAs) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal (IP) delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy …

Association Of Parental Status And Gender With Burden Of Multidisciplinary Tumor Boards Among Oncology Physicians, Brittney L Chau, Jonnby S Laguardia, Sungjin Kim, Samuel C Zhang, Eric Pletcher, Nina N Sanford, Ann C Raldow, Lisa Singer, Jun Gong, Sukhmani K Padda, Mitchell Kamrava, Tara Cohen, Devarati Mitra, Katelyn M Atkins

Faculty, Staff and Student Publications

IMPORTANCE: Tumor boards are integral to the care of patients with cancer. However, data investigating the burden of tumor boards on physicians are limited.

OBJECTIVE: To investigate what physician-related and tumor board-related factors are associated with higher tumor board burden among oncology physicians.

DESIGN, SETTING, AND PARTICIPANTS: Tumor board burden was assessed by a cross-sectional convenience survey posted on social media and by email to Cedars-Sinai Medical Center cancer physicians between March 3 and April 3, 2022. Tumor board start times were independently collected by email from 22 top cancer centers.

MAIN OUTCOMES AND MEASURES: Tumor board burden was measured …