Medical Specialties Commons^™

Early Estimate Of Nirsevimab Effectiveness For Prevention Of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season - New Vaccine Surveillance Network, October 2023-February 2024, Heidi L Moline, Ayzsa Tannis, Ariana P Toepfer, John V Williams, Julie A Boom, Janet A Englund, Natasha B Halasa, Mary Allen Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Marian G Michaels, Leila C Sahni, Eileen J Klein, Laura S Stewart, Elizabeth P Schlaudecker, Peter G Szilagyi, Jennifer E Schuster, Leah Goldstein, Samar Musa, Pedro A Piedra, Danielle M Zerr, Kristina A Betters, Chelsea Rohlfs, Christina Albertin, Dithi Banerjee, Erin R Mckeever, Casey Kalman, Benjamin R Clopper, Meredith L Mcmorrow, Fatimah S Dawood

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants agedtrials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, …

Variants In Zfx Are Associated With An X-Linked Neurodevelopmental Disorder With Recurrent Facial Gestalt\, James L Shepherdson, Katie Hutchison, Dilan Wellalage Don, George Mcgillivray, Tae-Ik Choi, Carolyn A Allan, David J Amor, Siddharth Banka, Donald G Basel, Laura D Buch, Deanna Alexis Carere, Renée Carroll, Jill Clayton-Smith, Ali Crawford, Morten Dunø, Laurence Faivre, Christopher P Gilfillan, Nina B Gold, Karen W Gripp, Emma Hobson, Alexander M Holtz, A Micheil Innes, Bertrand Isidor, Adam Jackson, Panagiotis Katsonis, Leila Amel Riazat Kesh, Genomics England Research Consortium;, Sébastien Küry, François Lecoquierre, Paul Lockhart, Julien Maraval, Naomichi Matsumoto, Julie Mccarrier, Josephine Mccarthy, Noriko Miyake, Lip Hen Moey, Andrea H Németh, Elsebet Østergaard, Rushina Patel, Kate Pope, Jennifer E Posey, Rhonda E Schnur, Marie Shaw, Elliot Stolerman, Julie P Taylor, Erin Wadman, Emma Wakeling, Susan M White, Lawrence C Wong, James R Lupski, Olivier Lichtarge, Mark A Corbett, Jozef Gecz, Charles M Nicolet, Peggy J Farnham, Cheol-Hee Kim, Marwan Shinawi

Duncan NRI Faculty and Staff Publications

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included …

Protein Biomarkers And Alternatively Methylated Cell-Free Dna Detect Early Stage Pancreatic Cancer, Roni Ben-Ami, Qiao-Li Wang, Jinming Zhang, Julianna G Supplee, Johannes F Fahrmann, Roni Lehmann-Werman, Lauren K Brais, Jonathan Nowak, Chen Yuan, Maureen Loftus, Ana Babic, Ehsan Irajizad, Tal Davidi, Aviad Zick, Ayala Hubert, Daniel Neiman, Sheina Piyanzin, Ofer Gal-Rosenberg, Amit Horn, Ruth Shemer, Benjamin Glaser, Natalia Boos, Kunal Jajoo, Linda Lee, Thomas E Clancy, Douglas A Rubinson, Kimmie Ng, John A Chabot, Fay Kastrinos, Michael Kluger, Andrew J Aguirre, Pasi A Jänne, Nabeel Bardeesy, Ben Stanger, Mark H O'Hara, Jacob Till, Anirban Maitra, Erica L Carpenter, Andrea J Bullock, Jeanine Genkinger, Samir M Hanash, Cloud P Paweletz, Yuval Dor, Brian M Wolpin

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed.

Design: To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites.

Results: Comparative methylome analysis identified nine loci that were differentially …

Maternal And Perinatal Health Research During Emerging And Ongoing Epidemic Threats: A Landscape Analysis And Expert Consultation, Mercedes Bonet, Magdalena Babinska, Pierre Buekens, Shivaprasad S Goudar, Beate Kampmann, Marian Knight, Dana Meaney-Delman, Smaragda Lamprianou, Flor Muñoz Rivas, Andy Stergachis, Cristiana M Toscano, Joycelyn Bhatia, Sarah Chamberlain, Usman Chaudhry, Jacqueline Mills, Emily Serazin, Hannah Short, Asher Steene, Michael Wahlen, Olufemi T Oladapo

Faculty, Staff and Students Publications

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner.

METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of …

Safety, Tolerability, And Dose-Limiting Toxicity Of Lacosamide In Patients With Painful Chronic Pancreatitis: Protocol For A Phase 1 Clinical Trial To Determine Safety And Identify Side Effects, Evan L Fogel, Jeffrey J Easler, Ying Yuan, Dhiraj Yadav, Darwin L Conwell, Santhi Swaroop Vege, Samuel Y Han, Walter Park, Vanessa Patrick, Fletcher A White

Faculty, Staff and Student Publications

Background: Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control.

Objective: In this phase 1 trial, we aim to determine the safety, …

One Form And Two Functions: Mbd Of Setdb2 Is A Protein-Interacting Domain, Jujun Zhou, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

In this issue of Structure, Mahana et al.1 present their structural characterization of an annotated methyl-CpG-binding domain (MBD) from the histone H3 lysine 9 methyltransferase SETDB2. This study reveals that, rather than binding DNA as previously hypothesized, this domain instead interacts with a cystine-rich domain from C11orf46, highlighting its involvement in protein-protein interactions.

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 …

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 …

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.

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 …

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" [...].

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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

Neuroscience Articles

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 …

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: …

Consensus-Based Development Of A Pediatric Echocardiography Complexity Score: Design, Rationale, And Results Of A Quality Improvement Collaborative, Sowmya Balasubramanian, Sunkyung Yu, Sarina K Behera, Aarti H Bhat, Joseph A Camarda, Nadine F Choueiter, Pei-Ni Jone, Leo Lopez, Shobha S Natarajan, David A Parra, Anitha Parthiban, Ritu Sachdeva, Shubhika Srivastava, Elif Seda Selamet Tierney

Faculty, Staff and Students Publications

BACKGROUND: The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score.

METHODS AND RESULTS: The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. …