Medical Specialties Commons^™

Progressive Muscle Relaxation Exercises In Patients With Covid-19: Systematic Review And Meta-Analysis, Abubeker Alebachew Seid, Ahmed Adem Mohammed, Aragaw Asfaw Hasen

Faculty, Staff and Student Publications

BACKGROUND: Patients with COVID-19 will experience high levels of anxiety and depression and poor levels of sleep and quality of life (QoL) due to isolation treatment and uncertain outcomes. Progressive muscle relaxation (PMR) exercises show promising treatment effects on mental health and sleep problems and overall QoL in COVID-19 patients. This study aimed to evaluate the efficacy and safety of PMR exercises in patients with COVID-19.

METHODS: Both experimental and non-experimental studies related to PMR and COVID-19 were systematically searched in the PubMed, Cochrane Library, PEDro and HINARI databases for studies published from the occurrence of the pandemic to December …

Distribution Of Serum Uric Acid Concentration And Its Association With Lipid Profiles: A Single-Center Retrospective Study In Children Aged 3 To 12 Years With Adenoid And Tonsillar Hypertrophy, Jiating Yu, Xin Liu, Honglei Ji, Yawei Zhang, Hanqiang Zhan, Ziyin Zhang, Jianguo Wen, Zhimin Wang

Faculty, Staff and Student Publications

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy.

METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were …

Prmt3-Mediated Arginine Methylation Of Igf2bp1 Promotes Oxaliplatin Resistance In Liver Cancer, Yunxing Shi, Yi Niu, Yichuan Yuan, Kai Li, Chengrui Zhong, Zhiyu Qiu, Keren Li, Zhu Lin, Zhiwen Yang, Dinglan Zuo, Jiliang Qiu, Wei He, Chenwei Wang, Yadi Liao, Guocan Wang, Yunfei Yuan, Binkui Li

Faculty, Staff and Student Publications

Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clinic. Through functional screening using CRISPR/Cas9 activation library, transcriptomic profiling of clinical samples, and functional validation in vitro and in vivo, we identify PRMT3 as a key driver of oxaliplatin resistance. Mechanistically, PRMT3-mediated oxaliplatin-resistance is in part dependent on the methylation of IGF2BP1 at R452, which is critical for the function of IGF2BP1 in stabilizing the mRNA of HEG1, an effector of PRMT3-IGF2BP1 axis. Also, PRMT3 overexpression may serve as a biomarker for oxaliplatin resistance …

Technology Implementation For Mental Health End Users: A Model To Guide Digital Transformation For Inpatient Mental Health Professionals, Jessa Lin Westheimer, Nidal Moukaddam, Jan A Lindsay, Ashutosh Sabharwal, Bijan Najafi, Peter A Iacobelli, Robert J Boland, Michelle A Patriquin

Faculty, Staff and Students Publications

Digital transformation is the adoption of digital technologies by an entity in an effort to increase operational efficiency. In mental health care, digital transformation entails technology implementation to improve the quality of care and mental health outcomes. Most psychiatric hospitals rely heavily on "high-touch" interventions or those that require in-person, face-to-face interaction with the patient. Those that are exploring digital mental health care interventions, particularly for outpatient care, often copiously commit to the "high-tech" model, losing the crucial human element. The process of digital transformation, especially within acute psychiatric treatment settings, is in its infancy. Existing implementation models outline the …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Mutation-Agnostic Detection Of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures, Mohamed A Gouda, Dzifa Y Duose, Morten Lapin, Stephanie Zalles, Helen J Huang, Yuanxin Xi, Xiaofeng Zheng, Amira I Aldesoky, Alshimaa M Alhanafy, Mohamed A Shehata, Jing Wang, Scott Kopetz, Funda Meric-Bernstam, Ignacio I Wistuba, Rajyalakshmi Luthra, Filip Janku

Faculty, Staff and Student Publications

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal …

An Expedited Strategy For Accurate And Timely Integrated Molecular Diagnosis Of Gliomas, Timothy A Gregory, Garret L Williford, Jacob M Maronge, Kristin Alfaro, Gregory N Fuller, John De Groot, Vinay K Puduvalli, Leomar Y Ballester, Nazanin K Majd

Faculty, Staff and Student Publications

No abstract provided.

