Medical Specialties Commons^™

Integrative Genomic Analyses Reveal Putative Cell Type-Specific Targets Of The Drosophila Ets Transcription Factor Pointed, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yoon-Kyung Shim, Graeme Mardon

Faculty, Staff and Students Publications

The Ets domain transcription factors direct diverse biological processes throughout all metazoans and are implicated in development as well as in tumor initiation, progression and metastasis. The Drosophila Ets transcription factor Pointed (Pnt) is the downstream effector of the Epidermal growth factor receptor (Egfr) pathway and is required for cell cycle progression, specification, and differentiation of most cell types in the larval eye disc. Despite its critical role in development, very few targets of Pnt have been reported previously. Here, we employed an integrated approach by combining genome-wide single cell and bulk data to identify putative cell type-specific Pnt targets. …

Virology-The Path Forward, Angela L Rasmussen, Gigi K Gronvall, Anice C Lowen, Felicia Goodrum, James Alwine, Kristian G Andersen, Simon J Anthony, Joel Baines, Arinjay Banerjee, Andrew J Broadbent, Christopher B Brooke, Samuel K Campos, Patrizia Caposio, Arturo Casadevall, Gary C Chan, Anna R Cliffe, Donna Collins-Mcmillen, Nancy Connell, Blossom Damania, Matthew D Daugherty, Kari Debbink, Terence S Dermody, Daniel Dimaio, W Paul Duprex, Michael Emerman, Denise A Galloway, Robert F Garry, Stephen A Goldstein, Alexander L Greninger, Amy L Hartman, Brenda G Hogue, Stacy M Horner, Peter J Hotez, Jae U Jung, Jeremy P Kamil, Stephanie M Karst, Lou Laimins, Seema S Lakdawala, Igor Landais, Michael Letko, Brett Lindenbach, Shan-Lu Liu, Micah Luftig, Grant Mcfadden, Andrew Mehle, Juliet Morrison, Anne Moscona, Elke Mühlberger, Joshua Munger, Karl Münger, Eain Murphy, Christopher J Neufeldt, Janko Z Nikolich, Christine M O'Connor, Andrew Pekosz, Sallie R Permar, Julie K Pfeiffer, Saskia V Popescu, John G Purdy, Vincent R Racaniello, Charles M Rice, Jonathan A Runstadler, Martin J Sapp, Rona S Scott, Gregory A Smith, Erin M Sorrell, Emily Speranza, Daniel Streblow, Scott A Tibbetts, Zsolt Toth, Koenraad Van Doorslaer, Susan R Weiss, Elizabeth A White, Timothy M White, Christiane E Wobus, Michael Worobey, Satoko Yamaoka, Andrew Yurochko

