Medicine and Health Sciences Commons^™

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 …

Development Of Cancer Surveillance Guidelines In Ataxia Telangiectasia: A Delphi-Based Consensus Survey Of International Experts, Renata Neves, Blanca De Dios Perez, Rafal Panek, Sumit Jagani, Sophie Wilne, Jayesh M Bhatt, Caterina Caputi, Emilia Cirillo, David J Coman, Gregor Dückers, Donald L Gilbert, Mary Kay Koenig, Lobna Mansour, Elizabeth Mcdermott, Micaela Pauni, Claudio Pignata, Susan L Perlman, Oscar Porras, Mariela Betina Porto, Katherine Schon, Pere Soler-Palacin, Sam Nick Russo, Masatoshi Takagi, Marc Tischkowitz, Claire Wainwright, Madhumita Dandapani, Cristine Glazebrook, Mohnish Suri, William P Whitehouse, Robert A Dineen

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T.

DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed …

Epilepsy Severity Is Associated With Head Circumference And Growth Rate In Infants With Tuberous Sclerosis Complex, Alexis Levine, Peter Davis, Bo Zhang, Jurriaan Peters, Rajna Filip-Dhima, Simon K Warfield, Anna Prohl, Jamie Capal, Darcy Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Mustafa Sahin

Faculty, Staff and Student Publications

BACKGROUND: Abnormal brain growth in tuberous sclerosis complex (TSC) reflects abnormalities in cellular proliferation and differentiation and results in epilepsy and other neurological manifestations. Head circumference (HC) as a proxy for brain volume may provide an easily tracked clinical measure of brain overgrowth and neurological disease burden. This study investigated the relationship between HC and epilepsy severity in infants with TSC.

METHODS: Prospective multicenter observational study of children from birth to three years with TSC. Epilepsy data were collected from clinical history, and HC was collected at study visits at age three, six, nine, 12, 18, 24, and 36 months. …

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 …

Inhibition Of Autophagy In Microglia And Macrophages Exacerbates Innate Immune Responses And Worsens Brain Injury Outcomes, Nivedita Hegdekar, Chinmoy Sarkar, Sabrina Bustos, Rodney M Ritzel, Marie Hanscom, Prarthana Ravishankar, Deepika Philkana, Junfang Wu, David J Loane, Marta M Lipinski

Faculty, Staff and Student Publications

Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) contributes to long-term tissue damage and poor functional outcomes. However, the mechanisms contributing to exacerbated inflammatory responses after brain injury remain poorly understood. Our previous work showed that macroautophagy/autophagy flux is inhibited in neurons following TBI in mice and contributes to neuronal cell death. In the present study, we demonstrate that autophagy is also inhibited in activated microglia and infiltrating macrophages, and that this potentiates injury-induced neuroinflammatory responses. Macrophage/microglia-specific knockout of the essential autophagy gene Becn1 led to overall increase in neuroinflammation after TBI. In particular, we observed excessive activation of …

The Genetics Of Primary Ciliary Dyskinesia In Puerto Rico, Paolo Zanoni, Katharina Steindl, Heinrich Sticht, Beatrice Oneda, Pascal Joset, Ivan Ivanovski, Anselm H C Horn, Elena M Cabello, Julia Laube, Markus Zweier, Alessandra Baumer, Anita Rauch, Nadia Khan

Faculty, Staff and Student Publications

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA …

Association Of Trauma Molecular Endotypes With Differential Response To Transfusion Resuscitation Strategies, Matthew R Thau, Ted Liu, Neha A Sathe, Grant E O'Keefe, Bryce R H Robinson, Eileen Bulger, Charles E Wade, Erin E Fox, John B Holcomb, W Conrad Liles, Ian B Stanaway, Carmen Mikacenic, Mark M Wurfel, Pavan K Bhatraju, Eric D Morrell

Faculty, Staff and Student Publications

IMPORTANCE: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies.

OBJECTIVE: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe …

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 …

Mird Pamphlet No 28, Part 1: Mirdcalc—A Software Tool For Medical Internal Radiation Dosimetry, Adam L Kesner, Lukas M Carter, Juan C Ocampo Ramos, Daniel Lafontaine, Edmond A Olguin, Justin L Brown, Bonnie President, Derek W Jokisch, Darrell R Fisher, Wesley E Bolch

Faculty, Staff and Student Publications

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, …

Difficult Or Impossible Facemask Ventilation In Children With Difficult Tracheal Intubation: A Retrospective Analysis Of The Pedi Registry, Annery G Garcia-Marcinkiewicz, Lisa K Lee, Bishr Haydar, John E Fiadjoe, Clyde T Matava, Pete G Kovatsis, James Peyton, Mary L Stein, Raymond Park, Brad M Taicher, Thomas W Templeton

Faculty, Staff and Student Publications

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a …

Thiazolidinedione Use And Retinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Glenn Jaffe, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

BACKGROUND: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

METHODS: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium …

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 …

Functional Assessment Of The Dural Lymphatic Vessels Using Dynamic Contrast Mri In Multiple Sclerosis, Refaat E Gabr, John A Lincoln, Khader M Hasan, Larry A Kramer

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance.

METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T …

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 …

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline, Anthony Patrizz, Ahmad El Hamamy, Michael Maniskas, Yashasvee Munshi, Louise Atadja, Hilda Ahnstedt, Matthew Howe, Fan Bu, Daniel K Mulkey, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS: Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were …

Immunometabolism At The Heart Of Cardiovascular Disease, Matthew Deberge, Rajesh Chaudhary, Samantha Schroth, Edward B Thorp

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Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. …

Prognostic Factors For Pediatric, Adolescent, And Young Adult Patients With Non-Dipg Grade 4 Gliomas: A Contemporary Pooled Institutional Experience, Jennifer K Matsui, Pamela K Allen, Haley K Perlow, Jason M Johnson, Arnold C Paulino, Mary Frances Mcaleer, Maryam Fouladi, David R Grosshans, Amol J Ghia, Jing Li, Wafik T Zaky, Murali M Chintagumpala, Joshua D Palmer, Susan L Mcgovern

Faculty, Staff and Student Publications

Purpose: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population.

Methods: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis.

Results: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival.

Conclusion: Age is a significant prognostic factor in WHO grade …

Screening Hydrogels For Antifibrotic Properties By Implanting Cellularly Barcoded Alginates In Mice And A Non-Human Primate, Sudip Mukherjee, Boram Kim, Lauren Y Cheng, Michael David Doerfert, Jiaming Li, Andrea Hernandez, Lily Liang, Maria I Jarvis, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Trisha Ray, Tanguy Terlier, Cody Fell, Ping Song, Roberto N Miranda, Jose Oberholzer, David Yu Zhang, Omid Veiseh

Faculty, Staff and Student Publications

Screening implantable biomaterials for antifibrotic properties is constrained by the need for in vivo testing. Here we show that the throughput of in vivo screening can be increased by cellularly barcoding a chemically modified combinatorial library of hydrogel formulations. The method involves the implantation of a mixture of alginate formulations, each barcoded with human umbilical vein endothelial cells from different donors, and the association of the identity and performance of each formulation by genotyping single nucleotide polymorphisms of the cells via next-generation sequencing. We used the method to screen 20 alginate formulations in a single mouse and 100 alginate formulations …

Severe Arsenic Poisoning Due To Ayurvedic Supplements, Jeremy Hardin, Justin Seltzer, Raymond Suhandynata, Benjamin Spiegel, Robin Silver, Diane Thomas, Henrik Galust, Nathan Friedman, Richard Clark, Jeremiah Momper

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Patients that are taking Ayurvedic supplements have an increased risk of heavy metal toxicity. Lead, arsenic, and mercury are frequently identified in these supplements and can cause clinically significant toxicity. Clinicians should screen patients routinely for use of non-pharmaceutical medications and supplements.

Addressing The Global Expertise Gap In Radiation Oncology: The Radiation Planning Assistant, Laurence Court, Ajay Aggarwal, Hester Burger, Carlos Cardenas, Christine Chung, Raphael Douglas, Monique Du Toit, David Jaffray, Anuja Jhingran, Michael Mejia, Raymond Mumme, Sikudhani Muya, Komeela Naidoo, Jerry Ndumbalo, Kelly Nealon, Tucker Netherton, Callistus Nguyen, Niki Olanrewaju, Jeannette Parkes, Willie Shaw, Christoph Trauernicht, Melody Xu, Jinzhong Yang, Lifei Zhang, Hannah Simonds, Beth M Beadle

Faculty, Staff and Student Publications

PURPOSE: Automation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).

DESIGN: In this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and …

Cisplatin Decreases Voluntary Wheel-Running Activity But Does Not Impair Food-Motivated Behavior In Mice, Kiersten S Scott, Brandon Chelette, Chinenye Chidomere, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less …

First-In-Human Study Of Oleclumab, A Potent, Selective Anti-Cd73 Monoclonal Antibody, Alone Or In Combination With Durvalumab In Patients With Advanced Solid Tumors, Johanna Bendell, Patricia Lorusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison, Minal Barve, Manik Amin, Jayesh Desai, Trisha Wise-Draper, Steven Eck, Yu Jiang, Anis A Khan, Yuling Wu, Philip Martin, Zachary A Cooper, Nairouz Elgeioushi, Nancy Mueller, Rakesh Kumar, Sandip Pravin Patel

Faculty, Staff and Student Publications

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy …

Emerging Signaling Regulation Of Sinoatrial Node Dysfunction, Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang

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PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND.

RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), …

Factors Affecting Treatment Adherence Among Leprosy Patients: Perceptions Of Healthcare Providers, Veincent Christian F Pepito, Arianna Maever Loreche, Rae Erica D Samontina, Sarah Jane A Abdon, David Norman L Fuentes, Ofelia P Saniel

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BACKGROUND: Treatment adherence is a vital aspect in the management of chronic diseases like leprosy; however, most studies on treatment adherence focus on patients. This study aims to examine the perceptions of healthcare providers on factors that can promote or prevent patients from adhering to treatment.

METHODS: We conducted three focus group discussions (FGDs) with healthcare providers who have at least one year experience in managing leprosy in three large leprosy case-holding hospitals in Metro Manila, Philippines. We audio-recorded, transcribed, translated the FGD proceedings, and analyzed the transcripts thematically to identify patient-intrinsic and patient-extrinsic enablers and barriers to treatment adherence …

Measuring Quality At The Surgeon Level, Elias A Chamely, Jonah J Stulberg

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Patients expect high-quality surgical care and increasingly are looking for ways to assess the quality of the surgeon they are seeing, but quality measurement is often more complicated than one might expect. Measurement of individual surgeon quality in a manner that allows for comparison among surgeons is particularly difficult. While the concept of measuring individual surgeon quality has a long history, technology now allows for new and innovative ways to measure and achieve surgical excellence. However, some recent efforts to make surgeon-level quality data publicly available have highlighted the challenges of this work. Through this chapter, the reader will be …

Transcriptional Profiling And Consensus Molecular Subtype Assignment To Understand Response And Resistance To Anti-Epidermal Growth Factor Receptor Therapy In Colorectal Cancer, Saikat Chowdhury, Ria Gupta, Joshua Millstein, Kangyu Lin, Valsala Haridas, Mohammad A Zeineddine, Christine Parseghian, Heinz-Josef Lenz, Scott Kopetz, John Paul Shen

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PURPOSE: Activating mutations in KRAS, NRAS, and BRAF are known to cause resistance to anti–epidermal growth factor receptor (EGFR) therapy; however, only approximately 40% of patients with colorectal cancer (CRC) with RASWT tumors respond to anti-EGFR treatment. We sought to discover novel biomarkers to predict response to anti-EGFR antibody treatment in CRC and to understand mechanisms of resistance to anti-EGFR therapy.

MATERIALS AND METHODS: Transcriptomic profiles from three clinical and two preclinical cohorts treated with cetuximab were used to assign consensus molecular subtypes (CMS) to each sample and correlated with outcomes.

RESULTS: Restricting to RASWT patients, …