Brain Metastases From Biliary Tract Cancer: Case Series And Clinicogenomic Analysis, Grace N Dodoo, Brian De, Sunyoung S Lee, Joseph Abi Jaoude, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Kalman A Katlowitz, Jacob J Mandel, Thomas H Beckham, Bruce D Minsky, Grace L Smith, Emma B Holliday, Albert C Koong, Prajnan Das, Cullen M Taniguchi, Milind Javle, Eugene J Koay, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.

MATERIALS AND METHODS: A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.

RESULTS: Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis …

Bi-Allelic Variants In The Esam Tight-Junction Gene Cause A Neurodevelopmental Disorder Associated With Fetal Intracranial Hemorrhage, Mauro Lecca, Davut Pehlivan, Damià Heine Suñer, Karin Weiss, Thibault Coste, Markus Zweier, Yavuz Oktay, Nada Danial-Farran, Vittorio Rosti, Maria Paola Bonasoni, Alessandro Malara, Gianluca Contrò, Roberta Zuntini, Marzia Pollazzon, Rosario Pascarella, Alberto Neri, Carlo Fusco, Dana Marafi, Tadahiro Mitani, Jennifer Ellen Posey, Sadik Etka Bayramoglu, Alper Gezdirici, Jessica Hernandez-Rodriguez, Emilia Amengual Cladera, Elena Miravet, Jorge Roldan-Busto, María Angeles Ruiz, Cristofol Vives Bauzá, Liat Ben-Sira, Sabine Sigaudy, Anaïs Begemann, Sheila Unger, Serdal Güngör, Semra Hiz, Ece Sonmezler, Yoav Zehavi, Michael Jerdev, Alessandra Balduini, Orsetta Zuffardi, Rita Horvath, Hanns Lochmüller, Anita Rauch, Livia Garavelli, Elisabeth Tournier-Lasserve, Ronen Spiegel, James R Lupski, Edoardo Errichiello

Faculty, Staff and Students Publications

The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs∗33) variant, identified in six individuals from four independent families of Southeastern Anatolia, severely impaired the in vitro tubulogenic process of endothelial colony-forming cells, recapitulating previous evidence in null mice, and caused lack of ESAM expression in …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Chemical Reprogramming Takes The Fast Lane, Emily J Park, Srikanth Kodali, Bruno Di Stefano

Faculty, Staff and Students Publications

Small molecule-induced cell fate transitions are characterized by low efficiency and slow kinetics. An optimized chemical reprogramming approach now facilitates the robust and rapid conversion of somatic cells to pluripotent stem cells, unlocking exciting avenues to study and manipulate human cell identity.

Evaluation Of Focal Adhesion Mediated Subcellular Curvature Sensing In Response To Engineered Extracellular Matrix, Daniel T Bowers, Mary Elizabeth Mcculloch, Justin L Brown

Faculty, Staff and Student Publications

Fibril curvature is bioinstructive to attached cells. Similar to natural healthy tissues, an engineered extracellular matrix can be designed to stimulate cells to adopt desired phenotypes. To take full advantage of the curvature control in biomaterial fabrication methodologies, an understanding of the response to fibril subcellular curvature is required. In this work, we examined morphology, signaling, and function of human cells attached to electrospun nanofibers. We controlled curvature across an order of magnitude using nondegradable poly(methyl methacrylate) (PMMA) attached to a stiff substrate with flat PMMA as a control. Focal adhesion length and the distance of maximum intensity from the …

Comprehensive Proteomics And Platform Validation Of Urinary Biomarkers For Bladder Cancer Diagnosis And Staging, Kamala Vanarsa, Jessica Castillo, Long Wang, Kyung Hyun Lee, Claudia Pedroza, Yair Lotan, Chandra Mohan

Faculty, Staff and Student Publications

BACKGROUND: Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease.

METHODS: An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity.