Faculty, Staff and Students Publications

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is …

Extreme Drought Impacts Have Been Underestimated In Grasslands And Shrublands Globally, Melinda D Smith, Kate D Wilkins, Martin C Holdrege, Peter Wilfahrt, Scott L Collins, Alan K Knapp, Osvaldo E Sala, Jeffrey S Dukes, Richard P Phillips, Laura Yahdjian, Laureano A Gherardi, Timothy Ohlert, Claus Beier, Lauchlan H Fraser, Anke Jentsch, Michael E Loik, Fernando T Maestre, Sally A Power, Qiang Yu, Andrew J Felton, Seth M Munson, Yiqi Luo, Hamed Abdoli, Mehdi Abedi, Concepción L Alados, Juan Alberti, Moshe Alon, Hui An, Brian Anacker, Maggie Anderson, Harald Auge, Seton Bachle, Khadijeh Bahalkeh, Michael Bahn, Amgaa Batbaatar, Taryn Bauerle, Karen H Beard, Kai Behn, Ilka Beil, Lucio Biancari, Irmgard Blindow, Viviana Florencia Bondaruk, Elizabeth T Borer, Edward W Bork, Carlos Martin Bruschetti, Kerry M Byrne, James F Cahill, Dianela A Calvo, Michele Carbognani, Augusto Cardoni, Cameron N Carlyle, Miguel Castillo-Garcia, Scott X Chang, Jeff Chieppa, Marcus V Cianciaruso, Ofer Cohen, Amanda L Cordeiro, Daniela F Cusack, Sven Dahlke, Pedro Daleo, Carla M D'Antonio, Lee H Dietterich, Tim S Doherty, Maren Dubbert, Anne Ebeling, Nico Eisenhauer, Felícia M Fischer, T'Ai G W Forte, Tobias Gebauer, Beatriz Gozalo, Aaron C Greenville, Karlo G Guidoni-Martins, Heather J Hannusch, Siri Vatsø Haugum, Yann Hautier, Mariet Hefting, Hugh A L Henry, Daniela Hoss, Johannes Ingrisch, Oscar Iribarne, Forest Isbell, Yari Johnson, Samuel Jordan, Eugene F Kelly, Kaitlin Kimmel, Juergen Kreyling, György Kröel-Dulay, Alicia Kröpfl, Angelika Kübert, Andrew Kulmatiski, Eric G Lamb, Klaus Steenberg Larsen, Julie Larson, Jason Lawson, Cintia V Leder, Anja Linstädter, Jielin Liu, Shirong Liu, Alexandra G Lodge, Grisel Longo, Alejandro Loydi, Junwei Luan, Frederick Curtis Lubbe, Craig Macfarlane, Kathleen Mackie-Haas, Andrey V Malyshev, Adrián Maturano-Ruiz, Thomas Merchant, Daniel B Metcalfe, Akira S Mori, Edwin Mudongo, Gregory S Newman, Uffe N Nielsen, Dale Nimmo, Yujie Niu, Paola Nobre, Rory C O'Connor, Romà Ogaya, Gastón R Oñatibia, Ildikó Orbán, Brooke Osborne, Rafael Otfinowski, Meelis Pärtel, Josep Penuelas, Pablo L Peri, Guadalupe Peter, Alessandro Petraglia, Catherine Picon-Cochard, Valério D Pillar, Juan Manuel Piñeiro-Guerra, Laura W Ploughe, Robert M Plowes, Cristy Portales-Reyes, Suzanne M Prober, Yolanda Pueyo, Sasha C Reed, Euan G Ritchie, Dana Aylén Rodríguez, William E Rogers, Christiane Roscher, Ana M Sánchez, Bráulio A Santos, María Cecilia Scarfó, Eric W Seabloom, Baoku Shi, Lara Souza, Andreas Stampfli, Rachel J Standish, Marcelo Sternberg, Wei Sun, Marie Sünnemann, Michelle Tedder, Pål Thorvaldsen, Dashuan Tian, Katja Tielbörger, Alejandro Valdecantos, Liesbeth Van Den Brink, Vigdis Vandvik, Mathew R Vankoughnett, Liv Guri Velle, Changhui Wang, Yi Wang, Glenda M Wardle, Christiane Werner, Cunzheng Wei, Georg Wiehl, Jennifer L Williams, Amelia A Wolf, Michaela Zeiter, Fawei Zhang, Juntao Zhu, Ning Zong, Xiaoan Zuo

Faculty, Staff and Students Publications

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on …

Assessing Influence Of Immigrant Status And Other Social Determinants Of Health On Community Psychiatry, Agnes M. Cruz, Jorge A. Romero Ortiz, Diana Chapa

Research Symposium

Background/purpose: Social determinants of health are fundamental and structural factors that affect people’s lives and impact their health and longevity. Differences in social determinants of health across populations and communities account for major health disparities between them. The purpose of this paper is to assess how social determinants of health have impacted the health outcomes in patients from our community psychiatry clinics, to evaluate the impact of irregular immigration status as an independent social determinant of health, and to investigate the use of SDOH screening instrument in our clinics.

Methods: An online questionnaire was sent to community psychiatry providers in …

Characterization Of Variant Rnas Encapsidated During Bromovirus Infection By High-Throughput Sequencing, Sarah Dexheimer, Nipin Shrestha, Bandana Sharma Chapagain, Jozef J. Bujarski, Yanbin Yin

Food for Health: Publications

Previously, we described the RNA recombinants accumulating in tissues infected with the bromoviruses BMV (Brome mosaic virus) and CCMV (Cowpea chlorotic mottle virus). In this work, we characterize the recombinants encapsidated inside the purified virion particles of BMV and CCMV. By using a tool called the Viral Recombination Mapper (ViReMa) that detects recombination junctions, we analyzed a high number of high-throughput sequencing (HTS) short RNA sequence reads. Over 28% of BMV or CCMV RNA reads did not perfectly map to the viral genomes. ViReMa identified 1.40% and 1.83% of these unmapped reads as the RNA recombinants, respectively, in BMV and …

Post-Capillary Pulmonary Hypertension: Clinical Review, Joshua Riley, James Fradin, Douglas Russ, Eric Warner, Yevgeniy Brailovsky, Indranee Rajapreyar

Department of Medicine Faculty Papers

Pulmonary hypertension (PH) caused by left heart disease, also known as post-capillary PH, is the most common etiology of PH. Left heart disease due to systolic dysfunction or heart failure with preserved ejection fraction, valvular heart disease, and left atrial myopathy due to atrial fibrillation are causes of post-capillary PH. Elevated left-sided filling pressures cause pulmonary venous congestion due to backward transmission of pressures and post-capillary PH. In advanced left-sided heart disease or valvular heart disease, chronic uncontrolled venous congestion may lead to remodeling of the pulmonary arterial system, causing combined pre-capillary and post-capillary PH. The hemodynamic definition of post-capillary …

A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …

Unexpected Inhibition Of The Lipid Kinase Pikfyve Reveals An Epistatic Role For P38 Mapks In Endolysosomal Fission And Volume Control, Daric J Wible, Zalak Parikh, Eun Jeong Cho, Miao-Der Chen, Collene R Jeter, Somshuvra Mukhopadhyay, Kevin N Dalby, Shankar Varadarajan, Shawn B Bratton

Faculty, Staff and Student Publications

p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. Subsequent studies, however, have suggested that the associated cytoplasmic vacuolation resulted from off-target inhibition of an unidentified enzyme. Herein, we report that SB203580-induced vacuolation is rapid, reversible, and relies on the class III phosphatidylinositol 3-kinase (PIK3C3) complex and the production of phosphatidylinositol 3-phosphate [PI(3)P] but not on autophagy per se. Rather, vacuolation resulted from the accumulation of Rab7 on late endosome and lysosome (LEL) membranes, combined with …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Sigma Leverages Protein Structural Information To Predict The Pathogenicity Of Missense Variants, Hengqiang Zhao, Huakang Du, Sen Zhao, Zefu Chen, Yaqi Li, Kexin Xu, Bowen Liu, Xi Cheng, Wen Wen, Guozhuang Li, Guilin Chen, Zhengye Zhao, Guixing Qiu, Deciphering Disorders Involving Scoliosis & Comorbidities (Disco) Study, Pengfei Liu, Terry Jianguo Zhang, Zhihong Wu, Nan Wu

Faculty, Staff and Students Publications

Leveraging protein structural information to evaluate pathogenicity has been hindered by the scarcity of experimentally determined 3D protein. With the aid of AlphaFold2 predictions, we developed the structure-informed genetic missense mutation assessor (SIGMA) to predict missense variant pathogenicity. In comparison with existing predictors across labeled variant datasets and experimental datasets, SIGMA demonstrates superior performance in predicting missense variant pathogenicity (AUC = 0.933). We found that the relative solvent accessibility of the mutated residue contributed greatly to the predictive ability of SIGMA. We further explored combining SIGMA with other top-tier predictors to create SIGMA+, proving highly effective for variant pathogenicity prediction …

Extracellular Carriers Control Lipid-Dependent Secretion, Delivery, And Activity Of Wnt Morphogens, Taciani De Almeida Magalhaes, Jingjing Liu, Charlene Chan, Kleiton Silva Borges, Jiuchun Zhang, Andrew J Kane, Bradley M Wierbowski, Yunhui Ge, Zhiwen Liu, Prabhath Mannam, Daniel Zeve, Ron Weiss, David T Breault, Pengxiang Huang, Adrian Salic

Faculty, Staff and Students Publications

WNT morphogens trigger signaling pathways fundamental for embryogenesis, regeneration, and cancer. WNTs are modified with palmitoleate, which is critical for binding Frizzled (FZD) receptors and activating signaling. However, it is unknown how WNTs are released and spread from cells, given their strong lipid-dependent membrane attachment. We demonstrate that secreted FZD-related proteins and WNT inhibitory factor 1 are WNT carriers, potently releasing lipidated WNTs and forming active soluble complexes. WNT release occurs by direct handoff from the membrane protein WNTLESS to the carriers. In turn, carriers donate WNTs to glypicans and FZDs involved in WNT reception and to the NOTUM hydrolase, …

Crispr-Dipoff: An Interpretable Deep Learning Approach For Crispr Cas-9 Off-Target Prediction, Md Toufikuzzaman, Md Abul Hassan Samee, M Sohel Rahman

Faculty, Staff and Students Publications

CRISPR Cas-9 is a groundbreaking genome-editing tool that harnesses bacterial defense systems to alter DNA sequences accurately. This innovative technology holds vast promise in multiple domains like biotechnology, agriculture and medicine. However, such power does not come without its own peril, and one such issue is the potential for unintended modifications (Off-Target), which highlights the need for accurate prediction and mitigation strategies. Though previous studies have demonstrated improvement in Off-Target prediction capability with the application of deep learning, they often struggle with the precision-recall trade-off, limiting their effectiveness and do not provide proper interpretation of the complex decision-making process of …

Microglia-Derived Exosomes Modulate Myelin Regeneration Via Mir-615-5p/Myrf Axis, Xiao-Yu Ji, Yu-Xin Guo, Li-Bin Wang, Wen-Cheng Wu, Jia-Qi Wang, Jin He, Rui Gao, Javad Rasouli, Meng-Yuan Gao, Zhen-Hai Wang, Dan Xiao, Wei-Feng Zhang, Bogoljub Ciric, Yuan Zhang, Xing Li

Department of Neurology Faculty Papers

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to …

The Impact Of Chronic Comorbidities On Outcomes In Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Saqib H. Baig, Erika J. Yoo

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

INTRODUCTION: Idiopathic pulmonary fibrosis is a chronic progressive lung disease of unknown cause with a high associated mortality. We aimed to compare the impact of chronic medical conditions on hospital outcomes of patients with acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF).

METHODS: This was a retrospective cohort study using the NIS database from 2016 to 2018. We included patients aged 60 and older hospitalized in academic medical centers with the diagnoses of IPF and acute respiratory failure. We examined factors associated with hospital mortality and length of stay (LOS) using survey-weighted multivariate logistic and negative binomial regression.

RESULTS: Out of …

Occupational Therapy’S Opportunity To Impact Care At The End Of Life, Macey Genzlinger, Mackenzie L. Feldhacker

Student Journal of Occupational Therapy

Navigating and managing the end of life can be difficult. The focus of occupational therapy in care at the end of life is to aid the patient and caregiver through these challenges by facilitating improved safety, comfort, and quality of life through the participation in meaningful occupations. Despite the ways that occupational therapy benefits these patients, occupational therapy involvement in care at the end of life is misunderstood, under-researched, and underutilized. There is a general lack of awareness regarding this topic and a stigma that occupational therapy focuses only on rehabilitation and therefore does not belong in care at the …

Durvalumab Plus Carboplatin/Paclitaxel Followed By Maintenance Durvalumab With Or Without Olaparib As First-Line Treatment For Advanced Endometrial Cancer: The Phase Iii Duo-E Trial, Shannon N Westin, Kathleen Moore, Hye Sook Chon, Jung-Yun Lee, Jessica Thomes Pepin, Michael Sundborg, Ayelet Shai, Joseph De La Garza, Shin Nishio, Michael A Gold, Ke Wang, Kristi Mcintyre, Todd D Tillmanns, Stephanie V Blank, Ji-Hong Liu, Michael Mccollum, Fernando Contreras Mejia, Tadaaki Nishikawa, Kathryn Pennington, Zoltan Novak, Andreia Cristina De Melo, Jalid Sehouli, Dagmara Klasa-Mazurkiewicz, Christos Papadimitriou, Marta Gil-Martin, Birute Brasiuniene, Conor Donnelly, Paula Michelle Del Rosario, Xiaochun Liu, Els Van Nieuwenhuysen, Duo-E Investigators

Faculty, Staff and Student Publications

PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.

METHODS: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival …

Mypathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment Of A Tissue-Agnostic Cohort Of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors, Christopher J Sweeney, John D Hainsworth, Ron Bose, Howard A Burris, Razelle Kurzrock, Charles Swanton, Claire F Friedman, David R Spigel, Tania Szado, Katja Schulze, Richard Price, Julia Malato, Amy A Lo, Jonathan Levy, Yong Wang, Wei Yu, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The MyPathway multiple-basket study (ClinicalTrials.gov identifier: NCT02091141) is evaluating targeted therapies in nonindicated tumors with relevant molecular alterations. We assessed pertuzumab + trastuzumab in a tissue-agnostic cohort of adult patients with human epidermal growth factor receptor …

Epha2- And Hdac-Targeted Combination Therapy In Endometrial Cancer, Robiya Joseph, Santosh K Dasari, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mark Seungwook Kim, Sara Corvigno, Katherine Foster, Pahul Hanjra, Thanh Chung Vu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival …

Retrograde Type A　Acute Aortic Dissection With Cerebral Malperfusion Six Years After Thoracic Endovascular Aortic Repair, Hideki Sasaki, Yukihide Numata, Shinji Kamiya, Yoshiaki Sone, Miki Asano

Journal of the Saudi Heart Association

A 59-year-old male with prior thoracic endovascular aortic repair presented with altered mental status. Magnetic resonance imaging showed cerebral infarction, and subsequent computed tomography revealed acute type A aortic dissection and right carotid artery occlusion. He underwent total arch replacement with right carotid artery bypass. After successful intervention, he was transferred to a rehabilitation facility for further improvement.

Systolic Pulmonary Artery Pressure Thresholds Predictive Of Dyspnea On Stress Doppler Echocardiography In Mitral Stenosis, Saléha Lehachi, Fadila Daimellah, Saida Khelil, Zakia Bennoui, Djohar Hannoun, Youcef Laid, Rachid Mechmeche, Mohand Said Issad

Journal of the Saudi Heart Association

Background. On Stress Doppler Echocardiography (SDE) in mitral stenosis, the systolic pulmonary artery pressure (SPAP) threshold at peak exercise recommended by the guidelines as an indication for percutaneous mitral commissurotomy (PMC) used to be 60 mmHg. However, because of the paucity of studies, that threshold has been controversial. The Europeans stopped using the value in 2007, followed by the Americans in 2014.

Objective. Determine SPAP thresholds on SDE at peak exercise and post-exercise predictive of dyspnea as an indication for PMC in mitral stenosis.

Method and results. Three hundred mitral stenosis patients with a mitral valve area (MVA) ≤ 2 …

Fibrin Glue Acutely Blocks Distal Muscle Contraction After Confirmed Polyethylene Glycol Nerve Fusion: An Animal Study., Alec H Fisher, Parker H Johnsen, Andrew Simon, Cameron J Burns, Vineeth Romiyo, Elliot B Bodofsky, Sebastian Vega, David A Fuller

Cooper Medical School of Rowan University Departmental Research

BACKGROUND: Polyethylene glycol (PEG) is a synthetic, biodegradable, and hyperosmotic material promising in the treatment of acute peripheral nerve injuries. Our team set out to investigate the impact of fibrin glue upon PEG fusion in a rat model.

METHODS: Eighteen rats underwent sciatic nerve transection and PEG fusion. Electrophysiologic testing was performed to measure nerve function and distal muscle twitch. Fibrin glue was applied and testing repeated. Due to preliminary findings, fibrin glue was applied to an uncut nerve in five rodents and testing was conducted before and after glue application. Mann-Whitney U tests were used to compare median values …

Ai-Enhanced Detection Of Clinically Relevant Structural And Functional Anomalies In Mri: Traversing The Landscape Of Conventional To Explainable Approaches, Pegah Khosravi, Saber Mohammadi, Fatemeh Zahiri, Masoud Khodarahmi, Javad Zahiri

Publications and Research

Anomaly detection in medical imaging, particularly within the realm of magnetic resonance imaging (MRI), stands as a vital area of research with far-reaching implications across various medical fields. This review meticulously examines the integration of artificial intelligence (AI) in anomaly detection for MR images, spotlighting its transformative impact on medical diagnostics. We delve into the forefront of AI applications in MRI, exploring advanced machine learning (ML) and deep learning (DL) methodologies that are pivotal in enhancing the precision of diagnostic processes. The review provides a detailed analysis of preprocessing, feature extraction, classification, and segmentation techniques, alongside a comprehensive evaluation of …

Perceived Outcomes Of Periacetabular Osteotomy, Ryan Bialaszewski, John M. Gaddis, Bretton Laboret, Elizabeth Bergman, Edward P. Mulligan, Jenny Lacross, Adina Stewart, Joel Wells

School of Medicine Publications

Aims: Social media is a popular resource for patients seeking medical information and sharing experiences. periacetabular osteotomy (PAO) is the gold-standard treatment for symptomatic acetabular dysplasia with good long-term outcomes. However, little is known regarding the perceived outcomes of PAO on social media. The aims of this study were to describe the perceived outcomes following PAO using three social media platforms: Facebook, Instagram, and X (formerly known as Twitter).

Methods: Facebook, Instagram, and X posts were retrospectively collected from 1 February 2023. Facebook posts were collected from the two most populated interest groups: “periacetabular osteotomy” and “PAO Australia.” Instagram and …

Performance Of Automated Machine Learning In Predicting Outcomes Of Pneumatic Retinopexy, Arina Nisanova, Arefeh Yavary, Jordan Deaner, Ferhina Ali, Priyanka Gogte, Richard Kaplan, Kevin Chen, Eric Nudleman, Dilraj Grewal, Meenakashi Gupta, Jeremy Wolfe, Michael Klufas, Glenn Yiu, Iman Soltani, Parisa Emami-Naeini

Wills Eye Hospital Papers

PURPOSE: Automated machine learning (AutoML) has emerged as a novel tool for medical professionals lacking coding experience, enabling them to develop predictive models for treatment outcomes. This study evaluated the performance of AutoML tools in developing models predicting the success of pneumatic retinopexy (PR) in treatment of rhegmatogenous retinal detachment (RRD). These models were then compared with custom models created by machine learning (ML) experts.

DESIGN: Retrospective multicenter study.

PARTICIPANTS: Five hundred and thirty nine consecutive patients with primary RRD that underwent PR by a vitreoretinal fellow at 6 training hospitals between 2002 and 2022.

METHODS: We used 2 AutoML …

Bispecific Bcma/Cd24 Car-T Cells Control Multiple Myeloma Growth, Fumou Sun, Yan Cheng, Visanu Wanchai, Wancheng Guo, David Mery, Hongwei Xu, Dongzheng Gai, Eric Siegel, Clyde Bailey, Cody Ashby, Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Yupo Ma, Qing Yi, Robert Z Orlowski, Maurizio Zangari, Frits Van Rhee, Siegfried Janz, Gail Bishop, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing

Faculty, Staff and Student Publications

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell …

Effect Of Zwitterionic Additives On Solvation And Transport Of Sodium And Potassium Cations In (Ethylene Oxide)10: A Molecular Dynamics Simulation Study, Manh Tien Nguyen, Yuhua Duan, Qing Shao

Markey Cancer Center Faculty Publications

Sodium- (Na+) and potassium- (K+) ion batteries are cost-effective alternatives to lithium- ion (Li+) batteries due to the abundant sodium and potassium resources. Solid polymer electrolytes (SPEs) are essential for safer and more efficient Na+ and K+ batteries because they often exhibit low ionic conductivity at room temperature. While zwitterionic (ZW) materials enhance Li+ battery conductivity, their potential for Na+ and K+ transport in batteries remains unexplored. In this study, we investigated the effect of three ZW molecules (ChoPO4, i.e., 2-methacryloyloxyethyl phosphoryl- choline, ImSO3, i.e., sulfobetaine ethylimidazole, and ImCO2, i.e., carboxybetaine ethylimidazole) on the dissociation of Na+ and K+ coordination …

Induced Degradation Of Lineage-Specific Oncoproteins Drives The Therapeutic Vulnerability Of Small Cell Lung Cancer To Parp Inhibitors, Chiho Kim, Xu-Dong Wang, Zhengshuai Liu, Jianwei Hao, Shuai Wang, Peng Li, Zhenzhen Zi, Qing Ding, Seoyeon Jang, Jiwoong Kim, Yikai Luo, Kenneth E Huffman, Shreoshi Pal Choudhuri, Sofia Del Rio, Ling Cai, Han Liang, Benjamin J Drapkin, John D Minna, Yonghao Yu

Faculty, Staff and Student Publications

Although BRCA1/2 mutations are not commonly found in small cell lung cancer (SCLC), a substantial fraction of SCLC shows clinically relevant response to PARP inhibitors (PARPis). However, the underlying mechanism(s) of PARPi sensitivity in SCLC is poorly understood. We performed quantitative proteomic analyses and identified proteomic changes that signify PARPi responses in SCLC cells. We found that the vulnerability of SCLC to PARPi could be explained by the degradation of lineage-specific oncoproteins (e.g., ASCL1). PARPi-induced activation of the E3 ligase HUWE1 mediated the ubiquitin-proteasome system (UPS)-dependent ASCL1 degradation. Although PARPi induced a general DNA damage response in SCLC cells, this …

Microsurgical Clipping Of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation Of Perioperative Outcomes, Jennifer Sauvigny, Richard Drexler, Tobias Pantel, Franz Ricklefs, Joshua Catapano, John Wanebo, Michael Lawton, Aminaa Sanchin, Nils Hecht, Peter Vajkoczy, Kunal Raygor, Daniel Tonetti, Adib Abla, Kareem El Naamani, Stavropoula Tjoumakaris, Pascal Jabbour, Brian Jankowitz, Mohamed Salem, Jan-Karl Burkhardt, Arthur Wagner, Maria Wostrack, Jens Gempt, Bernhard Meyer, Michael Gaub, Justin Mascitelli, Philippe Dodier, Gerhard Bavinzski, Karl Roessler, Nico Stroh, Matthias Gmeiner, Andreas Gruber, Eberval Figueiredo, Antonio Carlos Samaia Da Silva Coelho, Anatoliy Bervitskiy, Egor Anisimov, Jamil Rzaev, Harald Krenzlin, Naureen Keric, Florian Ringel, Dougho Park, Mun-Chul Kim, Eleonora Marcati, Marco Cenzato, Linda Krause, Manfred Westphal, Lasse Dührsen, Thomas Sauvigny

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms.

METHODS: Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on …