Medical Specialties Commons^™

Potential Value Of A Rapid Syndromic Multiplex Pcr For The Diagnosis Of Native And Prosthetic Joint Infections: A Real-World Evidence Study, Stéphanie Pascual, Brooklyn Noble, Nusreen Ahmad-Saeed, Catherine Aldridge, Simone Ambretti, Sharon Amit, Rachel Annett, Shaan Ashk O'Shea, Anna Maria Barbui, Gavin Barlow, Lucinda Barrett, Mario Berth, Alessandro Bondi, Nicola Boran, Sara E Boyd, Catarina Chaves, Martin Clauss, Peter Davies, Ileana T Dianzo-Delgado, Jaime Esteban, Stefan Fuchs, Lennart Friis-Hansen, Daniel Goldenberger, Andrej Golle, Juha O Groonroos, Ines Hoffmann, Tomer Hoffmann, Harriet Hughes, Marina Ivanova, Peter Jezek, Gwennan Jones, Zeynep Ceren Karahan, Cornelia Lass-Flörl, Frédéric Laurent, Laura Leach, Matilde Lee Horsbøll Pedersen, Caroline Loiez, Maureen Lynch, Robert J Maloney, Martin Marsh, Olivia Milburn, Shanine Mitchell, Luke S P Moore, Lynn Moffat, Marianna Murdjeva, Michael E Murphy, Deepa Nayar, Giacomo Nigrisoli, Fionnuala O'Sullivan, Büşra Öz, Teresa Peach, Christina Petridou, Mojgan Prinz, Mitja Rak, Niamh Reidy, Gian Maria Rossolini, Anne-Laure Roux, Patricia Ruiz-Garbajosa, Kordo Saeed, Llanos Salar-Vidal, Carlos Salas Venero, Mathyruban Selvaratnam, Eric Senneville, Peter Starzengruber, Ben Talbot, Vanessa Taylor, Rihard Trebše, Deborah Wearmouth, Birgit Willinger, Marjan Wouthuyzen-Bakker, Brianne Couturier, Florence Allantaz

Faculty, Staff and Student Publications

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the …

The Brain Structure And Function Abnormalities Of Migraineurs: A Systematic Review And Neuroimaging Meta-Analysis, Wei Ruan, Tao Li, Jaewoong Lee, In Hyuk Bang, Wankun Deng, Xinxin Ma, Seung-Hee Yoo, Boyun Kim, Jiwen Li, Xiaoyi Yuan, Yu A An, Yin-Ying Wang, Yafen Liang, Matthew Deberge, Dongze Zhang, Zhen Zhou, Yanyu Wang, Josh Gorham, Jonathan G Seidman, Christine E Seidman, Sary F Aranki, Ragini Nair, Lei Li, Jagat Narula, Zhongming Zhao, Alemayehu G Abebe, Jochen Daniel Muehlschlegel, Kuang-Lei Tsai, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide

Causal Influence Of Linguistic Learning On Perceptual And Conceptual Processing: A Brain-Constrained Deep Neural Network Study Of Proper Names And Category Terms, Phuc T U Nguyen, Malte R Henningsen-Schomers, Friedemann Pulvermüller

Faculty, Staff and Student Publications

Language influences cognitive and conceptual processing, but the mechanisms through which such causal effects are realized in the human brain remain unknown. Here, we use a brain-constrained deep neural network model of category formation and symbol learning and analyze the emergent model's internal mechanisms at the neural circuit level. In one set of simulations, the network was presented with similar patterns of neural activity indexing instances of objects and actions belonging to the same categories. Biologically realistic Hebbian learning led to the formation of instance-specific neurons distributed across multiple areas of the network, and, in addition, to cell assembly circuits …

Energetic Trade-Offs In Migration Decision-Making, Reproductive Effort And Subsequent Parental Care In A Long-Distance Migratory Bird, Alexander R Schindler, Anthony D Fox, Christopher K Wikle, Bart M Ballard, Alyn J Walsh, Seán B A Kelly, Lei Cao, Larry R Griffin, Mitch D Weegman

Faculty, Staff and Student Publications

Migratory species trade-off long-distance movement with survival and reproduction, but the spatio-temporal scales at which these decisions occur are relatively unknown. Technological and statistical advances allow fine-scale study of animal decision-making, improving our understanding of possible causes and therefore conservation management. We quantified effects of reproductive preparation during spring migration on subsequent breeding outcomes, breeding outcomes on autumn migration characteristics and autumn migration characteristics on subsequent parental survival in Greenland white-fronted geese (

Iterative Patient Testing Of A Stimuli-Responsive Swallowing Activity Sensor To Promote Extended User Engagement During The First Year After Radiation: Multiphase Remote And In-Person Observational Cohort Study, Eileen H Shinn, Adam S Garden, Susan K Peterson, Dylan J Leupi, Minxing Chen, Rachel Blau, Laura Becerra, Tarek Rafeedi, Julian Ramirez, Daniel Rodriquez, Finley Vanfossen, Sydney Zehner, Patrick P Mercier, Joseph Wang, Kate Hutcheson, Ehab Hanna, Darren J Lipomi

Faculty, Staff and Student Publications

BACKGROUND: Frequent sensor-assisted monitoring of changes in swallowing function may help improve detection of radiation-associated dysphagia before it becomes permanent. While our group has prototyped an epidermal strain/surface electromyography sensor that can detect minute changes in swallowing muscle movement, it is unknown whether patients with head and neck cancer would be willing to wear such a device at home after radiation for several months.

OBJECTIVE: We iteratively assessed patients' design preferences and perceived barriers to long-term use of the prototype sensor.

METHODS: In study 1 (questionnaire only), survivors of pharyngeal cancer who were 3-5 years post treatment and part of …

Experience With A Hybrid Recruitment Approach Of Patient-Facing Web Portal Screening And Subsequent Phone And Medical Record Review For A Neurosurgical Intervention Trial For Chronic Ischemic Stroke Disability (Pisces Iii), Brad J Kolls, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, David S Albers, Daniel T Laskowitz

Faculty, Staff and Student Publications

BACKGROUND: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier …

Protein-Folding Chaperones Predict Structure-Function Relationships And Cancer Risk In Brca1 Mutation Carriers, Brant Gracia, Patricia Montes, Angelica Maria Gutierrez, Banu Arun, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Predicting the risk of cancer mutations is critical for early detection and prevention, but differences in allelic severity of human carriers confound risk predictions. Here, we elucidate protein folding as a cellular mechanism driving differences in mutation severity of tumor suppressor BRCA1. Using a high-throughput protein-protein interaction assay, we show that protein-folding chaperone binding patterns predict the pathogenicity of variants in the BRCA1 C-terminal (BRCT) domain. HSP70 selectively binds 94% of pathogenic BRCA1-BRCT variants, most of which engage HSP70 more than HSP90. Remarkably, the magnitude of HSP70 binding linearly correlates with loss of folding and function. We identify a prevalent …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Prognostic Risk Signature In Patients With Acute Myeloid Leukemia Treated With Hypomethylating Agents And Venetoclax, Alex Bataller, Alexandre Bazinet, Courtney D Dinardo, Abhishek Maiti, Gautam Borthakur, Naval G Daver, Nicholas J Short, Elias J Jabbour, Ghayas C Issa, Naveen Pemmaraju, Musa Yilmaz, Guillermo Montalban-Bravo, Koichi Takahashi, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Hypomethylating agents (HMAs) and venetoclax (Ven) represent the standard of care for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. However, the European LeukemiaNet (ELN) risk classifications have been validated for patients treated with intensive therapy. In this study, we validate a recently proposed new molecular prognostic risk signature (mPRS) for patients with AML treated with HMAs and Ven. This classification allocated patients to favorable, intermediate (N/KRAS or FLT3-internal tandem duplication mutations), and lower (TP53 mutations) benefit groups. We retrospectively analyzed 159 patients treated with HMA and Ven. The mPRS classification allocated 74 (47%), 31 (19%), …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …

Bridging Therapy With Axicabtagene Ciloleucel For Large B-Cell Lymphoma: Results From The Us Lymphoma Car-T Consortium, Michael D Jain, Miriam T Jacobs, Feng Gao, Loretta J Nastoupil, Jay Y Spiegel, Yi Lin, Saurabh Dahiya, Matthew Lunning, Lazaros Lekakis, Patrick Reagan, Olalekan Oluwole, Joseph Mcguirk, Abhinav Deol, Alison R Sehgal, Andre Goy, Brian T Hill, Charalambos Andreadis, Javier Munoz, Julio C Chavez, N Nora Bennani, Aaron P Rapoport, Julie M Vose, David Miklos, Sattva S Neelapu, Frederick L Locke, Armin Ghobadi