RESULTS: Systems biology analysis implicated molecular functions related to the …

Temporal Machine Learning Analysis Of Prior Mammograms For Breast Cancer Risk Prediction, Hui Li, Kayla Robinson, Li Lan, Natalie Baughan, Chun-Wai Chan, Matthew Embury, Gary J Whitman, Randa El-Zein, Isabelle Bedrosian, Maryellen L Giger

Faculty, Staff and Student Publications

The identification of women at risk for sporadic breast cancer remains a clinical challenge. We hypothesize that the temporal analysis of annual screening mammograms, using a long short-term memory (LSTM) network, could accurately identify women at risk of future breast cancer. Women with an imaging abnormality, which had been biopsy-confirmed to be cancer or benign, who also had antecedent imaging available were included in this case-control study. Sequences of antecedent mammograms were retrospectively collected under HIPAA-approved guidelines. Radiomic and deep-learning-based features were extracted on regions of interest placed posterior to the nipple in antecedent images. These features were input to …

The Type 2 Diabetes Knowledge Portal: An Open Access Genetic Resource Dedicated To Type 2 Diabetes And Related Traits, Maria C Costanzo, Marcin Von Grotthuss, Jeffrey Massung, Dongkeun Jang, Lizz Caulkins, Ryan Koesterer, Clint Gilbert, Ryan P Welch, Parul Kudtarkar, Quy Hoang, Andrew P Boughton, Preeti Singh, Ying Sun, Marc Duby, Annie Moriondo, Trang Nguyen, Patrick Smadbeck, Benjamin R Alexander, Mackenzie Brandes, Mary Carmichael, Peter Dornbos, Todd Green, Kenneth C Huellas-Bruskiewicz, Yue Ji, Alexandria Kluge, Aoife C Mcmahon, Josep M Mercader, Oliver Ruebenacker, Sebanti Sengupta, Dylan Spalding, Daniel Taliun, Philip Smith, Melissa K Thomas, Beena Akolkar, M Julia Brosnan, Andriy Cherkas, Audrey Y Chu, Eric B Fauman, Caroline S Fox, Tania Nayak Kamphaus, Melissa R Miller, Lynette Nguyen, Afshin Parsa, Dermot F Reilly, Hartmut Ruetten, David Wholley, Norann A Zaghloul, Gonçalo R Abecasis, David Altshuler, Thomas M Keane, Mark I Mccarthy, Kyle J Gaulton, Jose C Florez, Michael Boehnke, Noël P Burtt, Jason Flannick

Faculty, Staff and Student Publications

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin …

Identification Of Protein Biomarkers Of The Dietary Approaches To Stop Hypertension Diet In Randomized Feeding Studies And Validation In An Observational Study, Hyunju Kim, Alice H Lichtenstein, Peter Ganz, Shutong Du, Olive Tang, Bing Yu, Nilanjan Chatterjee, Lawrence J Appel, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background

The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study.

Methods and Results

Large‐scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8‐week and 4‐week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH‐Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins …

Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Student Publications

Our current understanding of brain rhythms is based on quantifying their instantaneous or time-averaged characteristics. What remains unexplored is the actual structure of the waves-their shapes and patterns over finite timescales. Here, we study brain wave patterning in different physiological contexts using two independent approaches: The first is based on quantifying stochasticity relative to the underlying mean behavior, and the second assesses "orderliness" of the waves' features. The corresponding measures capture the waves' characteristics and abnormal behaviors, such as atypical periodicity or excessive clustering, and demonstrate coupling between the patterns' dynamics and the animal's location, speed, and acceleration. Specifically, we …

Swi/Snf Blockade Disrupts Pu1-Directed Enhancer Programs In Normal Hematopoietic Cells And Acute Myeloid Leukemia, Courtney Chambers, Katerina Cermakova, Yuen San Chan, Kristen Kurtz, Katharina Wohlan, Andrew Henry Lewis, Christiana Wang, Anh Pham, Milan Dejmek, Michal Sala, Mario Loeza Cabrera, Rogelio Aguilar, Radim Nencka, H Daniel Lacorazza, Rachel E Rau, H Courtney Hodges

