Medical Specialties Commons^™

Case Of Rosai Dorfman Disease In A Patient With Newly Diagnosed Hodgkin Lymphoma, Liza Salloum, Jennifer Rojas Huen, Ricardo Serna, Alisha Valdez

Research Symposium

Background: Rosai Dorfman Disease (RDD, also known as sinus histiocytosis with massive lymphadenopathy) is a rare non-Langerhans cell histiocytosis, classified into nodal (classic) and extranodal disease. Most patients present with non-tender cervical lymphadenopathy, although other sites including the inguinal and axillary regions have been reported. Extranodal disease (~43% of cases) can involve any organ system. RDD is more common in children, but cases have been reported in patients in their 70s. The prognosis of nodal RDD can correlate with the number of nodal groups involved. Many cases can be managed only with observation, although surgery, chemotherapy, corticosteroids, and immunomodulators have …

Baclofen Induced Excessive Perspiration; A Case Report, Othman Farahneh, Lois C. Akpati, Miguel Alvarez Silva

Research Symposium

This case report highlights an unexpected side effect of Baclofen, a well-known medication, excessive sweating, a rare occurrence not typically associated with the drug. The patient, a 63-year-old woman, experienced persistent sweating despite initial attributions to postmenopausal symptoms and subsequent medication adjustments. Extensive testing revealed an association between Baclofen use and the symptoms, which resolved upon discontinuation of the drug.

The significance of this case lies in drawing attention to the underreported side effects of excessive sweating linked to Baclofen, emphasizing the importance of considering medication-related effects even with established drugs. The report urges increased awareness among healthcare professionals, addressing …

An Unusual Presentation Of The Severe Hypothyroidism Presenting As Shortness Of Breath, Shreel H. Patel, Kashif Ali, Eunbee Cho, Fatimah Bello, Andres Suarez Parraga, Alcibiades Fleires

Research Symposium

Background: Hypothyroidism is defined as failure of the thyroid gland to produce sufficient thyroid hormone to meet the metabolic demands of the body. Untreated hypothyroidism can contribute to hypertension, dyslipidemia, infertility, cognitive impairment, and neuromuscular dysfunction. It may occur as a result of primary gland failure or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland. Primary gland failure can result from the congenital abnormalities, autoimmune destruction, iodine deficiency, and infiltrative diseases. Patients can clinically present with weight gain, cold intolerance, depression, muscle fatigue, poor concentration, and menstrual irregularities. The best laboratory test for the thyroid assessment is serum …

A True Bloody Emergency: An Unusual Case Of Thrombotic Thrombocytopenic Purpura, Joshua M. Ninan

Research Symposium

Background: Thrombotic thrombocytopenic purpura (TTP) is a primary thrombotic microangiopathy that is classically characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Although rare with an annual incidence of 3.7 cases per one million adults, it is considered a true hematological emergency due to its fatality rate of almost 100% if appropriate treatment is not initiated immediately. This makes it vitally important to identify and treat patients with TTP, a task that becomes unusually challenging in the absence of the disorder’s other characteristically diagnostic clinical features such as mucosal bleeding, fever, or presence of schistocytes.

Case Presentation: A 30-year-old gentleman with …

Evaluating The Management Trends For Priapism And Assessing The Risk Of Priapism After In-Office Intracavernosal Injections: A Cross-Sectional Analysis, Joon Yau Leong, Zachary J. Prebay, David Ebbott, Michael Li, Paul H. Chung

Department of Urology Faculty Papers

We describe the management trends of patients suffering from any priapism and evaluate the risks of developing priapism after intracavernosal injections (ICI) performed in office. We queried TriNetX for two separate male adult cohorts - those presenting with any priapism based on International Classification of Disease code, N48.3 (priapism) and those who underwent ICI in office based on Current Procedural Terminology code, 54235 (injection of corpora cavernosa with pharmacologic agent[s]). We evaluated treatment options for these patients after any priapism and described demographic risks for developing priapism after ICI performed in office. There were 17,545 priapism encounters and 26,104 usages …

