Medical Sciences Commons^™

Oncology-Specific Radiation Dose And Image Noise Reference Levels In Adult Abdominal-Pelvic Ct, Moiz Ahmad, Xinming Liu, Ajaykumar C Morani, Dhakshinamoorthy Ganeshan, Marcus R Anderson, Ehsan Samei, Corey T Jensen

Faculty, Staff and Student Publications

OBJECTIVES: To provide our oncology-specific adult abdominal-pelvic CT reference levels for image noise and radiation dose from a high-volume, oncologic, tertiary referral center.

METHODS: The portal venous phase abdomen-pelvis acquisition was assessed for image noise and radiation dose in 13,320 contrast-enhanced CT examinations. Patient size (effective diameter) and radiation dose (CTDI

RESULTS: The noise reference level was 11.25 HU with a reference range of 10.25-12.25 HU. The dose reference level at a median effective diameter of 30.7 cm was 26.7 mGy with a reference range of 19.6-37.0 mGy. Dose increased with patient size; however, image noise remained approximately constant within …

Editorial: Big Data Analytics To Advance Stroke And Cerebrovascular Disease: A Tool To Bridge Translational And Clinical Research, Alexis Nétis Simpkins, Hari Kishan Reddy Indupuru, Sean Isaac Savitz

Faculty, Staff and Student Publications

No abstract provided.

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …

Effectiveness Without Efficacy: Cautionary Tale From A Landmark Breast Cancer Randomized Controlled Trial, Yu Shen, Jing Ning, Heather Y Lin, Simona F Shaitelman, Henry M Kuerer, Isabelle Bedrosian

Faculty, Staff and Student Publications

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment …

Targeting Mcl-1 Protein To Treat Cancer: Opportunities And Challenges, Shady I Tantawy, Natalia Timofeeva, Aloke Sarkar, Varsha Gandhi

Faculty, Staff and Student Publications

Evading apoptosis has been linked to tumor development and chemoresistance. One mechanism for this evasion is the overexpression of prosurvival B-cell lymphoma-2 (BCL-2) family proteins, which gives cancer cells a survival advantage. Mcl-1, a member of the BCL-2 family, is among the most frequently amplified genes in cancer. Targeting myeloid cell leukemia-1 (MCL-1) protein is a successful strategy to induce apoptosis and overcome tumor resistance to chemotherapy and targeted therapy. Various strategies to inhibit the antiapoptotic activity of MCL-1 protein, including transcription, translation, and the degradation of MCL-1 protein, have been tested. Neutralizing MCL-1's function by targeting its interactions …

Neurocognitive Correlates Of Cerebellar Volumetric Alterations In Youth With Pediatric Bipolar Spectrum Disorders And Bipolar Offspring, Kirti Saxena, Alessio Simonetti, Christopher D Verrico, Delfina Janiri, Marco Di Nicola, Antonello Catinari, Sherin Kurian, Johanna Saxena, Benson Mwangi, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: Emerging evidence points towards the involvement of the cerebellum in the processing of emotions and pathophysiology of mood disorders. However, cerebellar and related cognitive alterations in youth with pediatric bipolar disorder (PBD) and those at high risk to develop the disorder, such as bipolar offspring (BD-OFF) are not clearly defined.

OBJECTIVE: To investigate cerebellar gray and white matter volumes, cognition, and their relationship in youth with PBD and BD-OFF.

METHODS: Thirty youth (7 to 17 years, inclusive) with PBD, 30 BD-OFF and 40 healthy controls (HC) were recruited. Study participants underwent a computer-based cognitive battery assessing affective processing, executive …

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro

Faculty, Staff and Student Publications

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Brain-Derived Neurotrophic Factor In Fibromyalgia: A Systematic Review And Meta-Analysis Of Its Role As A Potential Biomarker, Amir Hossein Behnoush, Amirmohammad Khalaji, Shaghayegh Khanmohammadi, Parsa Alehossein, Behrad Saeedian, Parnian Shobeiri, Antonio L Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.

METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant …

Predictive Digital Twin For Optimizing Patient-Specific Radiotherapy Regimens Under Uncertainty In High-Grade Gliomas, Anirban Chaudhuri, Graham Pash, David A Hormuth, Guillermo Lorenzo, Michael Kapteyn, Chengyue Wu, Ernesto A B F Lima, Thomas E Yankeelov, Karen Willcox

Faculty, Staff and Student Publications

We develop a methodology to create data-driven predictive digital twins for optimal risk-aware clinical decision-making. We illustrate the methodology as an enabler for an anticipatory personalized treatment that accounts for uncertainties in the underlying tumor biology in high-grade gliomas, where heterogeneity in the response to standard-of-care (SOC) radiotherapy contributes to sub-optimal patient outcomes. The digital twin is initialized through prior distributions derived from population-level clinical data in the literature for a mechanistic model's parameters. Then the digital twin is personalized using Bayesian model calibration for assimilating patient-specific magnetic resonance imaging data. The calibrated digital twin is used to propose optimal …

The Proteasome: A Key Modulator Of Nervous System Function, Brain Aging, And Neurodegenerative Disease, Kanisa Davidson, Andrew M Pickering

Faculty, Staff and Student Publications

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays critical roles in nervous system processes. This includes maintenance of cellular homeostasis in neurons. It also includes roles in long-term potentiation via modulation of CREB signaling. The proteasome also possesses roles in promoting dendritic spine growth driven by proteasome localization to the dendritic spines in an NMDA/CaMKIIα dependent manner. Proteasome inhibition experiments in varied organisms has been shown to impact memory, consolidation, recollection and extinction. The proteasome has been further shown to impact circadian rhythm through modulation of …

Clinical Parameters Affecting Survival Outcomes In Patients With Low-Grade Serous Ovarian Carcinoma: An International Multicentre Analysis, Taymaa May, Marcus Bernardini, Stephanie Lheureux, Katja K H Aben, Elisa V Bandera, Matthias W Beckmann, Javier Benitez, Andrew Berchuck, Line Bjørge, Michael E Carney, Daniel W Cramer, Anna Defazio, Thilo Dörk, Diana M Eccles, Michael Friedlander, María Jose García, Ellen L Goode, Alexander Hein, Claus K Høgdall, Allan Jensen, Sharon Johnatty, Catherine J Kennedy, Lambertus A Kiemeney, Susanne K Kjær, Jolanta Kupryjańczyk, Keitaro Matsuo, Valerie Mcguire, Francesmary Modugno, Lisa E Paddock, Tanja Pejovic, Catherine M Phelan, Marjorie J Riggan, Cristina Rodriguez-Antona, Joseph H Rothstein, Weiva Sieh, Honglin Song, Kathryn L Terry, Anne M Van Altena, Adriaan Vanderstichele, Ignace Vergote, Liv Cecilie Vestrheim Thomsen, Penelope M Webb, Nicolas Wentzensen, Lynne R Wilkens, Argyrios Ziogas, Haiyan Jiang, Alicia Tone, Ovarian Cancer Association And The Australian Ovarian Cancer Study Group

Faculty, Staff and Student Publications

BACKGROUND: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.

METHODS: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves.

RESULTS: Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of …

Radiographic Response To Neoadjuvant Therapy In Pleural Mesothelioma Should Serve As A Guide For Patient Selection For Cytoreductive Operations, Nathaniel Deboever, Nicolas Zhou, Daniel J Mcgrail, Katarzyna Tomczak, Jacqueline L Oliva, Hope A Feldman, Edwin Parra, Jianjun Zhang, Percy P Lee, Mara B Antonoff, Wayne L Hofstetter, Reza J Mehran, Ravi Rajaram, David C Rice, Jack A Roth, Stephen S Swisher, Ara A Vaporciyan, Mehmet Altan, Annikka Weissferdt, Anne S Tsao, Cara L Haymaker, Boris Sepesi

Faculty, Staff and Student Publications

BACKGROUND: Malignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).

METHODS: Patients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to …

The Rising Tide Of Revisional Surgery: Tracking Changes In Index Cases Among Bariatric-Accredited Fellowships, Lincoln N Strickland, Erika Y Faraoni, Wei Ruan, Xiaoyi Yuan, Holger K Eltzschig, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Student Publications

Objective: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

Research design and methods: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Neuroanatomical Correlates Of The Late Positive Potential In Youth With Pediatric Bipolar Disorder, Alessio Simonetti, Marijn Lijffijt, Sherin Kurian, Johanna Saxena, Delfina Janiri, Marianna Mazza, Giulio Carriero, Lorenzo Moccia, Benson Mwangi, Alan C Swann, Jair C Soares

Faculty, Staff and Student Publications

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified.

OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD.

METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. …

Subcortical Functional Connectivity And Its Association With Walking Performance Following Deployment Related Mild Tbi, Mary R Newsome, Sarah L Martindale, Nicholas Davenport, Emily L Dennis, Marlene Diaz, Carrie Esopenko, Cooper Hodges, George R Jackson, Qisheng Liu, Kimbra Kenney, Andrew R Mayer, Jared A Rowland, Randall S Scheibel, Joel L Steinberg, Brian A Taylor, David F Tate, J Kent Werner, William C Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

INTRODUCTION: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred.

