Medicine and Health Sciences Commons^™

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Exome Sequencing Identifies Helb As A Novel Susceptibility Gene For Non-Mucinous, Non-High-Grade-Serous Epithelial Ovarian Cancer, Ed M Dicks, Jonthan P Tyrer, Suzana Ezquina, Michelle Jones, John Baierl, Pei-Chen Peng, Michael Diaz, Ellen Goode, Stacey J Winham, Thilo Dörk, Toon Van Gorp, Anna De Fazio, David D L Bowtell, Dale W Garsed, Kunle Odunsi, Kirsten Moysich, Marina Pavanello, Florentia Fostira, Penelope M Webb, Jana Soukupová, Paul A Cohen, Weiva Sieh, Renée Turzanski Fortner, Charite Ricker, Beth Karlan, Ian Campbell, James D Brenton, Susan J Ramus, Simon A Gayther, Paul D P Pharoah

Faculty, Staff and Student Publications

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which …

Immunelens Characterizes Systemic Immune Dysregulation In Aging And Cancer, Robert Bentham, Thomas P Jones, James R M Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas B K Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, Genomics England Consortium, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower …

Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong

Faculty, Staff and Student Publications

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Methods: Human serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1KO) mice were fed a 45% high-fat diet, with serum samples collected every 2 weeks to monitor LRG1 and insulin levels throughout diet-induced obesity. MIN6 beta cells were used to investigate the effects …

Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography, Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Significance: Systemic sclerosis (SSc) is a chronic idiopathic disease that causes immune dysregulation, vasculopathy, and organ fibrosis that affects more than 3 million people in the US alone. The modified Rodnan skin score (mRSS) is the current gold standard for diagnosing and staging skin fibrosis in SSc. However, mRSS is subjective, requires extensive training, and has high observer variability.

Aim: We aim to provide a quantitative method for the assessment of fibrosis.

Approach: We utilized optical coherence tomography (OCT), its extensions, optical coherence elastography (OCE), and OCT angiography (OCTA) to evaluate SSc-like fibrosis and therapy response in a mouse model. …

Relapsed Acute Myeloid Leukemia With Early Presentation As Leukemia Cutis, Refractory To Second-Line Treatment, Emin Gayibov, Aditi Karambelkar, Virushnee Senthilkumar, Amita J Dsouza, Amit K Correa

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a hematologic malignancy with a poor prognosis, often presenting with systemic and extramedullary manifestations. Leukemia cutis (LC), the infiltration of leukemic cells into the skin, is a rare and clinically significant complication of AML. It often signals extramedullary disease involvement, may precede systemic relapse, and is associated with poor survival outcomes. We report the case of a 36-year-old female with AML who developed recurrent, reddish-brown nodular skin lesions on the face, trunk, and extremities, consistent with LC. Despite achieving initial remission with induction and consolidation chemotherapy, she experienced early LC recurrence, pancytopenia, hepatobiliary dysfunction, and …

Liver Involvement In A Large Cohort Of Patients With Erythropoietic Protoporphyria Or X-Linked Protoporphyria, Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine Mcdonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan Mcguire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani, Porphyrias Consortium Of The Rare Diseases Clinical Research Network

Faculty, Staff and Student Publications

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at …

Epidemiology Of Myositis, Fnu Duremala, Eleni Tiniakou, James Andrews

Faculty, Staff and Student Publications

Purpose of review: This review aims to synthesize recent developments in the epidemiology of idiopathic inflammatory myopathies (IIMs), focusing on incidence, prevalence, disease classification, and clinical outcomes.

Recent findings: IIM is a rare group of autoimmune diseases characterized by muscle weakness and systemic involvement, with incidence rates ranging from 0.2 to 2 cases per 100 000 person-years. The role of myositis-specific autoantibodies (MSAs) in stratifying disease risk and prognosis is increasingly recognized, such as in anti-MDA5 positive DM, which is associated with a high risk of rapidly progressive interstitial lung disease. Furthermore, patients with IIM exhibit elevated risks of comorbidities, …

Patients Residing In Rural Areas Transferred For Mechanical Thrombectomy Undergo Decreased Catheter-Based Treatment, Amanda L Jagolino-Cole, Deepa Dongarwar, Sushanth Aroor, Sunil A Sheth, Anjail Sharrief, Kori S Zachrison, Dileep Yavagal, Kaiz S Asif

Faculty, Staff and Student Publications

Background: Nearly one fifth of the US population resides in rural areas. Although endovascular therapy can substantially improve clinical outcomes in patients treated with large vessel occlusion acute ischemic stroke, the penetration and outcomes of this therapy in rural US populations remain incompletely characterized.

Methods: From the nationwide Get With The Guidelines Stroke registry, incorporating select social determinants of health (SDOH) by the Institute for Health Metrics and Evaluation registry (2016-2019), we identified patients with acute ischemic stroke and transient ischemic attack who were transferred from their presenting hospitals to other hospitals with the intention of thrombectomy evaluation, for patients …

Endovascular Therapy In Patients With Acute Ischemic Stroke With Large Infarct: A Guideline From The Society Of Vascular And Interventional Neurology, Maxim Mokin, Tudor G Jovin, Sunil A Sheth, Thanh N Nguyen, Kaiz S Asif, Ameer E Hassan, Ashutosh P Jadhav, Cynthia Kenmuir, David S Liebeskind, Ossama Mansour, Raul G Nogueira, Robin Novakovic, Santiago Ortega-Gutierrez, Albert J Yoo, Waldo R Guerrero, Amer M Malik

Faculty, Staff and Student Publications

Background: Recent randomized clinical trials of endovascular therapy in patients with large infarct provided new evidence in support of endovascular interventions in patients with acute ischemic stroke. The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee aims to provide up-to-date recommendations on focused relevant clinical questions. Here, we review current evidence and provide recommendations for the selection and endovascular treatment of patients with anterior circulation large vessel occlusion and large infarct.

Methods: The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the …

Histology-Grounded Automated Plaque Subtype Segmentation In Intravascular Optical Coherence Tomography, Paul Young, Drew Nolen, Thomas E Milner, Alexandra Gruslova, Deborah Vela, Louis Maximilian Buja, Luis A Diaz Sanmartin, Paul Rad, Marc D Feldman

Faculty, Staff and Student Publications

Background: Intravascular optical coherence tomography (IVOCT) adoption has been limited by the complexity of image interpretation. The interpretation of histologic subtypes beyond lipid, calcium, and fibrous is challenging to human readers. To assist and standardize IVOCT image analysis, we demonstrate an artificial intelligence algorithm based on a histology data set that identifies lipid pools, fibrofatty, calcified lipid, and calcified fibrous in human coronary arteries for the first time.

Methods: Sixty-seven human coronary arteries were imaged with IVOCT within 24 hours after death and then underwent histologic examination. IVOCT images were coregistered and segmented into histologic subtypes: lipid pools, fibrofatty tissue, …

Author Correction: Ctla4 Blockade Abrogates Keap1/Stk11-Related Resistance To Pd-(L)1 Inhibitors, Ferdinandos Skoulidis, Haniel A Araujo, Minh Truong Do, Yu Qian, Xin Sun, Ana Galan Cobo, John T Le, Meagan Montesion, Rachael Palmer, Nadine Jahchan, Joseph M Juan, Chengyin Min, Yi Yu, Xuewen Pan, Kathryn C Arbour, Natalie Vokes, Stephanie T Schmidt, David Molkentine, Dwight H Owen, Regan Memmott, Pradnya D Patil, Melina E Marmarelis, Mark M Awad, Joseph C Murray, Jessica A Hellyer, Justin F Gainor, Anastasios Dimou, Christine M Bestvina, Catherine A Shu, Jonathan W Riess, Collin M Blakely, Chad V Pecot, Laura Mezquita, Fabrizio Tabbó, Matthias Scheffler, Subba Digumarthy, Meghan J Mooradian, Adrian G Sacher, Sally C M Lau, Andreas N Saltos, Julia Rotow, Rocio Perez Johnson, Corinne Liu, Tyler Stewart, Sarah B Goldberg, Jonathan Killam, Zenta Walther, Kurt Schalper, Kurtis D Davies, Mark G Woodcock, Valsamo Anagnostou, Kristen A Marrone, Patrick M Forde, Biagio Ricciuti, Deepti Venkatraman, Eliezer M Van Allen, Amy L Cummings, Jonathan W Goldman, Hiram Shaish, Melanie Kier, Sharyn Katz, Charu Aggarwal, Ying Ni, Joseph T Azok, Jeremy Segal, Lauren Ritterhouse, Joel W Neal, Ludovic Lacroix, Yasir Y Elamin, Marcelo V Negrao, Xiuning Le, Vincent K Lam, Whitney E Lewis, Haley N Kemp, Brett Carter, Jack A Roth, Stephen Swisher, Richard Lee, Teng Zhou, Alissa Poteete, Yifan Kong, Tomohiro Takehara, Alvaro Guimaraes Paula, Edwin R Parra Cuentas, Carmen Behrens, Ignacio I Wistuba, Jianjun Zhang, George R Blumenschein, Carl Gay, Lauren A Byers, Don L Gibbons, Anne Tsao, J Jack Lee, Trever G Bivona, D Ross Camidge, Jhannelle E Gray, Natasha B Leighl, Benjamin Levy, Julie R Brahmer, Marina C Garassino, David R Gandara, Edward B Garon, Naiyer A Rizvi, Giorgio Vittorio Scagliotti, Jürgen Wolf, David Planchard, Benjamin Besse, Roy S Herbst, Heather A Wakelee, Nathan A Pennell, Alice T Shaw, Pasi A Jänne, David P Carbone, Matthew D Hellmann, Charles M Rudin, Lee Albacker, Helen Mann, Zhou Zhu, Zhongwu Lai, Ross Stewart, Solange Peters, Melissa L Johnson, Kwok K Wong, Alan Huang, Monte M Winslow, Michael J Rosen, Ian P Winters, Vassiliki A Papadimitrakopoulou, Tina Cascone, Philip Jewsbury, John V Heymach

Faculty, Staff and Student Publications

No abstract provided.

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …

Guidelines For Minimal Reporting Requirements, Design And Interpretation Of Experiments Involving The Use Of Eukaryotic Dual Gene Expression Reporters (Mindr), Gary Loughran, Dmitry E Andreev, Ilya M Terenin, Olivier Namy, Martin Mikl, Martina M Yordanova, C Joel Mcmanus, Andrew E Firth, John F Atkins, Christopher S Fraser, Zoya Ignatova, Shintaro Iwasaki, Joanna Kufel, Ola Larsson, Sebastian A Leidel, Alexander S Mankin, Marco Mariotti, Marvin E Tanenbaum, Ivan Topisirovic, Nora Vázquez-Laslop, Gabriela Viero, Neva Caliskan, Yiwen Chen, Patricia L Clark, Jonathan D Dinman, Philip J Farabaugh, Wendy V Gilbert, Pavel Ivanov, Jeffrey S Kieft, Oliver Mühlemann, Matthew S Sachs, Ivan N Shatsky, Nahum Sonenberg, Anna-Lena Steckelberg, Anne E Willis, Michael T Woodside, Leos Shivaya Valasek, Sergey E Dmitriev, Pavel V Baranov

Faculty, Staff and Student Publications

Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. …

Monte Carlo Modeling Of An Experimental Benchtop L-Shell X-Ray Fluorescence Imaging/Ct System Adopting Two Silicone Drift Detectors, Neerajan Nepal, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

L-shell x-ray fluorescence (XRF) photons induced from gold nanoparticles (GNPs) after being irradiated by an x-ray beam allow for highly sensitive XRF imaging/computed tomography (XFCT) of biological samples containing GNPs at low concentrations on the order of parts-per-million (ppm). The primary goal of this Monte Carlo (MC) study was to investigate the feasibility of upgrading an existing experimental benchtop XRF/XFCT imaging setup adopting a single silicon drift detector (SDD), developed based on the aforementioned concept (often known as L-shell XFCT), by deploying another SDD within the same setup. Specifically, an MC model of the original single SDD L-shell XFCT setup, …

Proceedings Of The National Cancer Institute Workshop On Combining Immunotherapy With Radiotherapy: Challenges And Opportunities For Clinical Translation, Zachary S Morris, Sandra Demaria, Arta M Monjazeb, Silvia C Formenti, Ralph R Weichselbaum, James Welsh, Heiko Enderling, Jonathan D Schoenfeld, Joshua D Brody, Heather M Mcgee, Michele Mondini, Michael S Kent, Kristina H Young, Lorenzo Galluzzi, Sana D Karam, Willemijn S M E Theelen, Joe Y Chang, Mai Anh Huynh, Adi Daib, Sean Pitroda, Caroline Chung, Raphael Serre, Clemens Grassberger, Jie Deng, Quaovi H Sodji, Anthony T Nguyen, Ravi B Patel, Simone Krebs, Anusha Kalbasi, Caroline Kerr, Claire Vanpouille-Box, Logan Vick, Todd A Aguilera, Irene M Ong, Fernanda Herrera, Hari Menon, Deedee Smart, Jalal Ahmed, Robyn D Gartrell, Christina L Roland, Fatemeh Fekrmandi, Binita Chakraborty, Eric H Bent, Tracy J Berg, Alan Hutson, Samir Khleif, Andrew G Sikora, Lawrence Fong

Faculty, Staff and Student Publications

Radiotherapy both promotes and antagonises tumour immune recognition. Some clinical studies show improved patient outcomes when immunotherapies are integrated with radiotherapy. Safe, greater than additive, clinical response to the combination is limited to a subset of patients, however, and how radiotherapy can best be combined with immunotherapies remains unclear. The National Cancer Institute-Immuno-Oncology Translational Network-Society for Immunotherapy of Cancer-American Association of Immunology Workshop on Combining Immunotherapy with Radiotherapy was convened to identify and prioritise opportunities and challenges for radiotherapy and immunotherapy combinations. Sessions examined the immune effects of radiation, barriers to anti-tumour immune response, previous clinical trial data, immunological and …

Nulliparous With Class Iii Obesity At Term: Labor Induction Or Cesarean Delivery Without Labor, Yossi Bart, Rachel L Wiley, Ipsita Ghose, Michal Fishel Bartal, Khalil M Chahine, Suneet P Chauhan, Sean Blackwell, Baha M Sibai

Faculty, Staff and Student Publications

Objective: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2).

Study design: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a …

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …

Erratum: Comparison Of The Neer Classification To The 2018 Update Of The Orthopedic Trauma Association/Ao Fracture Classification For Classifying Proximal Humerus Fractures: Erratum, Meir T Marmor, Julie Agel, Jarrod Dumpe, James F Kellam, Geoffrey S Marecek, Eric Meinberg, Mai P Nguyen, Stephen Sims, Gillian L Soles, Matthew D Karam

Faculty, Staff and Student Publications

This corrects the article "Comparison of the Neer classification to the 2018 update of the Orthopedic Trauma Association/AO fracture classification for classifying proximal humerus fractures" in volume 5, e200.

Synchronous Presentation Of Right Parotid Branchial Cleft Cyst And Left Neck Hpv-Associated Cystic Metastatic Squamous Cell Carcinoma: A Diagnostic Quandary, Syed H A Naqvi, Syed H S Naqvi, David Allen, Arturo A Eguia, Jing Liu, Ron J Karni

Faculty, Staff and Student Publications

Branchial cleft cyst arising within the parotid space is considered an extremely rare phenomenon. In contrast, cystic squamous cell carcinoma in the lateral neck is not an uncommon presentation of HPV-related head and neck cancer. Although they have singly been narrated in literature, simultaneous expression of these anomalies has yet to be reported. We describe a case of synchronous presentation of branchial cleft cyst of the right parotid gland and cystic metastatic squamous cell carcinoma of the left neck. These findings are discussed in light of the challenges in fine needle aspiration biopsy of cystic masses, and the risk of …

Infected Ruptured Parathyroid Cyst Presenting With Hypercalcemia And Airway Obstruction: A Case Report, Syed H A Naqvi, Paul Hung, David Allen, Syed H S Naqvi, Elizabeth T Ricks, Karan Saluja, Arturo A Eguia, Ron J Karni

Faculty, Staff and Student Publications

Parathyroid cysts (PC) are infrequently encountered and characterize less than 1% of all head and neck masses. When present, PCs may present as a palpable neck mass and lead to hypercalcemia and rarely respiratory depression. Furthermore, the diagnostics of PCs is difficult as they can masquerade as a thyroid or mediastinal mass given their proximity. PCs are theorized to be a progression of parathyroid adenomas and often routine surgical excision is sufficient for cure. To our knowledge, there is no documented report of a patient with an infected parathyroid cyst that led to severe dyspnea. This case describes our experience …

Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application To Injured Brain, Karthik Mouli, Anton V Liopo, Emily A Mchugh, Erica Underwood, Jing Zhao, Pramod K Dash, Anh T T Vo, Vikas H Malojirao, Muralidhar L Hegde, James M Tour, Paul J Derry, Thomas A Kent

Faculty, Staff and Student Publications

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a …

Temperature-Controlled Radiofrequency Treatment Of The Nasal Valve In Nasal Airway Obstruction Patients With Septal Deviation, Dennis M Tang, Philip G Chen, Arthur W Wu, William C Yao

Faculty, Staff and Student Publications

Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.

Outcomes Of Standard-Risk Multiple Myeloma Patients Who Undergo Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Zhongya Wang, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Naureen Syed, Yosra Aljawai, Hans C Lee, Krina K Patel, Melody R Becnel, Christine Ye, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. We sought to evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. This was a single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification. A total of 1000 SRMM …

In Pursuit Of Ki-Rads: Toward A Single, Evidence-Based Imaging Classification Of Renal Masses, Stuart G Silverman, Ivan Pedrosa, Nicola Schieda, Vitaly Margulis, Payal Kapur, Matthew S Davenport

Faculty, Staff and Student Publications

Despite the successful application of Imaging Reporting and Data Systems to improve the radiologic description and management of disease in many organs, one does not yet exist for the kidney. Instead, the radiologic approach to the kidney has focused on the Bosniak classification system, which is based on imaging characteristics for cystic renal masses, and detecting macroscopic fat within solid renal masses. Radiologically, cystic and solid renal masses are categorized and evaluated separately because of historical precedent, differences in appearance at imaging, and differences in biologic behavior. However, the World Health Organization classification of renal neoplasms does not support such …

Proteasome Augmentation Mitigates Age-Related Cognitive Decline In Mice, Danitra Parker, Kanisa Davidson, Pawel A Osmulski, Maria Gaczynska, Andrew M Pickering

Faculty, Staff and Student Publications

The aging brain experiences a significant decline in proteasome function. The proteasome is critical for many key neuronal functions including neuronal plasticity, and memory formation/retention. Treatment with proteasome inhibitors impairs these processes. Our study reveals a marked reduction in 20S and 26S proteasome activities in aged mice brains, including in the hippocampus, this is driven by reduced functionality of aged proteasome. The decline in proteasome activity is matched by a decline in 20S proteasome assembly. In contrast, 26S proteasome assembly was found to increase with age, though 26S proteasome activity was still found to decline. Our data suggests that age-related …

Open-Hybrid Aortic Stent Placement For Recurrent Coarctation In Complex Single Ventricles, Andrew K Morse, Blaz Podgorsek, Julija Dobrila, Zachary A Cerra, Kiran K Mallula, Muhammad S Khan, Christopher E Greenleaf, Jorge D Salazar, Damien J Lapar, Peter C Chen

Faculty, Staff and Student Publications

Recurrent coarctation of the aorta in patients with hypoplastic left heart syndrome requires timely intervention to limit ventricular dysfunction and atrioventricular valve regurgitation. Current strategies include catheter-based intervention in adequately sized patients or surgical arch augmentation at the time of a concomitant operation. We report an open-hybrid surgical technique with placement of a balloon-expandable stent that can later be expanded to an adult size as the patient grows. Limiting the arch dissection reduces the risk to the left recurrent laryngeal nerve and shortens anterograde cerebral perfusion time.

Medical Image Segmentation Assisted With Clinical Inputs Via Language Encoder In A Deep Learning Framework, Hengrui Zhao, Biling Wang, Deepkumar Mistry, Jing Wang, Michael Dohopolski, Daniel Yang, Weiguo Lu, Steve Jiang, Dan Nguyen

Faculty, Staff and Student Publications

Introduction: Auto-segmentation of tumor volumes and organs at risk (OARs) is a critical step in cancer radiotherapy treatment planning, where rapid, precise adjustments to treatment plans are required to match the patient anatomy. Although auto-segmentation has been clinically accepted for most OARs, auto-segmentation of tumor volumes, particularly clinical target volumes (CTVs), remains a challenge. This difficulty arises because images alone are often insufficient to capture the necessary information for accurate delineation of microscopic tumor invasion invisible on the image itself.

Methods: We propose a deep learning-based medical image segmentation framework designed to mimic the clinical process of delineating CTVs and …

The Associations Of Sensory Impairment With 10-Year Risk Of Dementia And Alzheimer's Disease: The Health And Retirement Study, 2010-2020, Kun Li, Rahul Ghosal, Donglan Zhang, Yike Li, Matthew C Lohman, Monique J Brown, Anwar T Merchant, Chih-Hsiang Yang, Jean Neils-Strunjas, Daniela B Friedman, Jingkai Wei

Faculty, Staff and Student Publications

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. …

Depletion Of Acetyl-Coa Carboxylase 1 Facilitates Epithelial-Mesenchymal Transition In Prostate Cancer Cells By Activating The Mapk/Erk Pathway, Jiarun Lai, Shaoyou Liu, Yupeng Chen, Jian Chen, Jinchuang Li, Zhenguo Liang, Xinyue Mei, Yuanfa Feng, Zhaodong Han, Funeng Jiang, Shengbang Yang, Yongding Wu, Huijing Tan, Junchen Liu, Huichan He, Weide Zhong

Faculty, Staff and Student Publications

Hyperactivation of fatty acid biosynthesis holds promise as a targeted therapeutic strategy in prostate cancer (PCa). However, inhibiting these enzymes could potentially promote metastatic progression in various other cancers. Herein, we found that depletion of acetyl-CoA carboxylase 1 (encoded by ACACA), the enzyme responsible for the first and rate-limiting step of de novo fatty acid biosynthesis, facilitated epithelial-mesenchymal transition (EMT) and migration of PCa cells. This finding was validated in vitro through cell migration assays and in vivo using a metastatic model established by tail vein injection of ACACA-depleted cells into BALB/c nude mice. Additionally, depletion of ACACA activated the …