Medical Specialties Commons^™

Tomivosertib Reduces Ectopic Activity In Dorsal Root Ganglion Neurons From Patients With Radiculopathy, Yan Li, Megan L Uhelski, Robert Y North, Juliet M Mwirigi, Claudio E Tatsui, Kathleen E Mcdonough, Juan P Cata, German Corrales, Greg Dussor, Theodore J Price, Patrick M Dougherty

Faculty, Staff and Student Publications

Spontaneous activity in dorsal root ganglion (DRG) neurons is a key driver of neuropathic pain in patients suffering from this largely untreated disease. While many intracellular signalling mechanisms have been examined in preclinical models that drive spontaneous activity, none have been tested directly on spontaneously active human nociceptors.

Using cultured DRG neurons recovered during thoracic vertebrectomy surgeries, we showed that inhibition of mitogen-activated protein kinase interacting kinase (MNK) with tomivosertib (eFT508, 25 nM) reversibly suppresses spontaneous activity in human sensory neurons that are likely nociceptors based on size and action potential characteristics associated with painful dermatomes within minutes of treatment. …

Social Vulnerability And Sickle Cell Disease Mortality In The Us, Jia Yi Tan, Boon Jian San, Yong-Hao Yeo, Kok Hoe Chan, Hamid S Shaaban, Daniel E Ezekwudo, Modupe Idowu

Faculty, Staff and Student Publications

Importance: Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies.

Objective: To investigate the association of SDOH with SCD mortality rates from 2016 to 2020.

Design, setting, and participants: This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into …

Angiotensin-(1-9) Retro-Enantiomer Peptide With Cardioprotective Activity, Yvo Flores, Gerald Zapata-Torres, Agustín Nuñez, Douglas J Matthies, Larissa Alemán, Carolina Hernández-Fuentes, Gina Sánchez, Eyleen Araya, Fanny Guzman, Zully Pedrozo, Salvador Guardiola, Mónica Varese, Ernest Giralt, Ivan Maslov, Mark Del Borgo, Robert E Widdop, Silvana Valdebenito, Eliseo A Eugenin, Mario Chiong, Joseph A Hill, María Paz Ocaranza, Marcelo J Kogan, Sergio Lavandero

Faculty, Staff and Student Publications

No abstract provided.

Prognostic Impact Of Notch1 Intracellular Domain, P63, And C-Myc In Lacrimal Gland Adenoid Cystic Carcinoma, Jiawei Zhao, Michelle D Williams, Mike Hernandez, Grace Kuang, Hila Goldberg, Janet Fan, Jing Ning, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

PURPOSE: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC).

METHODS: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC.

RESULTS: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none …

Rad21 Promotes Oncogenesis And Lethal Progression Of Prostate Cancer, Xiaofeng A Su, Konrad H Stopsack, Daniel R Schmidt, Duanduan Ma, Zhe Li, Paul A Scheet, Kathryn L Penney, Tamara L Lotan, Wassim Abida, Elise G Dearment, Kate Lu, Thomas Janas, Sofia Hu, Matthew G Vander Heiden, Massimo Loda, Monica Boselli, Angelika Amon, Lorelei A Mucci

Faculty, Staff and Student Publications

Higher levels of aneuploidy, characterized by imbalanced chromosome numbers, are associated with lethal progression in prostate cancer. However, how aneuploidy contributes to prostate cancer aggressiveness remains poorly understood. In this study, we assessed in patients which genes on chromosome 8q, one of the most frequently gained chromosome arms in prostate tumors, were most strongly associated with long-term risk of cancer progression to metastases and death from prostate cancer (lethal disease) in 403 patients and found the strongest candidate was cohesin subunit gene,

The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M Kurie

Faculty, Staff and Student Publications

No abstract provided.

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Segregation By Payer In Obstetrics And Gynecology Residency Ambulatory Care Sites, Kavita Vinekar, Neena Qasba, Hannah Reiser, Erika Banks, Kavita Arora, Brownsyne Edmonds, Karen George

Department of Obstetrics and Gynecology Faculty Papers

IMPORTANCE: Many teaching hospitals in the US segregate patients by insurance status, with resident clinics primarily composed of publicly insured or uninsured patients and faculty practices seeing privately insured patients. The prevalence of this model in obstetrics and gynecology residencies is unknown.

OBJECTIVES: To examine the prevalence of payer-based segregation in obstetrics and gynecology residency ambulatory care sites nationally and to compare residents' and program directors' perceptions of differences in quality of care between payer-segregated and integrated sites.

DESIGN, SETTING, AND PARTICIPANTS: This national survey study included all 6060 obstetrics and gynecology residents and 293 obstetrics and gynecology residency program …

Exoskeletal-Assisted Walking In Veterans With Paralysis: A Randomized Clinical Trial, Ann M Spungen, Ellen J Dematt, Kousick Biswas, Karen M Jones, Zhibao Mi, Amanda J Snodgrass, Kel Morin, Pierre K Asselin, Christopher M Cirnigliaro, Steven Kirshblum, Peter H Gorman, Lance L Goetz, Katherine Stenson, Kevin T White, Alice Hon, Sunil Sabharwal, B Jenny Kiratli, Doug Ota, Bridget Bennett, Joseph E Berman, Denis Castillo, Kenneth K Lee, Byron W Eddy, M Kristi Henzel, Michelle Trbovich, Sally A Holmes, Felicia Skelton, Michael Priebe, Stephen L Kornfeld, Grant D Huang, William A Bauman

Faculty, Staff and Students Publications

IMPORTANCE: Robotic exoskeletons leverage technology that assists people with spinal cord injury (SCI) to walk. The efficacy of home and community exoskeletal use has not been studied in a randomized clinical trial (RCT).

OBJECTIVE: To examine whether use of a wheelchair plus an exoskeleton compared with use of only a wheelchair led to clinically meaningful net improvements in patient-reported outcomes for mental and physical health.

DESIGN, SETTING, AND PARTICIPANTS: This RCT of veterans with SCI was conducted at 15 Veterans Affairs medical centers in the US from September 6, 2016, to September 27, 2021. Data analysis was performed from March …

Human Papillomavirus Vaccination And Human Papillomavirus-Related Cancer Rates, Victor Adekanmbi, Itunu Sokale, Fangjian Guo, Jessica Ngo, Thao N Hoang, Christine D Hsu, Abiodun Oluyomi, Abbey B Berenson

Faculty, Staff and Students Publications

IMPORTANCE: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs).

OBJECTIVE: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based …

Folate Metabolism And Risk Of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis From The Childhood Cancer And Leukemia International Consortium, Catherine Metayer, Logan G Spector, Michael E Scheurer, Soyoung Jeon, Rodney J Scott, Masatoshi Takagi, Jacqueline Clavel, Atsushi Manabe, Xiaomei Ma, Elleni M Hailu, Philip J Lupo, Kevin Y Urayama, Audrey Bonaventure, Motohiro Kato, Aline Meirhaeghe, Charleston W K Chiang, Libby M Morimoto, Joseph L Wiemels

Faculty, Staff and Students Publications

BACKGROUND: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

METHODS: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). …

Machine Learning To Enhance Electronic Detection Of Diagnostic Errors, Andrew J Zimolzak, Li Wei, Usman Mir, Ashish Gupta, Viralkumar Vaghani, Devika Subramanian, Hardeep Singh

Faculty, Staff and Students Publications

This cohort study examines whether machine learning (ML) can enhance the ability of electronic triggers to identify possible missed opportunities in diagnosis.

Risk Of Anxiety Disorders In Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: Men with prostate cancer (PC) may experience significant psychosocial distress from physical symptoms, treatment side effects, or fear of recurrence. However, little is known about the long-term risk of anxiety disorders in men with PC.

