Medicine and Health Sciences Commons^™

Bladder-Sparing Treatment In Patients With Bacillus Calmette-Guerin-Unresponsive Non-Muscle-Invasive Bladder Cancer: An Analysis Of Long-Term Survival Outcomes, Wei Shen Tan, Valentina Grajales, Roberto Contieri, Patrick Hensley, Kelly Bree, Pavlos Msaouel, Charles C Guo, Graciela M Nogueras-Gonzalez, Neema Navai, Colin P Dinney, Ashish M Kamat

Faculty, Staff and Student Publications

BACKGROUND: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1-2 yr.

OBJECTIVE: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST.

DESIGN SETTING AND PARTICIPANTS: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated.

INTERVENTION: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS).

RESULTS AND LIMITATIONS: In total, 114 patients with a median follow-up …

Estrogen-Related Receptor Signaling In Skeletal Muscle Fitness, Danesh Sopariwala, Hao Nguyen, Vihang Narkar

Faculty, Staff and Student Publications

Skeletal muscle is a highly plastic tissue that can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors, and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On …

Plasma Cell Myeloma With Ras/Braf Mutations Is Frequently Associated With A Complex Karyotype, Advanced Stage Disease, And Poorer Prognosis, Nianyi Li, Pei Lin, Zhuang Zuo, M James You, Wen Shuai, Robert Orlowski, Elisabet E Manasanch, Shaoying Li, Jie Xu, Sofia Garces, Fatima Zahra Jelloul, Zhenya Tang, Wei Wang, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

BACKGROUND: Mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high-risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results.

METHODS: We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF-mutated myeloma, and compare with 79 patients without any mutations.

RESULTS: We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF-mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and …

Exploring The Interactions Between Sars-Cov-2 And Host Proteins, Sojan Shrestha

School of Biological Sciences: Dissertations, Theses, and Student Research

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic, Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is considered to be of zoonotic origin; it originated in non-human animals and was transmitted to humans. Since the early stage of the pandemic, however, the evidence of transmissions from humans to animals (reverse zoonoses) has been found in multiple animal species including mink, white-tailed deer, and pet and zoo animals. Furthermore, secondary zoonotic events of SARS-CoV-2, transmissions from animals to humans, have been also reported. It is suggested that non-human hosts can act as SARS-CoV-2 reservoirs where accumulated …

Sox11 Is An Effective Discriminatory Marker, When Used In Conjunction With Ck20 And Ttf1, For Merkel Cell Carcinoma: Comparative Analysis Of Sox11, Ck20, Pax5, And Ttf1 Expression In Merkel Cell Carcinoma And Pulmonary Small Cell Carcinoma, Woo Cheal Cho, Kaitlin Vanderbeck, Priyadharsini Nagarajan, Denái R Milton, Pavandeep Gill, Wei-Lien Wang, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Phyu P Aung

Faculty, Staff and Student Publications

Context.—: Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1- in MCC and CK20-/TTF1+ in PSmCC).

Objective.—: To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC.

Design.—: SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. …

Intensity Modulated Proton Arc Therapy Via Geometry-Based Energy Selection For Ependymoma, Wenhua Cao, Yupeng Li, Xiaodong Zhang, Falk Poenisch, Pablo Yepes, Narayan Sahoo, David Grosshans, Susan Mcgovern, G Brandon Gunn, Steven J Frank, Xiaorong R Zhu

Faculty, Staff and Student Publications

PURPOSE: We developed and tested a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources similar to those for regular intensity-modulated proton therapy (IMPT) plans and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries.

METHODS: Our IMPAT planning method consists of a geometry-based energy selection step with major scanning spot contributions as inputs computed using ray-tracing and single-Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle …

Eliminating Breast Surgery For Invasive Cancer With Exceptional Response To Neoadjuvant Systemic Therapy: Prospective Multicenter Clinical Trial Planned Initial Feasibility Endpoint, Helen M Johnson, Vicente Valero, Wei T Yang, Benjamin D Smith, Savitri Krishnamurthy, Yu Shen, Heather Lin, Anthony Lucci, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

Background: Response to neoadjuvant systemic therapy (NST) for breast cancer enables tailoring of subsequent therapy. Image-guided breast biopsy after NST can accurately predict a pathologic complete response (pCR). The feasibility phase of the clinical trial reported here assesses omission of breast surgery followed by radiotherapy in terms of local recurrence before trial expansion.