METHODS: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, …

Accelerating Artificial Intelligence: How Federated Learning Can Protect Privacy, Facilitate Collaboration, And Improve Outcomes, Malhar Patel, Ittai Dayan, Elliot K Fishman, Mona Flores, Fiona J Gilbert, Michal Guindy, Eugene J Koay, Michael Rosenthal, Holger R Roth, Marius G Linguraru

Faculty, Staff and Student Publications

Cross-institution collaborations are constrained by data-sharing challenges. These challenges hamper innovation, particularly in artificial intelligence, where models require diverse data to ensure strong performance. Federated learning (FL) solves data-sharing challenges. In typical collaborations, data is sent to a central repository where models are trained. With FL, models are sent to participating sites, trained locally, and model weights aggregated to create a master model with improved performance. At the 2021 Radiology Society of North America's (RSNA) conference, a panel was conducted titled "Accelerating AI: How Federated Learning Can Protect Privacy, Facilitate Collaboration and Improve Outcomes." Two groups shared insights: researchers from …

Mechanisms Of Resistance To Egfr-Targeted Therapies In Colorectal Cancer: More Than Just Genetics, Christine Parseghian, Madhulika Eluri, Scott Kopetz, Kanwal Raghav

Faculty, Staff and Student Publications

The development of acquired resistance to anti-EGFR therapies remains poorly understood, with most research to date exploring, and trying to overcome, various genomic mechanisms of resistance. However, recent work supports a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with anti-EGFR therapy in the first-line setting, with a greater predominance of acquired MAPK mutations after single-agent anti-EGFR therapy in the later-line setting. The proposed model has implications for prospective studies evaluating anti-EGFR rechallenge strategies guided by acquired MAPK mutations and highlights the need to address transcriptional mechanisms of resistance.

Case Report: Responses To The Combination Of Gemcitabine With Sirolimus In Two Patients With Tsc-Mutated Sarcomas, Elise F Nassif, Cissimol P Joseph, Rossana Lazcano, Jocelyn T Joseph, Prapassorn Thirasastr, Alexander J Lazar, Neeta Somaiah

Faculty, Staff and Student Publications

TSC-mutated sarcomas are rare molecular and histologic types of sarcoma. Due to the presence of their specific oncogenic driver mutation, these sarcomas are particularly sensitive to mTOR inhibitors. Recently, nab-sirolimus, an albumin-bound mTOR inhibitor, was approved by the Food and Drug Administration (FDA) for PEComas, which harbor a TSC mutation, and this drug remains the only FDA-approved systemic treatment for these tumors. We report on two cases of patients with TSC-mutated sarcomas who experienced significant responses to the combination of gemcitabine and sirolimus, after progression on prior gemcitabine-based chemotherapy and single agent mTOR inhibition with nab-sirolimus. …

Predictive Power Of Deep-Learning Segmentation Based Prognostication Model In Non-Small Cell Lung Cancer, Jordan C Gainey, Yusen He, Robert Zhu, Stephen S Baek, Xiaodong Wu, John M Buatti, Bryan G Allen, Brian J Smith, Yusung Kim

Faculty, Staff and Student Publications

Purpose: The study aims to create a model to predict survival outcomes for non-small cell lung cancer (NSCLC) after treatment with stereotactic body radiotherapy (SBRT) using deep-learning segmentation based prognostication (DESEP).

Methods: The DESEP model was trained using imaging from 108 patients with NSCLC with various clinical stages and treatment histories. The model generated predictions based on unsupervised features learned by a deep-segmentation network from computed tomography imaging to categorize patients into high and low risk groups for overall survival (DESEP-predicted-OS), disease specific survival (DESEP-predicted-DSS), and local progression free survival (DESEP-predicted-LPFS). Serial assessments were also performed using auto-segmentation based volumetric …

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …

Il-8 Produced Via Bidirectional Communication Between Prostate Cancer And M2 Macrophages As A Potential Diagnostic And Prognostic Biomarker, Huihui Fan, Zheng Tang, Yaling Tian, Qingsong Lv, Fangyin Zeng

Faculty, Staff and Student Publications

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer.

METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Pepsim: T-Cell Cross-Reactivity Prediction Via Comparison Of Peptide Sequence And Peptide-Hla Structure, Sarah Hall-Swan, Jared Slone, Mauricio M Rigo, Dinler A Antunes, Gregory Lizée, Lydia E Kavraki

Faculty, Staff and Student Publications

INTRODUCTION: Peptide-HLA class I (pHLA) complexes on the surface of tumor cells can be targeted by cytotoxic T-cells to eliminate tumors, and this is one of the bases for T-cell-based immunotherapies. However, there exist cases where therapeutic T-cells directed towards tumor pHLA complexes may also recognize pHLAs from healthy normal cells. The process where the same T-cell clone recognizes more than one pHLA is referred to as T-cell cross-reactivity and this process is driven mainly by features that make pHLAs similar to each other. T-cell cross-reactivity prediction is critical for designing T-cell-based cancer immunotherapies that are both effective and safe. …

Anti-Inflammatory Effects Of Vagus Nerve Stimulation In Pediatric Patients With Epilepsy, Supender Kaur, Nathan R Selden, Alejandro Aballay

Faculty, Staff and Student Publications

INTRODUCTION: The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.

METHODS: Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression …

Effect Of Nodule Size And Stiffness On Phonation Threshold And Collision Pressures In A Synthetic Hemilaryngeal Vocal Fold Model, Mohsen Motie-Shirazi, Matías Zañartu, Sean D Peterson, Daryush D Mehta, Robert E Hillman, Byron D Erath

Faculty, Staff and Student Publications

Synthetic vocal fold (VF) replicas were used to explore the role of nodule size and stiffness on kinematic, aerodynamic, and acoustic measures of voiced speech production. Emphasis was placed on determining how changes in collision pressure may contribute to the development of phonotrauma. This was performed by adding spherical beads with different sizes and moduli of elasticity at the middle of the medial surface of synthetic silicone VF models, representing nodules of varying size and stiffness. The VF models were incorporated into a hemilaryngeal flow facility. For each case, self-sustained oscillations were investigated at the phonation threshold pressure. It was …

Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson

Faculty, Staff and Student Publications

Deep learning methods for image segmentation and contouring are gaining prominence as an automated approach for delineating anatomical structures in medical images during radiation treatment planning. These contours are used to guide radiotherapy treatment planning, so it is important that contouring errors are flagged before they are used for planning. This creates a need for effective quality assurance methods to enable the clinical use of automated contours in radiotherapy. We propose a novel method for contour quality assurance that requires only shape features, making it independent of the platform used to obtain the images. Our method uses a random forest …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M Willems, Natasha H J Ng, Juan Fernandez, Rebecca S Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Xueling Sim, Hanieh Yaghootkar, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Niels Grarup, Ruifang Li-Gao, Tibor V Varga, Jennifer L Asimit, Shuang Feng, Rona J Strawbridge, Erica L Kleinbrink, Tarunveer S Ahluwalia, Ping An, Emil V Appel, Dan E Arking, Juha Auvinen, Lawrence F Bielak, Nathan A Bihlmeyer, Jette Bork-Jensen, Jennifer A Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Anne U Jackson, Johanna Jakobsdottir, Marjo-Riitta Järvelin, Richard A Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Man Li, Yingchang Lu, Jian'an Luan, Alisa K Manning, Jonathan Marten, Karina Meidtner, Dennis O Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M Rice, Serena Sanna, Albert Vernon Smith, Jennifer A Smith, Lorraine Southam, Heather M Stringham, Vinicius Tragante, Sander W Van Der Laan, Helen R Warren, Jie Yao, Andrianos M Yiorkas, Weihua Zhang, Wei Zhao, Mariaelisa Graff, Heather M Highland, Anne E Justice, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W Asselbergs, Lori L Bonnycastle, Michiel L Bots, Ivan Brandslund, Ji Chen, John Danesh, Renée De Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, Epic-Interact Consortium, Aliki-Eleni Farmaki, Jessica D Faul, Paul W Franks, Steve Franks, Andreas Fritsche, Anette P Gjesing, Mark O Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B Harris, Karl-Heinz Herzig, Marie-France Hivert, Torben Jørgensen, Marit E Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L R Kardia, Leena Kinnunen, Heikki A Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A Lange, Lenore J Launer, Aaron Leong, Jaana Lindström, Jocelyn E Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A Nalls, Matthew Neville, James S Pankow, Alison Pattie, Eva R B Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D Taylor, Betina H Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group;, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P Bottinger, Mark J Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Francis S Collins, Josef Coresh, Francesco Cucca, Gert J De Borst, Ian J Deary, George Dedoussis, Panos Deloukas, Hester M Den Ruijter, Josée Dupuis, Michele K Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Torben Hansen, Andrew T Hattersley, Caroline Hayward, Joel N Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J F Loos, Patrick E Macdonald, Karen L Mohlke, Andrew D Morris, Patricia B Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A Peyser, Ozren Polasek, David Porteous, Michael A Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M Starr, Michael Stumvoll, Cornelia M Van Duijn, Mark Walker, Nick J Wareham, David R Weir, James G Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B Zonderman, Jerome I Rotter, Andrew P Morris, Michael Boehnke, Jose C Florez, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Robert A Scott, Anna L Gloyn, Inês Barroso

Faculty, Staff and Student Publications

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network …