A Rare Occurrence Of Digital Fibromyxoma To The Hallux Distal Phalanx, Heather V. Tran, Nikita Gambhir, Craig J. Verdin, Luis Caporusso, Stephanie N. Campbell

School of Podiatric Medicine Publications

A paucity of literature exists for superficial acral fibromyxoma, which typically affects the acral regions of the hands and feet. Because of its indolent nature and clinical mimicry of other ungual and periungual tumors, delays in diagnosis are common. This report aims to augment our understanding of this pathology and improve recognition for prompt diagnosis, as well as provide an addition to the literature.

Increased Hif-2Α Activity In The Nucleus Pulposus Causes Intervertebral Disc Degeneration In The Aging Mouse Spine, Shira N Johnston, Maria Tsingas, Rahatul Ain, Ruteja A Barve, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Hypoxia-inducible factors (HIFs) are essential to the homeostasis of hypoxic tissues. Although HIF-2α, is expressed in nucleus pulposus (NP) cells, consequences of elevated HIF-2 activity on disc health remains unknown. We expressed HIF-2α with proline to alanine substitutions (P405A; P531A) in the Oxygen-dependent degradation domain (HIF-2αdPA) in the NP tissue using an inducible, nucleus pulposus-specific K19^CreERT allele to study HIF-2α function in the adult intervertebral disc. Expression of HIF-2α in NP impacted disc morphology, as evident from small but significantly higher scores of degeneration in NP of 24-month-old K19^CreERT; HIF-2α^dPA (K19-dPA) mice. Noteworthy, comparisons of grades …

Single-Cell Cd4 And Cd8 T-Cell Secretome Profiling Reveals Temporal And Niche Differences In Acute Myeloid Leukemia Following Immune Checkpoint Blockade Therapy, Jessica L Root, Poonam N Desai, Christopher Ly, Bofei Wang, Fatima Zahra Jelloul, Jing Zhou, Sean Mackay, Mansour Alfayez, Jairo Matthews, Sherry Pierce, Patrick K Reville, Naval Daver, Hussein A Abbas

Faculty, Staff and Student Publications

UNLABELLED: Acute myeloid leukemia (AML) is a heterogeneous malignancy of the blood primarily treated with intensive chemotherapy. The allogeneic T-cell antileukemic activity via donor lymphocyte infusions and stem cell transplantation suggests a potential role for checkpoint blockade therapy in AML. While clinical trials employing these treatments have fallen short of expected results, a deeper exploration into the functional states of T cells in AML could bridge this knowledge gap. In this study, we analyzed the polyfunctional activity of T cells in a cohort of patients with relapsed/refractory (RelRef) AML treated on the clinical trial (ClinicalTrials.gov identifier: NCT02397720) of combination therapy …

Chimeric Oncolytic Adenovirus Evades Neutralizing Antibodies From Human Patients And Exhibits Enhanced Anti-Glioma Efficacy In Immunized Mice, Dong Ho Shin, Hong Jiang, Andrew G Gillard, Debora Kim, Xuejun Fan, Sanjay K Singh, Teresa T Nguyen, Sagar S Sohoni, Andres R Lopez-Rivas, Akhila Parthasarathy, Chibawanye I Ene, Joy Gumin, Frederick F Lang, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent …

Inhibition Of Mer Proto-Oncogene Tyrosine Kinase By An Antisense Oligonucleotide Enhances Treatment Efficacy Of Immunoradiotherapy, Yun Hu, Alexey Revenko, Hampartsoum Barsoumian, Genevieve Bertolet, Natalie Wall Fowlkes, Hadi Maazi, Morgan Maureen Green, Kewen He, Duygu Sezen, Tiffany A Voss, Claudia S Kettlun Leyton, Fatemeh Masrorpour, Zahid Rafiq, Nahum Puebla-Osorio, Carola Leuschner, Robert Macleod, Maria Angelica Cortez, James W Welsh

Faculty, Staff and Student Publications

Background: The combination of radiotherapy and immunotherapy (immunoradiotherapy) has been increasingly used for treating a wide range of cancers. However, some tumors are resistant to immunoradiotherapy. We have previously shown that MER proto-oncogene tyrosine kinase (MerTK) expressed on macrophages mediates resistance to immunoradiotherapy. We therefore sought to develop therapeutics that can mitigate the negative impact of MerTK. We designed and developed a MerTK specific antisense oligonucleotide (ASO) and characterized its effects on eliciting an anti-tumor immune response in mice.

Methods: 344SQR cells were injected into the right legs on day 0 and the left legs on day 4 of 8-12 …

Immuno-Molecular Targeted Therapy Use And Survival Benefit In Patients With Stage Ivb Cervical Carcinoma In Commission On Cancer, Collin A Sitler, Chunqiao Tian, Chad A Hamilton, Michael T Richardson, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christina Washington, Nicole P Chappell, Ann H Klopp, Craig D Shriver, Christopher M Tarney, Nicholas W Bateman, Thomas P Conrads, George Larry Maxwell, Neil T Phippen, Kathleen M Darcy

Faculty, Staff and Student Publications

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials.

METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates.

RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use …

Caldendrin Is A Repressor Of Piezo2 Channels And Touch Sensation In Mice, Josue A Lopez, Luis O Romero, Wai-Lin Kaung, J Wesley Maddox, Valeria Vásquez, Amy Lee

Faculty, Staff and Student Publications

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged …

Transcriptomic, Proteomic, And Genomic Mutational Fraction Differences Based On Hpv Status Observed In Patient-Derived Xenograft Models Of Penile Squamous Cell Carcinoma, Niki M Zacharias, Luis Segarra, Keiko Akagi, Natalie Wall Fowlkes, Huiqin Chen, Angelita Alaniz, Carolyn De La Cerda, Pedro Pesquera, Yuanxin Xi, Jing Wang, Jad Chahoud, Xin Lu, Priya Rao, Magaly Martinez-Ferrer, Curtis A Pettaway

Faculty, Staff and Student Publications

Simple Summary

Penile cancer is a rare but aggressive cancer. After it metastasizes, the median survival time is less than 12 months. The overall response rate to common first-line combination chemotherapy treatments is approximately 50%. There is an urgent need in advanced-penile-cancer treatment to find novel therapies that would generate better response rates than standard chemotherapy thus far and have less toxicity. Partially due to its rarity, there are few animal models and cell lines of penile cancer. We report on the generation of seven penile cancer animal models that were created by directly implanting human tumor tissue into immunocompromised …

Rational Prescribing Of Pancreatic Enzymes For Patients With Pancreatic Cancer, Mary Acelle G Garcia, Syed Imam, Ursula K Braun, Leanne K Jackson

Center for Medical Ethics and Health Policy Staff Publications

Most patients with pancreatic cancer at some point present with symptoms related to exocrine pancreatic insufficiency (EPI). These include diarrhea, abdominal bloating, indigestion, steatorrhea, weight loss, and anorexia. Even though up to 80% of pancreatic cancer patients eventually present with symptoms related to exocrine pancreatic insufficiency, only 21% are prescribed pancreatic enzyme replacement therapy (PERT). Its effectiveness is also highly dependent on its proper timing of administration, and patients must be thoroughly educated about this. The impact of symptoms of EPI can lead to poorer overall well-being. Pharmacists play a crucial role in properly educating patients on the correct use …

A Systematic Review Of Naldemedine And Naloxegol For The Treatment Of Opioid-Induced Constipation In Cancer Patients, Ursula K Braun, Leanne K Jackson, Mary A Garcia, Syed N Imam

Center for Medical Ethics and Health Policy Staff Publications

Background: Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients.

Objective: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients.

Methods: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients.

Results: Only three prospective randomized, double-blind, placebo-controlled clinical trials for …

Geographic Distribution Of Human Infections With Zoonotic Ancylostoma Ceylanicum And Anthropophilic Hookworms In Ecuador: A Retrospective Analysis Of Archived Stool Samples, Dayana Aguilar-Rodríguez, Victor Seco-Hidalgo, Andrea Lopez, Natalia Romero-Sandoval, Manuel Calvopiña, Angel Guevara, Lucy Baldeón, Alejandro Rodríguez, Rojelio Mejia, Thomas B Nutman, William J Sears, Philip J Cooper

Faculty, Staff and Students Publications

Zoonotic human infections with Ancylostoma ceylanicum have recently been reported in the Americas. We used archived human stool samples to study the geographic distribution of human infections with A. ceylanicum and anthropophilic hookworms in different geoclimatic regions (coastal, Andean, and Amazon) of Ecuador. We analyzed retrospectively archived human stool samples from five studies previously screened for hookworm infection by microscopy, of which four included hookworm-positive samples only and one involved hookworm-negative samples to increase geographic distribution of sampling. Stools were analyzed using multi-parallel quantitative polymerase chain reaction (qPCR) assays to detect Necator americanus, Ancylostoma duodenale, A. ceylanicum, Ascaris lumbricoides, Trichuris …

Inactivation Of Adenosine Receptor 2a Suppresses Endothelial-To-Mesenchymal Transition And Inhibits Subretinal Fibrosis In Mice, Qiuhua Yang, Yongfeng Cai, Qian Ma, Albert Xiong, Peishan Xu, Zhidan Zhang, Jiean Xu, Yaqi Zhou, Zhiping Liu, Dingwei Zhao, John Asara, Wei Li, Huidong Shi, Ruth B Caldwell, Akrit Sodhi, Yuqing Huo

Faculty, Staff and Students Publications

Anti–vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury–induced CNV or mice with a deficiency in the …

Correction: Jiménez-Ortigosa Et Al Cryo-Electron Tomography Of Candida Glabrata Plasma Membrane Proteins J Fungi 2021, 7, 120, Cristina Jiménez-Ortigosa, Jennifer Jiang, Muyuan Chen, Xuyuan Kuang, Kelley R Healey, Paul Castellano, Nikpreet Boparai, Steven J Ludtke, David S Perlin, Wei Dai

Faculty, Staff and Students Publications

The authors wish to update the article title to "Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins" [...].

Enhancing Prognostic Power In Multiple Myeloma Using A Plasma Cell Signature Derived From Single-Cell Rna Sequencing, Jian-Rong Li, Shahram Arsang-Jang, Yan Cheng, Fumou Sun, Anita D'Souza, Binod Dhakal, Parameswaran Hari, Quillan Huang, Paul Auer, Yong Li, Raul Urrutia, Fenghuang Zhan, John D Shaughnessy, Siegfried Janz, Jing Dong, Chao Cheng

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum …

Catatonia As A Result Of A Traumatic Brain Injury, Jessica Berthelot, Jacob Cambre, Madeline Erwin, Jennifer Phan

School of Medicine Faculty Publications

Catatonia is a neuropsychiatric syndrome typically marked by disturbances in motor activity, speech, and behavior. It has historically been associated with psychiatric illness, but acute medical illness, neurocognitive disorders, and neurodevelopmental disorders can cause catatonia as well. Catatonia is likely underrecognized and underdiagnosed in the general medical hospital, despite high risks of morbidity and mortality and the availability of rapidly effective treatment. Here, we present a case of catatonia secondary to traumatic brain injury that responded to lorazepam after a delayed diagnosis. A young male patient who was incarcerated and assaulted was sent to the emergency department multiple times for …

Motivational Interviewing Skills Practice Enhanced With Artificial Intelligence, Paul J. Hershberger, Yong Pei, Dean A. Bricker, Timothy N. Crawford, Ashutosh Shivakumar, Angie Castle, Katharine Conway, Raveendra Medaramitta, Maria Rechtin, Josephine F. Wilson

Family Medicine Faculty Publications

Background: Finding time in the medical curriculum to focus on motivational interviewing (MI) training is a challenge in many medical schools. We developed a software-based training tool, “Real-time Assessment of Dialogue in Motivational Interviewing” (ReadMI), that aims to advance the skill acquisition of medical students as they learn the MI approach. This human-artificial intelligence teaming may help reduce the cognitive load on a training facilitator. Methods: During their Family Medicine clerkship, 125 third-year medical students were scheduled in pairs to participate in a 90-minute MI training session, with each student doing two role-plays as the physician. Intervention group students received …

Muc20 Regulated By Extrachromosomal Circular Dna Attenuates Proteasome Inhibitor Resistance Of Multiple Myeloma By Modulating Cuproptosis, Xiaobin Wang, Yingqing Shi, Hua Shi, Xiaoyu Liu, Aijun Liao, Zhuogang Liu, Robert Z Orlowski, Rui Zhang, Huihan Wang

Faculty, Staff and Student Publications

BACKGROUND: Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation.

METHODS: We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay.

RESULTS: …

Hypertension In Pregnancy Among Immigrant And Swedish Women: A Cohort Study Of All Pregnant Women In Sweden, Per Wändell, Casey Crump, Xinjun Li, Nouha Saleh Stattin, Axel C Carlsson, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND: Little is known about risks of hypertensive disorders of pregnancy in both first- and second-generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first- and second-generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy.

METHODS AND RESULTS: A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the total Population Register. We used Cox regression analysis to compute hazard …

Potential Protein Signatures For Recurrence Prediction Of Ischemic Stroke, Chengyi Zhang, Yang Liu, Huimin Zhu, Xinying Huang, Cang Guo, Si Cheng, Meng Yuan, Yong Jiang, Xia Meng, S Claiborne Johnston, Yongjun Wang, Wei-Na Jin, Fu-Dong Shi

Faculty, Staff and Student Publications

Background: Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence.

Methods and results: We conducted a nested case-control study using a hospital-based cohort from the Third China National Stroke Registry selecting 214 age- and sex-matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data-independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large-artery atherosclerosis (Causative Classification of Ischemic Stroke …

Endovascular Thrombectomy For Large Ischemic Stroke Across Ischemic Injury And Penumbra Profiles, Amrou Sarraj, Ameer E Hassan, Michael G Abraham, Santiago Ortega-Gutierrez, Scott E Kasner, Muhammad Shazam Hussain, Michael Chen, Leonid Churilov, Hannah Johns, Clark W Sitton, Vignan Yogendrakumar, Felix C Ng, Deep K Pujara, Spiros Blackburn, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Andrew Cheung, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Chirag D Gandhi, Fawaz Al-Mufti, Natalia Pérez De La Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Faisal Al Shaibi, Gabor Toth, Mohammad A Abdulrazzak, Gagan Sharma, Abhishek Ray, Jeffrey Sunshine, Amanda Opaskar, Kelsey R Duncan, Wei Xiong, Edgar A Samaniego, Laith Maali, Colleen G Lechtenberg, Arturo Renú, Nirav Vora, Thanh Nguyen, Johanna T Fifi, Stavropoula I Tjoumakaris, Pascal Jabbour, Georgios Tsivgoulis, Vitor Mendes Pereira, Maarten G Lansberg, Michael Degeorgia, Cathy A Sila, Nicholas Bambakidis, Michael D Hill, Stephen M Davis, Lawrence Wechsler, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell

Faculty, Staff and Student Publications

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.

Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.