Study design: Women with unicentric, cT1-2 N0-1 M0 triple-negative (TNBC) or human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) cancer with < 2 cm residual disease on post-NST imaging were eligible to enroll. If no residual invasive or in situ disease was identified by image-guided, vacuum-assisted core biopsy (VACB), breast surgery was omitted, and radiotherapy delivered. The primary endpoint for the feasibility phase was ipsilateral breast tumor recurrence at 6 months. If any recurrence occurred during the feasibility phase the trial would halt.

Results: Thirteen patients were enrolled from March 2017 to October 2018. The mean age was 60.8 years (range 51 to 75) and most patients were …

Carboplatin Dosing In The Treatment Of Ovarian Cancer: An Nrg Oncology Group Study, Aaron M Praiss, Austin Miller, Judith Smith, Stuart M Lichtman, Michael Bookman, Carol Aghajanian, Paul Sabbatini, Floor Backes, David E Cohn, Peter Argenta, Michael Friedlander, Michael J Goodheart, David G Mutch, David M Gershenson, Krishnansu S Tewari, Robert M Wenham, Andrea E Wahner Hendrickson, Roger B Lee, Heidi Gray, Angeles Alvarez Secord, Linda Van Le, Roisin E O'Cearbhaill

Faculty, Staff and Student Publications

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity …

Association Of Second-Generation Antiandrogens With Cognitive And Functional Toxic Effects In Randomized Clinical Trials: A Systematic Review And Meta-Analysis, Malgorzata K Nowakowska, Rachel M Ortega, Mackenzie R Wehner, Kevin T Nead

Faculty, Staff and Student Publications

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed.

Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects.

Data sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022).

Study selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, …

Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome, Melissa R Hines, Tristan E Knight, Kevin O Mcnerney, Mark B Leick, Tania Jain, Sairah Ahmed, Matthew J Frigault, Joshua A Hill, Michael D Jain, William T Johnson, Yi Lin, Kris M Mahadeo, Gabriela M Maron, Rebecca A Marsh, Sattva S Neelapu, Sarah Nikiforow, Amanda K Ombrello, Nirav N Shah, Aimee C Talleur, David Turicek, Anant Vatsayan, Sandy W Wong, Marcela V Maus, Krishna V Komanduri, Nancy Berliner, Jan-Inge Henter, Miguel-Angel Perales, Noelle V Frey, David T Teachey, Matthew J Frank, Nirali N Shah

Faculty, Staff and Student Publications

T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) T cell therapy. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusion are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal …

Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions, Alex K Bryant, Zoey Chopra, Donna M Edwards, Adam S Whalley, Brian G Bazzell, Julie A Moeller, Michael J Kelley, A Mark Fendrick, Eve A Kerr, Nithya Ramnath, Michael D Green, Timothy P Hofer, Garth W Strohbehn

Faculty, Staff and Student Publications

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at "one-size-fits-all" flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug …

A Cre Driver Line For Genetic Targeting Of Kappa Opioid Receptor Expressing Cells, Franciely Paliarin, Chelsea Duplantis, Andrea F Jones, Jessica Cucinello-Ragland, Samhita Basavanhalli, Emily Blaze, Evan Doré, Anna Isabella Neel, Haiguo Sun, Rong Chen, Scott Edwards, Nicholas W Gilpin, Robert O Messing, Rajani Maiya

Faculty, Staff and Student Publications

Here we describe the generation and characterization of a Cre knock-in mouse line that harbors a Cre insertion in the 3′UTR of the κ opioid receptor gene (Oprk1) locus and provides genetic access to populations of κ opioid receptor (KOR)-expressing neurons throughout the brain. Using a combination of techniques including RNA in situ hybridization and immunohistochemistry, we report that Cre is expressed with high fidelity in KOR-expressing cells throughout the brain in this mouse line. We also provide evidence that Cre insertion does not alter basal KOR function. Baseline anxiety-like behaviors and nociceptive thresholds are unaltered in Oprk1-Cre …

Author Correction: Multiscale Reorganization Of The Genome Following Dna Damage Facilitates Chromosome Translocations Via Nuclear Actin Polymerization, Jennifer Zagelbaum, Allana Schooley, Junfei Zhao, Benjamin R Schrank, Elsa Callen, Shan Zha, Max E Gottesman, André Nussenzweig, Raul Rabadan, Job Dekker, Jean Gautier

Faculty, Staff and Student Publications

No abstract provided.

Invited Commentary: Mri Clear Cell Likelihood Score For Indeterminate Solid Renal Masses: Is There A Path For Broad Clinical Adoption?, Ivan Pedrosa

Faculty, Staff and Student Publications

No abstract provided.

Interferon Signaling Promotes Tolerance To Chromosomal Instability During Metastatic Evolution In Renal Cancer, Luigi Perelli, Federica Carbone, Li Zhang, Justin K Huang, Courtney Le, Hania Khan, Francesca Citron, Edoardo Del Poggetto, Tony Gutschner, Hideo Tomihara, Melinda Soeung, Rosalba Minelli, Sanjana Srinivasan, Michael Peoples, Truong Nguyen Anh Lam, Sebastian Lundgren, Ruohan Xia, Cihui Zhu, Alaa M T Mohamed, Jianhua Zhang, Kanishka Sircar, Alessandro Sgambato, Jianjun Gao, Eric Jonasch, Giulio F Draetta, Andrew Futreal, Ziad Bakouny, Eliezer M Van Allen, Toni Choueiri, Sabina Signoretti, Pavlos Msaouel, Kevin Litchfield, Samra Turajlic, Linghua Wang, Ying Bei Chen, Renzo G Di Natale, A Ari Hakimi, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Christopher A Bristow, Nizar M Tannir, Alessandro Carugo, Giannicola Genovese

Faculty, Staff and Student Publications

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect …

Examining Mechanisms For Voltage-Sensitive Calcium Channel-Mediated Secretion Events In Bone Cells, Perla C Reyes Fernandez, Christian S Wright, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

In addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca2+)-mediated secretion of pleiotropic paracrine and endocrine factors, including those produced in bone. Influx of Ca2+ through VSCCs activates intracellular signaling pathways to modulate a variety of cellular processes that include cell proliferation, differentiation, and bone adaptation in response to mechanical stimuli. Less well understood is the role of VSCCs in the control of bone and calcium homeostasis mediated through secreted factors. In this review, we discuss the various functions of VSCCs in skeletal cells as regulators of Ca2+ dynamics and …

Resection Cavity Auto-Contouring For Patients With Pediatric Medulloblastoma Using Only Ct Information, Soleil Hernandez, Callistus Nguyen, Skylar Gay, Jack Duryea, Rebecca Howell, David Fuentes, Jeannette Parkes, Hester Burger, Carlos Cardenas, Arnold C Paulino, Julianne Pollard-Larkin, Laurence Court

Faculty, Staff and Student Publications

PURPOSE: Target delineation for radiation therapy is a time-consuming and complex task. Autocontouring gross tumor volumes (GTVs) has been shown to increase efficiency. However, there is limited literature on post-operative target delineation, particularly for CT-based studies. To this end, we trained a CT-based autocontouring model to contour the post-operative GTV of pediatric patients with medulloblastoma.

METHODS: One hundred four retrospective pediatric CT scans were used to train a GTV auto-contouring model. Eighty patients were then preselected for contour visibility, continuity, and location to train an additional model. Each GTV was manually annotated with a visibility score based on the number …

The Promise And Future Of Radiomics For Personalized Radiotherapy Dosing And Adaptation, Rachel B Ger, Lise Wei, Issam El Naqa, Jing Wang

Faculty, Staff and Student Publications

Quantitative image analysis, also known as radiomics, aims to analyze large-scale quantitative features extracted from acquired medical images using hand-crafted or machine-engineered feature extraction approaches. Radiomics has great potential for a variety of clinical applications in radiation oncology, an image-rich treatment modality that utilizes computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for treatment planning, dose calculation, and image guidance. A promising application of radiomics is in predicting treatment outcomes after radiotherapy such as local control and treatment-related toxicity using features extracted from pretreatment and on-treatment images. Based on these individualized predictions of treatment outcomes, radiotherapy …

Characteristics, Treatment, And Outcome Of Diverticulitis After Immune Checkpoint Inhibitor Treatment In Patients With Malignancies, Austin R Thomas, Mostafa Eyada, Miho Kono, Krishnavathana Varatharajalu, Yang Lu, Guofan Xu, Kavea Panneerselvam, Malek Shatila, Mehmet Altan, Jennifer Wang, John A Thompson, Hao Chi Zhang, Muhammad Ali Khan, Gottumukkala S Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Student Publications

Purpose: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment.

Methods: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups.

Results: 77 eligible patients were included: 63 patients developed …

Route Of Delivery Does Not Impact Postnatal Surgical Morbidity In Pregnancies Affected By Fetal Achondroplasia, Bobby K Brar, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Lorena Dujmusic, Mary E Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Janet M Legare, Julie E Hoover-Fong

Faculty, Staff and Student Publications

Purpose: Pregnancies affected by maternal or fetal achondroplasia present unique challenges. The optimal route of delivery in fetuses with achondroplasia has not been established. Our objective was to determine whether the route of delivery affects postnatal achondroplasia-related surgical burden.

Methods: We conducted a secondary analysis of Achondroplasia Natural History Study (CLARITY), which is a multicenter natural history cohort study of patients with achondroplasia. Achondroplasia-related surgical morbidity, which we defined as the need for one or more postnatal achondroplasia-related surgeries, was assessed in relation to the route of delivery and whether the mother also had achondroplasia. Rate of each individual surgery …

Mrtx-500 Phase 2 Trial: Sitravatinib With Nivolumab In Patients With Nonsquamous Nsclc Progressing On Or After Checkpoint Inhibitor Therapy Or Chemotherapy, Kai He, David Berz, Shirish M Gadgeel, Wade T Iams, Debora S Bruno, Collin M Blakely, Alexander I Spira, Manish R Patel, David M Waterhouse, Donald A Richards, Anthony Pham, Robert Jotte, David S Hong, Edward B Garon, Anne Traynor, Peter Olson, Lisa Latven, Xiaohong Yan, Ronald Shazer, Ticiana A Leal

Faculty, Staff and Student Publications

Introduction: Sitravatinib, a receptor tyrosine kinase inhibitor targeting TYRO3, AXL, MERTK receptors, and vascular epithelial growth factor receptor 2, can shift the tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPIs) may augment antitumor activity.

Methods: The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2 or 4 wk) in patients with advanced nonsquamous NSCLC who progressed on or after previous CPI (CPI-experienced) or chemotherapy (CPI-naive). CPI-experienced patients had a previous clinical benefit (PCB) (complete response, partial response, or stable disease for at least 12 weeks then disease progression) or no PCB (NPCB) …

Ai In Drug Discovery And Its Clinical Relevance, Rizwan Qureshi, Muhammad Irfan, Taimoor Muzaffar Gondal, Sheheryar Khan, Jia Wu, Muhammad Usman Hadi, John Heymach, Xiuning Le, Hong Yan, Tanvir Alam

Faculty, Staff and Student Publications

The COVID-19 pandemic has emphasized the need for novel drug discovery process. However, the journey from conceptualizing a drug to its eventual implementation in clinical settings is a long, complex, and expensive process, with many potential points of failure. Over the past decade, a vast growth in medical information has coincided with advances in computational hardware (cloud computing, GPUs, and TPUs) and the rise of deep learning. Medical data generated from large molecular screening profiles, personal health or pathology records, and public health organizations could benefit from analysis by Artificial Intelligence (AI) approaches to speed up and prevent failures in …

Snakes And Ladders: A Potential Therapy Of Hepatocyte Growth Factor And Pigment Epithelium-Derived Factor In Pulmonary Hypertension, Joseph M Zambelas, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

No abstract provided.

Early Stage Gastric Adenocarcinoma: Clinical And Molecular Landscapes, Yuki Hirata, Ayesha Noorani, Shumei Song, Linghua Wang, Jaffer A Ajani

Faculty, Staff and Student Publications

Gastric adenocarcinoma, even when diagnosed at an early (localized) disease stage, poses a major health-care burden with cure rates that remain unsatisfactorily low, particularly in Western countries. This lack of progress reflects, among other aspects, the impracticality of early diagnosis, considerable variations in therapeutic approaches that is partly based on regional preferences, and the ingrained heterogeneity of gastric adenocarcinoma cells and their associated tumour microenvironment (TME). Clinical trials have long applied empirical interventions with the assumption that all early stage gastric adenocarcinomas are alike. Despite certain successes, the shortcomings of these approaches can potentially be overcome by targeting the specific …

Reducing The Production Of Acrylamide During The Roasting Of Balloon Flower Roots In Consumer Appliances And Industrial Equipment, Min Gyu Lee, Hyebin Han, Seung Hwan Ham, Suyoon Lee, Young Jin Choi, Jungwoo Hahn

Faculty, Staff and Student Publications

This study aimed to determine what conditions were needed to reduce the production of acrylamide when balloon flower roots [Platycodon grandiflorum (Jacq. A. DC.)] were heated. The conditions of temperature, time, and the type of equipment (i.e., consumer appliance or industrial equipment) were the important variables in the experiment. The official criterion for a recommended standard of acrylamide in tea product is less than 1000 µg/kg as determined by the Ministry of Food and Drug Safety in South Korea. A response surface methodology was used to determine whether the heated samples met the safety requirements. The most significant condition …

Neoadjuvant Immunotherapy For Advanced, Resectable Non-Small Cell Lung Cancer: A Systematic Review And Meta-Analysis, Yajing Wu, Vivek Verma, Carl M Gay, Yujia Chen, Fei Liang, Qiang Lin, Jianing Wang, Wei Zhang, Zhouguang Hui, Min Zhao, Jun Wang, Joe Y Chang

Faculty, Staff and Student Publications

Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.

Methods: Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For …

Federated Benchmarking Of Medical Artificial Intelligence With Medperf, Alexandros Karargyris, Renato Umeton, Micah J Sheller, Alejandro Aristizabal, Johnu George, Anna Wuest, Sarthak Pati, Hasan Kassem, Maximilian Zenk, Ujjwal Baid, Prakash Narayana Moorthy, Alexander Chowdhury, Junyi Guo, Sahil Nalawade, Jacob Rosenthal, David Kanter, Maria Xenochristou, Daniel J Beutel, Verena Chung, Timothy Bergquist, James Eddy, Abubakar Abid, Lewis Tunstall, Omar Sanseviero, Dimitrios Dimitriadis, Yiming Qian, Xinxing Xu, Yong Liu, Rick Siow Mong Goh, Srini Bala, Victor Bittorf, Sreekar Reddy Puchala, Biagio Ricciuti, Soujanya Samineni, Eshna Sengupta, Akshay Chaudhari, Cody Coleman, Bala Desinghu, Gregory Diamos, Debo Dutta, Diane Feddema, Grigori Fursin, Xinyuan Huang, Satyananda Kashyap, Nicholas Lane, Indranil Mallick, Fets Consortium, Brats-2020 Consortium, Ai4safechole Consortium, Pietro Mascagni, Virendra Mehta, Cassiano Ferro Moraes, Vivek Natarajan, Nikola Nikolov, Nicolas Padoy, Gennady Pekhimenko, Vijay Janapa Reddi, G Anthony Reina, Pablo Ribalta, Abhishek Singh, Jayaraman J Thiagarajan, Jacob Albrecht, Thomas Wolf, Geralyn Miller, Huazhu Fu, Prashant Shah, Daguang Xu, Poonam Yadav, David Talby, Mark M Awad, Jeremy P Howard, Michael Rosenthal, Luigi Marchionni, Massimo Loda, Jason M Johnson, Spyridon Bakas, Peter Mattson

Faculty, Staff and Student Publications

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain. MedPerf focuses on enabling federated evaluation of AI models, by securely distributing them to different facilities, such as healthcare organizations. This process of bringing the model …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Tumor And Breast Activity Concentrations, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of

PURPOSE: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue

METHODS: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of …

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing For Craniomaxillofacial Bone Regeneration, Vasudev Vivekanand Nayak, Blaire V Slavin, Edmara T P Bergamo, Andrea Torroni, Christopher M Runyan, Roberto L Flores, F Kurtis Kasper, Simon Young, Paulo G Coelho, Lukasz Witek

Faculty, Staff and Student Publications

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as β-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific …

Effects Of A Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy On Physical Function Of Patients With Pancreatic Cancer: The Pancfit Randomized Clinical Trial, An T Ngo-Huang, Nathan H Parker, Lianchun Xiao, Keri L Schadler, Maria Q B Petzel, Laura R Prakash, Michael P Kim, Ching-Wei D Tzeng, Jeffrey E Lee, Naruhiko Ikoma, Robert A Wolff, Milind M Javle, Eugene J Koay, Shubham D Pant, Justin P Folloder, Xuemei Wang, Alicia M Cotto, Ye Rang Ju, Naveen Garg, Huamin Wang, Eduardo D Bruera, Karen M Basen-Engquist, Matthew H G Katz

Faculty, Staff and Student Publications

OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer.

BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer.

METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included …