METHODS: A national cohort study was conducted of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched population-based control men in Sweden. Anxiety disorders were ascertained from nationwide outpatient and inpatient records through 2018. Cox regression was used to estimate hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses explored differences by PC treatment during 2005-2017. …

Glycemic Control In Diabetic Patients Improved Overall Lung Cancer Survival Across Diverse Populations, Wayne Y Wu, Brian Luke, Xiao-Cheng Wu, J Jack Lee, Yong Yi, Samuel C Okpechi, Barry Gause, Paras Mehta, Steven I Sherman, Augusto Ochoa, Ethan Dmitrovsky, Xi Liu

Faculty, Staff and Student Publications

Background: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity.

Methods: The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed …

Scintruler: Guiding The Integration Of Multiple Single-Cell Rna-Seq Datasets With A Novel Statistical Metric, Yue Lyu, Steven H Lin, Hao Wu, Ziyi Li

Faculty, Staff and Student Publications

Motivation: The growing number of single-cell RNA-seq (scRNA-seq) studies highlights the potential benefits of integrating multiple datasets, such as augmenting sample sizes and enhancing analytical robustness. Inherent diversity and batch discrepancies within samples or across studies continue to pose significant challenges for computational analyses. Questions persist in practice, lacking definitive answers: Should we use a specific integration method or opt for simply merging the datasets during joint analysis? Among all the existing data integration methods, which one is more suitable in specific scenarios?

Result: To fill the gap, we introduce SCIntRuler, a novel statistical metric for guiding the integration of …

Setrusumab For The Treatment Of Osteogenesis Imperfecta: 12-Month Results From The Phase 2b Asteroid Study, Francis H Glorieux, Bente Langdahl, Roland Chapurlat, Suzanne Jan De Beur, Vernon Reid Sutton, Kenneth E S Poole, Kathryn M Dahir, Eric S Orwoll, Bettina M Willie, Nicholas Mikolajewicz, Elizabeth Zimmermann, Seyedmahdi Hosseinitabatabaei, Michael S Ominsky, Chris Saville, James Clancy, Alastair Mackinnon, Arun Mistry, Muhammad K Javaid

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or …

Factors Associated With Recanalization And Reintervention Following Below Knee Polidocanol Endovenous Microfoam Ablation For Great Saphenous And Small Saphenous Veins, John Fang, Christian Fang, Andy Moyal, Enrico Ascher, Anil Hingorani, Natalie Marks

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Polidocanol endovenous microfoam (PEM) has been used to treat lower extremity venous reflux for almost one decade with specific advantages for below knee (BK) truncal veins where thermal ablation poses a risk of injury to adjacent nerves. The current literature of the BK segment often examines short-term outcomes with modest sample sizes. We aim to identify factors associated with recanalization and reintervention in this subset of patients.

METHODS: We performed a retrospective study of a prospectively maintained database of patients from a single institution who underwent 1% PEM ablation for BK great saphenous vein (GSV) and small saphenous vein …

A Comparison Of The Safety And Efficacy Of Tapinarof And Roflumilast Topical Therapies In The Management Of Mild-To-Moderate Plaque Psoriasis, Hira Ghani, Alicia Podwojniak, Isabella J Tan, Aarushi K Parikh, Bianca Sanabria, Babar Rao

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.

MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.

RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed …

Low-Acuity Pediatric Emergency Department Utilization, Lisa Ziemnik, Noah Parker, Kyra Bufi, Kristen Waters, Jacob Almeda, Adrienne Stolfi

Medical Education Faculty Publications

Objectives: Proper emergency department (ED) utilization is a hallmark of population health. Emergency department overcrowding due to nonurgent visits causes increased stress to healthcare staff, higher costs, and longer wait times for more urgent cases. This study sought to better understand post pandemic reasons caregivers have when bringing in their children for nonurgent visits and devise effective interventions to improve caregiver choice for non-ED care for nonurgent conditions.