Design, setting, and participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 …

Unraveling The Intraday Variations In The Tear Fluid Proteome, Garrett Jones, Jeremy Altman, Saleh Ahmed, Tae Jin Lee, Wenbo Zhi, Shruti Sharma, Ashok Sharma

Faculty, Staff and Student Publications

PURPOSE: Tear fluid is a complex and dynamic biological fluid that plays essential roles in maintaining ocular homeostasis and protecting against the external environment. Owing to the small sample volume, studying the tear proteome is challenging. However, advances in high-resolution mass spectrometry have expanded tear proteome profiling, revealing >500 unique proteins. Tears are emerging as a noninvasive source of biomarkers for both ocular and systemic diseases; nevertheless, intraday variability of proteins in tear fluid remains questionable. This study investigates intraday variations in the tear fluid proteome to identify stable proteins that could act as candidate biomarkers.

METHODS: Tear samples from …

Sex Differences In Revascularization, Treatment Goals, And Outcomes Of Patients With Chronic Coronary Disease: Insights From The Ischemia Trial, Harmony R Reynolds, Derek D Cyr, C Noel Bairey Merz, Leslee J Shaw, Bernard R Chaitman, William E Boden, Karen P Alexander, Yves D Rosenberg, Sripal Bangalore, Gregg W Stone, Claes Held, John Spertus, Kaatje Goetschalckx, Olga Bockeria, Jonathan D Newman, Jeffrey S Berger, Ahmed Elghamaz, Renato D Lopes, James K Min, Daniel S Berman, Michael H Picard, Raymond Y Kwong, Robert A Harrington, Boban Thomas, Sean M O'Brien, David J Maron, Judith S Hochman, Ischemia Research Group

Faculty, Staff and Student Publications

BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.

METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for …

High Clinical Exome Sequencing Diagnostic Rates And Novel Phenotypic Expansions For Nonisolated Microphthalmia, Anophthalmia, And Coloboma, Bhavana Kunisetty, Bailey A Martin-Giacalone, Xiaonan Zhao, Pamela N Luna, Brian P Brooks, Robert B Hufnagel, Chad A Shaw, Jill A Rosenfeld, A J Agopian, Philip J Lupo, Daryl A Scott

Faculty, Staff and Student Publications

PURPOSE: A molecular diagnosis is only made in a subset of individuals with nonisolated microphthalmia, anophthalmia, and coloboma (MAC). This may be due to underutilization of clinical (whole) exome sequencing (cES) and an incomplete understanding of the genes that cause MAC. The purpose of this study is to determine the efficacy of cES in cases of nonisolated MAC and to identify new MAC phenotypic expansions.

METHODS: We determined the efficacy of cES in 189 individuals with nonisolated MAC. We then used cES data, a validated machine learning algorithm, and previously published expression data, case reports, and animal models to determine …

Eef1a2 Promotes Pten-Gsk3Β-Scf Complex-Dependent Degradation Of Aurora Kinase A And Is Inactivated In Breast Cancer, Warapen Treekitkarnmongkol, Luisa M Solis, Deivendran Sankaran, Mihai Gagea, Pankaj K Singh, Ragini Mistry, Tristian Nguyen, Kazuharu Kai, Jiajun Liu, Kaori Sasai, Yoshimi Jitsumori, Jianwen Liu, Norio Nagao, Fabio Stossi, Michael A Mancini, Ignacio I Wistuba, Alastair M Thompson, Jonathan M Lee, Juan Cadiñanos, Kwong-Kwok Wong, Catherine M Abbott, Aysegul A Sahin, Suyu Liu, Hiroshi Katayama, Subrata Sen

Faculty, Staff and Student Publications

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination and degradation of the mitosis-promoting Aurora kinase A in the S and G2 phases of the cell cycle. eEF1A2 bridged the interactions between the SKP1-CUL1-FBXW7 (SCF) ubiquitin …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of