Faculty, Staff and Student Publications

During the manufacturing period of autologous chimeric antigen receptor (CAR) T-cell therapy, patients may experience a decline in their condition due to cancer progression. In this study, we investigated the impact of bridging therapy (BT) on the outcome of patients with relapsed/refractory large B-cell lymphoma who received antilymphoma treatment between leukapheresis and axicabtagene ciloleucel (axi-cel) infusion. We conducted our analysis using data from the multicenter US Lymphoma CAR-T Consortium, with a median follow-up of 33 months (range, 4.3-42.1). Out of the 298 patients who underwent leukapheresis, 275 patients received axi-cel. A total 52% of patients (n = 143) who received …

Differential Upregulation Of Th1/Th17-Associated Proteins And Pd-L1 In Granulomatous Mycosis Fungoides, Mario L Marques-Piubelli, Jesus Navarrete, Debora A Ledesma, Courtney W Hudgens, Rossana N Lazcano, Ali Alani, Auris Huen, Madeleine Duvic, Priyadharsini Nagarajan, Phyu P Aung, Ignacio I Wistuba, Jonathan L Curry, Roberto N Miranda, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients …

A Phase 1/2 Study Of Mini-Hyper-Cvd Plus Venetoclax In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Nitin Jain, Jayastu Senapati, Lewis Nasr, Fadi G Haddad, Zhenhua Li, Yu-Chih Hsiao, Jun J Yang, Naveen Pemmaraju, Maro Ohanian, William G Wierda, Guillermo Montalban-Bravo, Gautam Borthakur, Lina Han, Lianchun Xiao, Xuelin Huang, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of …

Mortality After Major Cardiovascular Events In Survivors Of Childhood Cancer, Wendy Bottinor, Cindy Im, David R Doody, Saro H Armenian, Alexander Arynchyn, Borah Hong, Rebecca M Howell, David R Jacobs, Kirsten K Ness, Kevin C Oeffinger, Alexander P Reiner, Gregory T Armstrong, Yutaka Yasui, Eric J Chow

Faculty, Staff and Student Publications

Background: Adult survivors of childhood cancer are at risk for cardiovascular events.

Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.

Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical …

Grit And Second Language Learning Engagement: The Mediating Role Of Affect Balance, Chenggang Wu, Xiaoyong Tian, Hui Jin

Faculty, Staff and Student Publications

The study of the relationship between key psychological attributes of learners and their engagement in second language (L2) learning helps to understand the critical personality mechanisms influencing language learning. The present study examined the L2 learning engagement from the perspectives of grit (i.e., consistent efforts and interests devoted to a long-term goal) and affect balance (a notion that takes into account both positive and negative emotions concurrently, assessing and evaluating which side holds more significance or influence). A cohort of English L2 learners (

Fully Automated Deep Learning Based Auto-Contouring Of Liver Segments And Spleen On Contrast-Enhanced Ct Images, Aashish C Gupta, Guillaume Cazoulat, Mais Al Taie, Sireesha Yedururi, Bastien Rigaud, Austin Castelo, John Wood, Cenji Yu, Caleb O'Connor, Usama Salem, Jessica Albuquerque Marques Silva, Aaron Kyle Jones, Molly Mcculloch, Bruno C Odisio, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Manual delineation of liver segments on computed tomography (CT) images for primary/secondary liver cancer (LC) patients is time-intensive and prone to inter/intra-observer variability. Therefore, we developed a deep-learning-based model to auto-contour liver segments and spleen on contrast-enhanced CT (CECT) images. We trained two models using 3d patch-based attention U-Net ([Formula: see text] and 3d full resolution of nnU-Net ([Formula: see text] to determine the best architecture ([Formula: see text]. BA was used with vessels ([Formula: see text] and spleen ([Formula: see text] to assess the impact on segment contouring. Models were trained, validated, and tested on 160 ([Formula: see text]), …

Clinical Benefit From Docetaxel +/- Ramucirumab Is Not Associated With Mutation Status In Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed On Platinum Doublets And Immunotherapy, Kang Qin, Kaiwen Wang, Shenduo Li, Lingzhi Hong, Priyadharshini Padmakumar, Rinsurongkawong Waree, Shawna M Hubert, Xiuning Le, Natalie Vokes, Kunal Rai, Ara Vaporciyan, Don L Gibbons, John V Heymach, J Jack Lee, Scott E Woodman, Caroline Chung, David A Jaffray, Mehmet Altan, Yanyan Lou, Jianjun Zhang

Faculty, Staff and Student Publications

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel …

Characteristics Of Early Pancreatic Cancer: Comparison Between Stage 1a And Stage 1b Pancreatic Cancer In Multicenter Clinical Data Warehouse Study, Hyo Suk Kim, Young Hoon Choi, Jae Sin Lee, Ik Hyun Jo, Sung Woo Ko, Kyu Hyun Paik, Hyun Ho Choi, Han Hee Lee, Yeon Soo Lim, Chang Nyol Paik, In Seok Lee, Jae Hyuck Chang

Faculty, Staff and Student Publications

BACKGROUND: Little is known about the characteristics of early pancreatic cancer. We aimed to identify the characteristics, clues for early detection, and prognostic factors for early pancreatic cancer by analyzing a large number of patients with stage 1 pancreatic cancer.