Methods: Surveys were conducted at an urban pediatric hospital for Emergency Severity Index (ESI) level 3 to 5 visits. A total of 602 surveys were completed with 8 being excluded from analysis. …

Competency-Based Medical Education And The Education Continuum: Establishing A Framework For Lifelong Learning, Ann E. Burke, Daniel J. Sklansky, Hilary M. Haftel, Andrew Mitchell, Keith J. Mann

Pediatrics Faculty Publications

Competency Based Medical Education (CBME) is built on the concept that the competencies of learners, both graduates and practicing physicians, should ensure they are ready to meet the ever-changing healthcare needs of patients.1, 2, 3 Education outcomes in a CBME system are defined based on the needs of patients, and in healthy CBME systems, there is a paradigm shift from a focus on process and teachers to outcomes and learners.2,4 CBME should occur across the continuum of one's career, from undergraduate medical education through retirement. Furthermore, learners must be accustomed to driving their own educational processes.4,5 This learner-centered perspective requires …

Transvenous Tissue Sampling In The Diagnosis Of Intravascular Neoplasm., Christopher J Neely, Christopher M Huff, Andrew C Gordon, Raghu Kolluri, Kush R Desai

Heart and Vascular Articles

No abstract provided.

Predictors Of Outcome And Symptomatic Intracranial Hemorrhage In Acute Basilar Artery Occlusions: Analysis Of The Pc-Search Thrombectomy Registry., Adam T Mierzwa, Ashley Nelson, Sami Al Kasab, Santiago Ortega Gutierrez, Juan Vivanco-Suarez, Mudassir Farooqui, Ashutosh P Jadhav, Shashvat Desai, Gabor Toth, Anas Alrohimi, Thanh N Nguyen, Piers Klein, Mohamad Abdalkader, Hisham Salahuddin, Aditya Pandey, Zachary Wilseck, Sravanthi Koduri, Niraj Vora, Nameer Aladamat, Khaled Gharaibeh, Ehad Afreen, Hisham Al-Hajala, Julie Shawver, Syed Zaidi, Mouhammad Jumaa

Neuroscience Articles

INTRODUCTION: Recent randomized controlled trials demonstrated superiority of mechanical thrombectomy compared to medical therapy in acute basilar artery occlusions, however, little data is available to guide clinicians in functional prognosis and risk stratification.

PATIENTS AND METHODS: Data from the retrospectively established PC-SEARCH Thrombectomy registry, which included patients with basilar artery occlusion from eight sites from January 2015 to December 2021, was interrogated. Outcomes were dichotomized into 90-day favorable (mRS ⩽ 3) and unfavorable (mRS > 3). Multivariate logistic regression analysis was performed with respect to the outcome groups and were adjusted for potential confounding baseline characteristics.

RESULTS: Four-hundred-forty-four patients were included …

Ataxia Telangiectasia And Rad3-Related (Atr) Inhibitor Camonsertib Dose Optimization In Patients With Biomarker-Selected Advanced Solid Tumors (Tresr Study), Elisa Fontana, Ezra Rosen, Elizabeth K Lee, Martin Højgaard, Niharika B Mettu, Stephanie Lheureux, Benedito A Carneiro, Gregory M Cote, Louise Carter, Ruth Plummer, Devalingam Mahalingam, Adrian J Fretland, Joseph D Schonhoft, Ian M Silverman, Marisa Wainszelbaum, Yi Xu, Danielle Ulanet, Maria Koehler, Timothy A Yap

Faculty, Staff and Student Publications

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus, dose and schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety, tolerability, and antitumor efficacy of 3 camonsertib monotherapy dosing regimens were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on, 4 days off (160 3/4; the preliminary recommended Phase II dose [RP2D]) and two step-down groups of …

Identification Of Hypoxia-Alcamhigh Macrophage- Exhausted T Cell Axis In Tumor Microenvironment Remodeling For Immunotherapy Resistance, Zhenzhen Xun, Huanran Zhou, Mingyi Shen, Yao Liu, Chengcao Sun, Yanhua Du, Zhou Jiang, Liuqing Yang, Qing Zhang, Chunru Lin, Qingsong Hu, Youqiong Ye, Leng Han

Faculty, Staff and Student Publications

Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM

Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart

Faculty, Staff and Student Publications

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks …

Chemical Screening By Time-Resolved X-Ray Scattering To Discover Allosteric Probes, Chris A Brosey, Todd M Link, Runze Shen, Davide Moiani, Kathryn Burnett, Greg L Hura, Darin E Jones, John A Tainer

Faculty, Staff and Student Publications

Drug discovery relies on efficient identification of small-molecule leads and their interactions with macromolecular targets. However, understanding how chemotypes impact mechanistically important conformational states often remains secondary among high-throughput discovery methods. Here, we present a conformational discovery pipeline integrating time-resolved, high-throughput small-angle X-ray scattering (TR-HT-SAXS) and classic fragment screening applied to allosteric states of the mitochondrial import oxidoreductase apoptosis-inducing factor (AIF). By monitoring oxidized and X-ray-reduced AIF states, TR-HT-SAXS leverages structure and kinetics to generate a multidimensional screening dataset that identifies fragment chemotypes allosterically stimulating AIF dimerization. Fragment-induced dimerization rates, quantified with time-resolved SAXS similarity analysis (k

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

Premalignant Progression In The Lung: Knowledge Gaps And Novel Opportunities For Interception Of Non-Small Cell Lung Cancer An Official American Thoracic Society Research Statement, Seyed Javad Moghaddam, Rajkumar Savai, Ramin Salehi-Rad, Shreoshi Sengupta, Michael N Kammer, Pierre Massion, Jennifer E Beane, Edwin J Ostrin, Carmen Priolo, Meredith A Tennis, Laura P Stabile, Alison K Bauer, Catherine R Sears, Eva Szabo, M Patricia Rivera, Charles A Powell, Humam Kadara, Brendan J Jenkins, Steven M Dubinett, A Mcgarry Houghton, Carla F Kim, Robert L Keith

Faculty, Staff and Student Publications

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the …

A Pilot Study Of The Cd38 Antagonist Daratumumab In Patients With Metastatic Renal Cell Carcinoma Or Muscle-Invasive Bladder Cancer, Matthew T Campbell, Amishi Y Shah, Pavlos Msaouel, Nizar M Tannir, Arlene O Siefker-Radtke, Ashish M Kamat, Neema Navai, Colin P N Dinney, Priya Rao, Charles C Guo, Rahul A Sheth, Aradhana M Venkatesan, Rebecca S Tidwell, Shalini S Yadav, Aidi Gu, Hong Chen, Marc Macaluso, Fei Duan, Sreyashi Basu, Sonali Jindal, Padmanee Sharma

Faculty, Staff and Student Publications

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring …

Emergency Department Slit Lamp Interdisciplinary Training Via Longitudinal Assessment In Medical Practice, Samara Hamou, Shayan Ghiaee, Christine Chung, Maureen Lloyd, Kelly Khem, Xiao Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Eye emergencies make up nearly 3% of US emergency department (ED) visits. While emergency physicians (EP) should diagnose and treat these ophthalmologic emergencies, many trainees report limited ocular exposure and insufficient training throughout their residency to confidently conduct a thorough slit-lamp exam.

METHODS: We created an interdisciplinary, simulation-based mastery learning (SBML) curriculum to teach emergency attending physicians how to operate the slit lamp with multimodal learning methodology at a tertiary academic center. The EPs first demonstrate their initial slit-lamp competency with a 20-item checklist, and they then review the necessary curricular content to pass their independent readiness test before …