Faculty, Staff and Students Publications

UNLABELLED: In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition …

Large-Scale Analysis Of Structural Brain Asymmetries In Schizophrenia Via The Enigma Consortium, Dick Schijven, Merel C Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M C De Zwarte, Neeltje E M Van Haren, Wiepke Cahn, Hilleke E Hulshoff Pol, René S Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García De La Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T Westlye, Ingrid Agartz, Ole A Andreassen, Erik G Jönsson, Peter Kochunov, Jason M Bruggemann, Stanley V Catts, Patricia T Michie, Bryan J Mowry, Yann Quidé, Paul E Rasser, Ulrich Schall, Rodney J Scott, Vaughan J Carr, Melissa J Green, Frans A Henskens, Carmel M Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W Weickert, Lieuwe De Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G Ringwald, Frederike Stein, Andreas Jansen, Tilo T J Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D Satterthwaite, Juan Bustillo, Daniel H Mathalon, Adrian Preda, Vince D Calhoun, Judith M Ford, Steven G Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese Van Amelsvoort, Erin W Dickie, Aristotle N Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M Mcintosh, Heather C Whalley, Stephen M Lawrie, Stefan Du Plessis, Hilmar K Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T Edmond, Kelly Rootes-Murdy, Julia M Stephen, Andrew R Mayer, Linda A Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M Díaz-Caneja, Joost Janssen, Noemi G Lois, Celso Arango, Alexander S Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M Howells, Dan J Stein, Henk S Temmingh, Ana M Diaz-Zuluaga, Julian A Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E Fisher, Barbara Franke, David C Glahn, Ruben C Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E Medland, Paul M Thompson, Jessica A Turner, Theo G M Van Erp, Clyde Francks

Faculty, Staff and Students Publications

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small …

Pattern Dynamics And Stochasticity Of The Brain Rhythms, Clarissa Hoffman, Jingheng Cheng, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Our current understanding of brain rhythms is based on quantifying their instantaneous or time-averaged characteristics. What remains unexplored is the actual structure of the waves—their shapes and patterns over finite timescales. Here, we study brain wave patterning in different physiological contexts using two independent approaches: The first is based on quantifying stochasticity relative to the underlying mean behavior, and the second assesses “orderliness” of the waves’ features. The corresponding measures capture the waves’ characteristics and abnormal behaviors, such as atypical periodicity or excessive clustering, and demonstrate coupling between the patterns’ dynamics and the animal’s location, speed, and acceleration. Specifically, we …

Early Lead Extraction For Infected Implanted Cardiac Electronic Devices: Jacc Review Topic Of The Week, Dhanunjaya R Lakkireddy, Douglas S Segar, Ami Sood, Maryann Wu, Archana Rao, M Rizwan Sohail, Sean D Pokorney, Carina Blomström-Lundqvist, Jonathan P Piccini, Christopher B Granger

Faculty, Staff and Students Publications

Infection remains a serious complication associated with the cardiac implantable electronic devices (CIEDs), leading to substantial clinical and economic burden globally. This review assesses the burden of cardiac implantable electronic device infection (CIED-I), evidence for treatment recommendations, barriers to early diagnosis and appropriate therapy, and potential solutions. Multiple clinical practice guidelines recommended complete system and lead removal for CIED-I when appropriate. CIED extraction for infection has been consistently reported with high success, low complication, and very low mortality rates. Complete and early extraction was associated with significantly better clinical and economic outcome compared with no or late extraction. However, significant …

Cd73-Dependent Adenosine Signaling Through Adora2b Drives Immunosuppression In Ductal Pancreatic Cancer, Erika Y Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J O'Brien, Lincoln N Strickland, Le Li, Emily Vucic, Amanda N Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C Thosani, John S Bynon, Curtis J Wray, Dafna Bar-Sagi, Kyle L Poulsen, Lana A Vornik, Michelle I Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H Brown, Tingting Mills, Holger K Eltzschig, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. …

The Effects Of Racism And Resilience On Black Stroke- Survivor Quality Of Life: Study Protocol And Rationale For A Mixed-Methods Approach, Xiude Fan, Junming Han, Enfa Zhao, Jiansong Fang, Dawei Wang, Yiping Cheng, Yingzhou Shi, Zhen Wang, Zhenyu Yao, Peng Lu, Tianbao Liu, Qihang Li, Kyle L Poulsen, Zhongshang Yuan, Yongfeng Song, Jiajun Zhao

Faculty, Staff and Student Publications

Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% …

Successful Heart-Liver Transplant Using Dual-Organ Normothermic Perfusion In A Patient With Fontan Failure, Anton Kozyryev, Daniel Lemen, Jessica Dunn, Steven E Rokita

Faculty, Staff and Student Publications

Iodotyrosine deiodinase (IYD) is unusual in its reliance on flavin to promote reductive dehalogenation of halotyrosines under aerobic conditions. Applications of this activity can be envisioned for bioremediation, but expansion of its specificity requires an understanding of the mechanistic steps that limit the rate of turnover. Key processes capable of controlling steady-state turnover have now been evaluated and described in this study. While proton transfer is necessary for converting the electron-rich substrate into an electrophilic intermediate suitable for reduction, kinetic solvent deuterium isotope effects suggest that this process does not contribute to the overall efficiency of catalysis under neutral conditions. …

Il6 Mediates Suppression Of T- And Nk-Cell Function In Emt-Associated Tki-Resistant Egfr-Mutant Nsclc, Sonia A Patel, Monique B Nilsson, Yan Yang, Xiuning Le, Hai T Tran, Yasir Y Elamin, Xiaoxing Yu, Fahao Zhang, Alissa Poteete, Xiaoyang Ren, Li Shen, Jing Wang, Seyed Javad Moghaddam, Tina Cascone, Michael Curran, Don L Gibbons, John V Heymach

Faculty, Staff and Student Publications

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype.

Experimental design: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and …

Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette

Faculty, Staff and Student Publications

Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote …

Privacy Preservation In Smart Meters: Current Status, Challenges And Future Directions, Jonathan Kua, Mohammad Belayet Hossain, Iynkaran Natgunanathan, Yong Xiang

Faculty, Staff and Student Publications

Recent years have seen the rapid development of technologies in Smart Grids (SGs) to enhance electricity networks with digital and data communication technologies. SGs can proactively detect, react, and respond to dynamic changes in the network. SGs can also enhance the efficiency and reliability of electricity supplies and promote the integration of renewable energy sources. Smart Meters (SMs) are often seen as the first step to a successful implementation of SGs. While SMs enable Utility Providers and consumers to obtain near real-time information of energy consumption, they can also be exploited to infer sensitive consumer data. Therefore, privacy preservation in …

Induction Of Innate Inflammatory Pathways In The Corneal Epithelium In The Desiccating Stress Dry Eye Model, Zhiyuan Yu, Ghasem Yazdanpanah, Jehan Alam, Cintia S De Paiva, Stephen Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To determine whether 24-hour exposure to the desiccating stress (DS) dry eye model induces NF-kB and NLRP3 inflammasome pathways in the mouse cornea epithelium.

METHODS: Six- to 8-week-old C57BL/6J mice were housed under normal humidity (nonstressed) or subjected to DS from a drafty, low-humidity environment combined with subcutaneous scopolamine four times/day for one day to suppress tear production (DS1). Cornea whole mounts were prepared for immunofluorescent staining, or the corneal epithelium was scraped for NF-kB p-p65 ELISA, Western blot, or real-time PCR to detect NF-kB and inflammasome pathway proteins and gene transcripts, respectively.

RESULTS: NF-kB phospho-p65 protein, nuclear NF-kB …

Longitudinal Global Transcriptomic Profiling Of Preclinical Systemic Sclerosis Reveals Molecular Changes Associated With Disease Progression, Chiara Bellocchi, Lorenzo Beretta, Xuan Wang, Marka A Lyons, Maurizio Marchini, Maurizio Lorini, Vincenzo Carbonelli, Nicola Montano, Shervin Assassi

Faculty, Staff and Student Publications

Objective: To investigate peripheral blood cell (PBCs) global gene expression profile of SSc at its preclinical stage (PreSSc) and to characterize the molecular changes associated with progression to a definite disease over time.

Material and methods: Clinical data and PBCs of 33 participants with PreSSc and 16 healthy controls (HCs) were collected at baseline and follow-up (mean 4.2 years). Global gene expression profiling was conducted by RNA sequencing and a modular analysis was performed.

Results: Comparison of baseline PreSSc to HCs revealed 2889 differentially expressed genes. Interferon signalling was the only activated pathway among top over-represented pathways. Moreover, 10 modules …

Increases In Group A Streptococcal Infections In The Pediatric Population In Houston, Tx, 2022, Aya Aboulhosn, Misu A Sanson, Luis Alberto Vega, Maria G Segura, Lauren M Summer, Marritta Joseph, J Chase Mcneil, Anthony R Flores

Faculty, Staff and Student Publications

Beginning in October 2022, we observed a substantial increase in the total number of cases of invasive GAS disease (iGAS) in the pediatric population in Houston, TX. Emm12 GAS strains were disproportionately represented but the overall proportion of iGAS infections observed during the current spike was similar to pre-pandemic years.