METHODS: A clinical data warehouse that includes databases of all the medical records of eight academic institutions was used to select and analyze patients with pancreatic cancer that had been diagnosed from January 2010 to May 2023.

RESULTS: In total, 257 stage 1 pancreatic cancer patients were included. There were 134 men (52%), and the average age was 67.2 ± …

Comparing Anesthesia And Surgery Controlled Time For Primary Total Knee And Hip Arthroplasty Between An Academic Medical Center And A Community Hospital: Retrospective Cohort Study, Thy B Nguyen, Nathaen Weitzel, Craig Hogan, Rachel M Kacmar, Kayla M Williamson, Jack Pattee, Vesna Jevtovic-Todorovic, Colby G Simmons, Adeel Ahmad Faruki

Faculty, Staff and Student Publications

BACKGROUND: Osteoarthritis is a significant cause of disability, resulting in increased joint replacement surgeries and health care costs. Establishing benchmarks that more accurately predict surgical duration could help to decrease costs, maximize efficiency, and improve patient experience. We compared the anesthesia-controlled time (ACT) and surgery-controlled time (SCT) of primary total knee (TKA) and total hip arthroplasties (THA) between an academic medical center (AMC) and a community hospital (CH) for 2 orthopedic surgeons.

OBJECTIVE: This study aims to validate and compare benchmarking times for ACT and SCT in a single patient population at both an AMC and a CH.

METHODS: This …

The Future Of Targeted Therapy For Leiomyosarcoma, Ryan A Denu, Amanda M Dann, Emily Z Keung, Michael S Nakazawa, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the …

Endoscopic Hyperspectral Imaging System To Discriminate Tissue Characteristics In Tissue Phantom And Orthotopic Mouse Pancreatic Tumor Model, Na Eun Mun, Thi Kim Chi Tran, Dong Hui Park, Jin Hee Im, Jae Il Park, Thanh Dat Le, Young Jin Moon, Seong-Young Kwon, Su Woong Yoo

Faculty, Staff and Student Publications

In this study, we developed an endoscopic hyperspectral imaging (eHSI) system and evaluated its performance in analyzing tissues within tissue phantoms and orthotopic mouse pancreatic tumor models. Our custom-built eHSI system incorporated a liquid crystal tunable filter. To assess its tissue discrimination capabilities, we acquired images of tissue phantoms, distinguishing between fat and muscle regions. The system underwent supervised training using labeled samples, and this classification model was then applied to other tissue phantom images for evaluation. In the tissue phantom experiment, the eHSI effectively differentiated muscle from fat and background tissues. The precision scores regarding fat tissue classification were …

Cagi, The Critical Assessment Of Genome Interpretation, Establishes Progress And Prospects For Computational Genetic Variant Interpretation Methods, Critical Assessment Of Genome Interpretation Consortium

Faculty, Staff and Student Publications

BACKGROUND: The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.

RESULTS: Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was …

Estrogen Receptor Mutations As Novel Targets For Immunotherapy In Metastatic Estrogen Receptor-Positive Breast Cancer, Jonathan Goldberg, Na Qiao, Jennifer L Guerriero, Brett Gross, Yagiz Meneksedag, Yoshimi F Lu, Anne V Philips, Tasnim Rahman, Funda Meric-Bernstam, Jason Roszik, Ken Chen, Rinath Jeselsohn, Sara M Tolaney, George E Peoples, Gheath Alatrash, Elizabeth A Mittendorf

Faculty, Staff and Student Publications

UNLABELLED: Estrogen receptor-positive (ER+) breast cancer is not considered immunogenic and, to date, has been proven resistant to immunotherapy. Endocrine therapy remains the cornerstone of treatment for ER+ breast cancers. However, constitutively activating mutations in the estrogen receptor alpha (ESR1) gene can emerge during treatment, rendering tumors resistant to endocrine therapy. Although these mutations represent a pathway of resistance, they also represent a potential source of neoepitopes that can be targeted by immunotherapy. In this study, we investigated ESR1 mutations as novel targets for breast cancer immunotherapy. Using machine learning algorithms, we identified ESR1-derived peptides predicted to form stable complexes …

Somatostatin Receptor Subtype-2 Targeting System For Specific Delivery Of Temozolomide, Solmaz Aghaamiri, Sukhen C Ghosh, Servando Hernandez Vargas, Daniel M Halperin, Ali Azhdarinia

Faculty, Staff and Student Publications

Temozolomide (TMZ) is a DNA alkylating agent that produces objective responses in patients with neuroendocrine tumors (NETs) when the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is inactivated. At high doses, TMZ therapy exhausts MGMT activity but also produces dose-limiting toxicities. To reduce off-target effects, we converted the clinically approved radiotracer 68Ga-DOTA-TOC into a peptide-drug conjugate (PDC) for targeted delivery of TMZ to somatostatin receptor subtype-2 (SSTR2)-positive tumor cells. We used an integrated radiolabeling strategy for direct quantitative assessment of receptor binding, pharmacokinetics, and tissue biodistribution. In vitro studies revealed selective binding to SSTR2-positive cells with high affinity (5.98 ± 0.96 …

Comparative Genomics Incorporating Translocation Renal Cell Carcinoma Mouse Model Reveals Molecular Mechanisms Of Tumorigenesis, Gopinath Prakasam, Akhilesh Mishra, Alana Christie, Jeffrey Miyata, Deyssy Carrillo, Vanina T Tcheuyap, Hui Ye, Quyen N Do, Yunguan Wang, Oscar Reig Torras, Ramesh Butti, Hua Zhong, Jeffrey Gagan, Kevin B Jones, Thomas J Carroll, Zora Modrusan, Steffen Durinck, Mai-Carmen Requena-Komuro, Noelle S Williams, Ivan Pedrosa, Tao Wang, Dinesh Rakheja, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition. Electron microscopy of tRCC tumors showed lysosome expansion, and functional studies revealed simultaneous …

Use Of Crispr Interference For Efficient And Rapid Gene Inactivation In Fusobacterium Nucleatum, Peng Zhou, Bibek G C, Flynn Stolte, Chenggang Wu

Faculty, Staff and Student Publications

Gene inactivation by creating in-frame deletion mutations in Fusobacterium nucleatum is time consuming, and most fusobacterial strains are genetically intractable. Addressing these problems, we introduced a riboswitch-based inducible CRISPR interference (CRISPRi) system. This system employs the nuclease-inactive Streptococcus pyogenes Cas9 protein (dCas9), specifically guided to the gene of interest by a constantly expressed single-guide RNA (sgRNA). Mechanistically, this dCas9-sgRNA complex serves as an insurmountable roadblock for RNA polymerase, thus repressing the target gene transcription. Leveraging this system, we first examined two non-essential genes, ftsX and radD, which are pivotal for fusobacterial cytokinesis and coaggregation. Upon adding the inducer, theophylline, …

Orbital And Periocular Complications In Patients With Sinonasal Tumours With Orbital Invasion, Jiawei Zhao, Xinyang Jiang, Ehab Hanna, Shirley Y Su, Amy Moreno, Brandon Gunn, Steven Jay Frank, Renata Ferrarotto, Jing Ning, Bita Esmaeli

Faculty, Staff and Student Publications

Aims: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments.

Methods: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not.

Results: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The …

Data Encoding For Healthcare Data Democratization And Information Leakage Prevention, Anshul Thakur, Tingting Zhu, Vinayak Abrol, Jacob Armstrong, Yujiang Wang, David A Clifton

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The lack of data democratization and information leakage from trained models hinder the development and acceptance of robust deep learning-based healthcare solutions. This paper argues that irreversible data encoding can provide an effective solution to achieve data democratization without violating the privacy constraints imposed on healthcare data and clinical models. An ideal encoding framework transforms the data into a new space where it is imperceptible to a manual or computational inspection. However, encoded data should preserve the semantics of the original data such that deep learning models can be trained effectively. This paper hypothesizes the characteristics of the desired encoding …

Collagen Type Xii Is Undetectable In Keratoconus Bowman’S Layer, Mohammed Rigi, Hyeck-Soo Son, Loren Moon, Mario Matthaei, Divya Srikumaran, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Faculty, Staff and Student Publications

PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (

METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,

RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared to controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane, and stroma.

CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that

Impact Of Immunopathy And Coagulopathy On Multi-Organ Failure And Mortality In A Lethal Porcine Model Of Controlled And Uncontrolled Hemorrhage, Milomir O Simovic, James Bynum, Bin Liu, Jurandir J Dalle Lucca, Yansong Li

Faculty, Staff and Student Publications

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic …