Medicine and Health Sciences Commons^™

The Orf7a Protein Of Sars-Cov-2 Initiates Autophagy And Limits Autophagosome-Lysosome Fusion Via Degradation Of Snap29 To Promote Virus Replication, Peili Hou, Xuefeng Wang, Hongmei Wang, Tiecheng Wang, Zhangping Yu, Chunqing Xu, Yudong Zhao, Wenqi Wang, Yong Zhao, Fengyun Chu, Huasong Chang, Hongchao Zhu, Jiahui Lu, Fuzhen Zhang, Xue Liang, Xingyu Li, Song Wang, Yuwei Gao, Hongbin He

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the …

Biosynthesis Of Chlorophyll And Other Isoprenoids In The Plastid Of Red Grape Berry Skins, António Teixeira, Henrique Noronha, Sarah Frusciante, Gianfranco Diretto, Hernâni Gerós

Faculty, Staff and Student Publications

Despite current knowledge showing that fruits like tomato and grape berries accumulate different components of the light reactions and Calvin cycle, the role of green tissues in fruits is not yet fully understood. In mature tomato fruits, chlorophylls are degraded and replaced by carotenoids through the conversion of chloroplasts in chromoplasts, while in red grape berries, chloroplasts persist at maturity and chlorophylls are masked by anthocyanins. To study isoprenoid and lipid metabolism in grape skin chloroplasts, metabolites of enriched organelle fractions were analyzed by high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and the expression of key genes was evaluated by real-time …

Biomarkers For Dementia In Latin American Countries: Gaps And Opportunities, Mario A Parra, Paulina Orellana, Tomas Leon, Cabello G Victoria, Fernando Henriquez, Rodrigo Gomez, Constanza Avalos, Andres Damian, Andrea Slachevsky, Agustin Ibañez, Henrik Zetterberg, Betty M Tijms, Jennifer S Yokoyama, Stefanie D Piña-Escudero, J Nicholas Cochran, Diana L Matallana, Daisy Acosta, Ricardo Allegri, Bianca P Arias-Suárez, Bernardo Barra, Maria Isabel Behrens, Sonia M D Brucki, Geraldo Busatto, Paulo Caramelli, Sheila Castro-Suarez, Valeria Contreras, Nilton Custodio, Sergio Dansilio, Myriam De La Cruz-Puebla, Leonardo Cruz De Souza, Monica M Diaz, Lissette Duque, Gonzalo A Farías, Sergio T Ferreira, Nahuel Magrath Guimet, Ana Kmaid, David Lira, Francisco Lopera, Beatriz Mar Meza, Eliane C Miotto, Ricardo Nitrini, Alberto Nuñez, Santiago O'Neill, John Ochoa, Maritza Pintado-Caipa, Elisa De Paula França Resende, Shannon Risacher, Luz Angela Rojas, Valentina Sabaj, Lucas Schilling, Allis F Sellek, Ana Sosa, Leonel T Takada, Antonio L Teixeira, Martha Unaucho-Pilalumbo, Claudia Duran-Aniotz

Faculty, Staff and Student Publications

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a …

Inhibition Of Myeloperoxidase Enhances Immune Checkpoint Therapy For Melanoma, Tracy W Liu, Seth T Gammon, Ping Yang, Wencai Ma, Jing Wang, David Piwnica-Worms

Faculty, Staff and Student Publications

BACKGROUND: The presence of a highly immunosuppressive tumor microenvironment has limited the success of immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production of reactive oxygen species are critical drivers of this immunosuppressive tumor microenvironment. Strategies to limit these immune suppressing myeloid cells are needed to enhance response to ICT.

METHODS: To evaluate the contribution of myeloperoxidase (MPO), a myeloid lineage-restricted enzyme and a major source of reactive oxygen species, to mediating ICT response, we compared treatment outcome and immune composition in wild-type, MPO-deficient (

RESULTS: Tumor growth and survival studies demonstrated that either host deficiency (

CONCLUSION: …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Danesh H Sopariwala, Andrea S Rios, Guangsheng Pei, Anirban Roy, Meiricris Tomaz Da Silva, Hao Thi Thu Nguyen, Addison Saley, Rachel Van Drunen, Anastasia Kralli, Kristin Mahan, Zhongming Zhao, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen-related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle-specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild-type (WT) littermates. RNA-seq analysis …

Energy Intake At The Intersection Of The Clock And Ageing, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

A Complete Methyl-Lysine Binding Aromatic Cage Constructed By Two Domains Of Phf2, John R Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T Bedford, Xiaodong Cheng

Faculty, Staff and Student Publications

The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR2TK4) and VRK1 (PR2VK4) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (KD values) of 160 nM and 42 nM, …

Ampk Regulates Homeostasis Of Invasion And Viability In Trophoblasts By Redirecting Glucose Metabolism: Implications For Pre-Eclampsia, Ping Xu, Yangxi Zheng, Jiujiang Liao, Mingyu Hu, Yike Yang, Baozhen Zhang, Mark D Kilby, Huijia Fu, Yamin Liu, Fumei Zhang, Liling Xiong, Xiyao Liu, Huili Jin, Yue Wu, Jiayu Huang, Tingli Han, Li Wen, Rufei Gao, Yong Fu, Xiujun Fan, Hongbo Qi, Philip N Baker, Chao Tong

Faculty, Staff and Student Publications

Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS). Trophoblast-specific AMPKα1-deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle-delivered A769662. Trophoblast glucose uptake was measured by 2-NBDG and 2-deoxy-d-[

Adjuvant 5-Fluorouracil/Leucovorin, Capecitabine, And Oxaliplatin-Related Regimens For Stage Ii/Iii Colon Cancer Patients 66 Years Or Older, Emily Jones, Zhigang Duan, Thinh T Nguyen, Sharon H Giordano, Hui Zhao

Faculty, Staff and Student Publications

Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FU/LV), capecitabine, and adding oxaliplatin to 5-FU/LV or capecitabine (FLOX/OX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used …

Superficial Low-Grade Fibromyxoid Sarcoma, Shira Ronen, Jennifer S Ko, Brian P Rubin, Scott E Kilpatrick, Wei-Lien Wang, Alexander J Lazar, John R Goldblum, Steven D Billings

Faculty, Staff and Student Publications

Background: Low-grade fibromyxoid sarcoma (LGFMS) typically involves deep soft tissue (beneath the fascia) of the proximal extremities and trunk. Long-term follow-up has shown a high rate of local recurrence, metastasis, and death. To the best of our knowledge, there is only one previous large series focusing on superficial LGFMS suggesting superficial tumors are disproportionately more common in children and may have a better prognosis. Our study's primary goals are to confirm these findings and increase general awareness that LGFMS may arise in superficial soft tissue.

Methods: We retrieved our cases of superficial LGFMS diagnosed between 2008 and 2020. Available slides …

Cotargeting Of Btk And Malt1 Overcomes Resistance To Btk Inhibitors In Mantle Cell Lymphoma, Vivian Changying Jiang, Yang Liu, Junwei Lian, Shengjian Huang, Alexa Jordan, Qingsong Cai, Ruitao Lin, Fangfang Yan, Joseph Mcintosh, Yijing Li, Yuxuan Che, Zhihong Chen, Jovanny Vargas, Maria Badillo, John Nelson Bigcal, Heng-Huan Lee, Wei Wang, Yixin Yao, Lei Nie, Christopher R Flowers, Michael Wang

Faculty, Staff and Student Publications

Bruton's tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11-knockout cells showed antitumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK/CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout …

Azacitidine Monotherapy In Patients With Treatment-Naïve Higher-Risk Myelodysplastic Syndrome: A Systematic Literature Review And Meta-Analysis, Ken Hasegawa, Andrew H Wei, Guillermo Garcia-Manero, Naval G Daver, Nishanthan Rajakumaraswamy, Shahed Iqbal, Rebecca J Chan, Hao Hu, Preston Tse, Jiajun Yan, Michael J Zoratti, Feng Xie, David A Sallman

Faculty, Staff and Student Publications

Background: The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.

Materials and methods: We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for …

Improved Benefit Of Continuing Luspatercept Therapy: Sub-Analysis Of Patients With Lower-Risk Mds In The Medalist Study, Ulrich Germing, Pierre Fenaux, Uwe Platzbecker, Rena Buckstein, Valeria Santini, María Díez-Campelo, Aylin Yucel, Derek Tang, Shannon Fabre, George Zhang, Roberto Zoffoli, Xianwei Ha, Dimana Miteva, Christina Hughes, Rami S Komrokji, Amer M Zeidan, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Red blood cell transfusion independence (RBC-TI) is an important goal in treating lower-risk myelodysplastic syndromes with ring sideroblasts. In the phase 3 MEDALIST study, RBC-TI of ≥ 8 weeks was achieved by significantly more luspatercept- versus placebo-treated patients in the first 24 weeks of treatment. In this post hoc analysis, we evaluated RBC transfusion units and visits based on patients' baseline transfusion burden level and the clinical benefit of luspatercept treatment beyond week 25 in initial luspatercept nonresponders (patients who did not achieve RBC-TI ≥ 8 weeks by week 25) but continued luspatercept up to 144 weeks. RBC transfusion burden, …

Author Correction: Analyses Of Non-Coding Somatic Drivers In 2,658 Cancer Whole Genomes, Esther Rheinbay, Morten Muhlig Nielsen, Federico Abascal, Jeremiah A Wala, Ofer Shapira, Grace Tiao, Henrik Hornshøj, Julian M Hess, Randi Istrup Juul, Ziao Lin, Lars Feuerbach, Radhakrishnan Sabarinathan, Tobias Madsen, Jaegil Kim, Loris Mularoni, Shimin Shuai, Andrés Lanzós, Carl Herrmann, Yosef E Maruvka, Ciyue Shen, Samirkumar B Amin, Pratiti Bandopadhayay, Johanna Bertl, Keith A Boroevich, John Busanovich, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, David Craft, Priyanka Dhingra, Klev Diamanti, Nuno A Fonseca, Abel Gonzalez-Perez, Qianyun Guo, Mark P Hamilton, Nicholas J Haradhvala, Chen Hong, Keren Isaev, Todd A Johnson, Malene Juul, Andre Kahles, Abdullah Kahraman, Youngwook Kim, Jan Komorowski, Kiran Kumar, Sushant Kumar, Donghoon Lee, Kjong-Van Lehmann, Yilong Li, Eric Minwei Liu, Lucas Lochovsky, Keunchil Park, Oriol Pich, Nicola D Roberts, Gordon Saksena, Steven E Schumacher, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Chip Stewart, David Tamborero, Jose M C Tubio, Husen M Umer, Liis Uusküla-Reimand, Claes Wadelius, Lina Wadi, Xiaotong Yao, Cheng-Zhong Zhang, Jing Zhang, James E Haber, Asger Hobolth, Marcin Imielinski, Manolis Kellis, Michael S Lawrence, Christian Von Mering, Hidewaki Nakagawa, Benjamin J Raphael, Mark A Rubin, Chris Sander, Lincoln D Stein, Joshua M Stuart, Tatsuhiko Tsunoda, David A Wheeler, Rory Johnson, Jüri Reimand, Mark Gerstein, Ekta Khurana, Peter J Campbell, Núria López-Bigas, Pcawg Drivers And Functional Interpretation Working Group, Pcawg Structural Variation Working Group, Joachim Weischenfeldt, Rameen Beroukhim, Iñigo Martincorena, Jakob Skou Pedersen, Gad Getz

Faculty, Staff and Student Publications

No abstract provided.

Base Editing Correction Of Hypertrophic Cardiomyopathy In Human Cardiomyocytes And Humanized Mice, Andreas C Chai, Miao Cui, Francesco Chemello, Hui Li, Kenian Chen, Wei Tan, Ayhan Atmanli, John R Mcanally, Yu Zhang, Lin Xu, Ning Liu, Rhonda Bassel-Duby, Eric N Olson

Faculty, Staff and Student Publications

The most common form of genetic heart disease is hypertrophic cardiomyopathy (HCM), which is caused by variants in cardiac sarcomeric genes and leads to abnormal heart muscle thickening. Complications of HCM include heart failure, arrhythmia and sudden cardiac death. The dominant-negative c.1208G>A (p.R403Q) pathogenic variant (PV) in β-myosin (MYH7) is a common and well-studied PV that leads to increased cardiac contractility and HCM onset. In this study we identify an adenine base editor and single-guide RNA system that can efficiently correct this human PV with minimal bystander editing and off-target editing at selected sites. We show that delivery of …

Changes In Availability Of And Prices For Shoppable Services At Us News And World Report Honor Roll Hospitals: A Longitudinal Cross-Sectional Study, Peter Cram, Elliot Cram, Joseph Antos, Dean F Sittig, Ajay Anand, Yue Li

Faculty, Staff and Student Publications

No abstract provided.

Post-Irradiation Intratumoral Heterogeneity Modulates Response To Immune Checkpoint Inhibition Therapy In A Murine Melanoma Model, Jie Wang, Shivani Sud, Yanli Qu, Liantao Li, Jiajie Zhang, David Marron, Nicole Michelle Knape, Isaiah James Kim, Kyle Thomas Wagner, Tian Zhang, Yuxia Zhao, Genyan Guo, Andrew Z Wang

Faculty, Staff and Student Publications

Purpose: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI.

Experimental design: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated …

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Faculty, Staff and Student Publications

No abstract provided.

Pkr Induces Tgf-Β And Limits Oncolytic Immune Therapy, Bangxing Hong, Upasana Sahu, Matthew P Mullarkey, Evan Hong, Guangsheng Pei, Yuanqing Yan, Yoshihiro Otani, Yeshavanth Banasavadi-Siddegowda, Huihui Fan, Zhongming Zhao, Jianhua Yu, Michael A Caligiuri, Balveen Kaur

Faculty, Staff and Student Publications

BACKGROUND: Mammalian cells have developed multiple intracellular mechanisms to defend against viral infections. These include RNA-activated protein kinase (PKR), cyclic GMP-AMP synthase and stimulation of interferon genes (cGAS-STING) and toll-like receptor-myeloid differentiation primary response 88 (TLR-MyD88). Among these, we identified that PKR presents the most formidable barrier to oncolytic herpes simplex virus (oHSV) replication in vitro.

METHODS: To elucidate the impact of PKR on host responses to oncolytic therapy, we generated a novel oncolytic virus (oHSV-shPKR) which disables tumor intrinsic PKR signaling in infected tumor cells.

RESULTS: As anticipated, oHSV-shPKR resulted in suppression of innate antiviral immunity and improves virus …

Author Correction: The Evolutionary History Of 2,658 Cancers, Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C Dentro, Santiago Gonzalez, Daniel Rosebrock, Thomas J Mitchell, Yulia Rubanova, Pavana Anur, Kaixian Yu, Maxime Tarabichi, Amit Deshwar, Jeff Wintersinger, Kortine Kleinheinz, Ignacio Vázquez-García, Kerstin Haase, Lara Jerman, Subhajit Sengupta, Geoff Macintyre, Salem Malikic, Nilgun Donmez, Dimitri G Livitz, Marek Cmero, Jonas Demeulemeester, Steven Schumacher, Yu Fan, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Paul C Boutros, David D Bowtell, Hongtu Zhu, Gad Getz, Marcin Imielinski, Rameen Beroukhim, S Cenk Sahinalp, Yuan Ji, Martin Peifer, Florian Markowetz, Ville Mustonen, Ke Yuan, Wenyi Wang, Quaid D Morris, Paul T Spellman, David C Wedge, Peter Van Loo

Faculty, Staff and Student Publications

No abstract provided.

Phase Ii Trial Of Weekly Erlotinib Dosing To Reduce Duodenal Polyp Burden Associated With Familial Adenomatous Polyposis, N Jewel Samadder, Nathan Foster, Ryan P Mcmurray, Carol A Burke, Elena Stoffel, Priyanka Kanth, Rohit Das, Marcia Cruz-Correa, E Vilar, Gautam Mankaney, Navtej Buttar, Selvi Thirumurthi, Danielle K Turgeon, Michael Sossenheimer, Michelle Westover, Ellen Richmond, Asad Umar, Gary Della'zanna, Luz M Rodriguez, Eva Szabo, David Zahrieh, Paul J Limburg

Faculty, Staff and Student Publications

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Design, setting and participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres.

Exposures: Participants self-administered 350 mg of erlotinib …

Cost Of Failure To Achieve Textbook Outcomes: Association Of Insurance Type With Outcomes And Cumulative Cost For Inpatient Surgery, Michael A Jacobs, Jeongsoo Kim, Jasmine C Tetley, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Background: Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization.

Study design: This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions.

Results: Cases were performed …

Reply To J Widder, Steven J Chmura, Wendy A Woodward, Julia R White

Faculty, Staff and Student Publications

No abstract provided.

Optimized Decision Support For Selection Of Transoral Robotic Surgery Or (Chemo)Radiation Therapy Based On Posttreatment Swallowing Toxicity, Mehdi Hemmati, Carly Barbon, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Neil D Gross, Ryan P Goepfert, Stephen Y Lai, Katherine A Hutcheson, Andrew J Schaefer, Clifton D Fuller, Md Anderson Head And Neck Cancer Symptom Working Group Affiliations Expand

Faculty, Staff and Student Publications

BACKGROUND: A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors.

METHODS: A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging …

Long-Term Effects Of Obstructive Sleep Apnea And Its Treatment On Open-Angle Glaucoma: A Big-Data Cohort Study, Tae-Eun Lee, Jong Seung Kim, Sang Woo Yeom, Min Gyu Lee, Jong Hwan Lee, Haeng-Jin Lee

Faculty, Staff and Student Publications

STUDY OBJECTIVES: The relationship between open-angle glaucoma (OAG) and obstructive sleep apnea (OSA) is unclear. The long-term risk for OAG after OSA diagnosis has not been investigated. Therefore, we assessed the risk for OAG among patients with OSA over a 12-year follow-up period using nationwide, population-based data.

METHODS: The OSA group was randomly selected from among 3.5 million individuals registered with the National Health Insurance Service. The non-OSA group was obtained through propensity score matching considering several variables. The primary endpoint was glaucoma diagnosis.

RESULTS: The OSA and non-OSA groups both included 6,369 individuals. The overall hazard ratio for OAG …

Pyridoxamine Treatment Ameliorates Large Artery Stiffening And Cerebral Artery Endothelial Dysfunction In Old Mice, Emily H Reeve, Elise K Kronquist, Julia R Wolf, Byron Lee, Aleena Khurana, Hanson Pham, Abigail E Cullen, Jessica A Peterson, Antonio Meza, R Colton Bramwell, Laura Villasana, Daniel R Machin, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old …

Dual Beam-Current Transformer Design For Monitoring And Reporting Of Electron Ultra-High Dose Rate (Flash) Beam Parameters, Kevin Liu, Allison Palmiero, Nitish Chopra, Brett Velasquez, Ziyi Li, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

PURPOSE: To investigate the usefulness and effectiveness of a dual beam-current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real-time, and to inform on the usefulness of this design for future eFLASH beam control.

METHODS: Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam …

E Pluribus Unum: Prospective Acceptability Benchmarking From The Contouring Collaborative For Consensus In Radiation Oncology Crowdsourced Initiative For Multiobserver Segmentation, Diana Lin, Kareem A Wahid, Benjamin E Nelms, Renjie He, Mohammed A Naser, Simon Duke, Michael V Sherer, John P Christodouleas, Abdallah S R Mohamed, Michael Cislo, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Purpose: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement.

Approach: Participants who contoured ≥1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. …

Gender Bias In The Evaluation Of Surgical Performance: Results Of A Prospective Randomized Trial, Mara B Antonoff, Hope Feldman, Jessica G Y Luc, Paula I Iaeger, M Laura Rubin, Liang Li, Ara A Vaporciyan

Faculty, Staff and Student Publications

Objective: The study aims to determine the influence of trainee gender on assessments of coronary anastomosis performance.

Summary of background data: Understanding the impact of gender bias on the evaluation of trainees may enable us to identify and utilize assessment tools that are less susceptible to potential bias.

Methods: Cardiothoracic surgeons were randomized to review the video performance of trainees who were described by either male or female pronouns. All participants viewed the same video of a coronary anastomosis and were asked to grade technique using either a Checklist or Global Rating Scale (GRS). Effect of trainee gender on scores …

American Radium Society (Ars) Appropriate Use Criteria (Auc) For Extrahepatic Cholangiocarcinoma, Leila T Tchelebi, Krishan R Jethwa, Anna T Levy, Christopher J Anker, Timothy Kennedy, Elliot Grodstein, Christopher L Hallemeier, Salma K Jabbour, Ed Kim, Rachit Kumar, Percy Lee, William Small, Vonetta M Williams, Navesh Sharma, Suzanne Russo

Faculty, Staff and Student Publications

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic …