Medicine and Health Sciences Commons^™

First-In-Human Phase I Study Of The Ox40 Agonist Gsk3174998 With Or Without Pembrolizumab In Patients With Selected Advanced Solid Tumors (Engage-1), Sophie Postel-Vinay, Vincent K Lam, Willeke Ros, Todd M Bauer, Aaron R Hansen, Daniel C Cho, F Stephen Hodi, Jan H M Schellens, Jennifer K Litton, Sandrine Aspeslagh, Karen A Autio, Frans L Opdam, Meredith Mckean, Neeta Somaiah, Stephane Champiat, Mehmet Altan, Anna Spreafico, Osama Rahma, Elaine M Paul, Christoph M Ahlers, Helen Zhou, Herbert Struemper, Shelby A Gorman, Maura Watmuff, Kaitlin M Yablonski, Niranjan Yanamandra, Michael J Chisamore, Emmett V Schmidt, Axel Hoos, Aurelien Marabelle, Jeffrey S Weber, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors.

METHODS: GSK3174998 (0.003-10 mg/kg) ± pembrolizumab (200 mg) was administered intravenously every 3 weeks using a continuous reassessment method for dose escalation. Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics, immunogenicity, pharmacodynamics, and clinical activity.

RESULTS: 138 patients were enrolled (45 (P1) and 96 (P2, including 3 crossovers)). Treatment-related adverse events occurred in 51% (P1) and 64% (P2) of patients, fatigue being the most …

Vidutolimod In Combination With Atezolizumab With And Without Radiation Therapy In Patients With Programmed Cell Death Protein 1 Or Programmed Death-Ligand 1 Blockade-Resistant Advanced Nsclc, Marcelo V Negrao, Vassiliki A Papadimitrakopoulou, Andrew C Price, Alda L Tam, Muhammad Furqan, Sandeep T Laroia, Erminia Massarelli, Jose Pacheco, John V Heymach, Anne S Tsao, Gary V Walker, Lalit Vora, David Mauro, Heather Kelley, James E Wooldridge, Arthur M Krieg, Jiaxin Niu

Faculty, Staff and Student Publications

INTRODUCTION: Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC.

METHODS: Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1.

RESULTS: Between March 28, 2018, …

Persistent Nociceptor Hyperactivity As A Painful Evolutionary Adaptation, Edgar T Walters, Robyn J Crook, G Gregory Neely, Theodore J Price, Ewan St John Smith

Faculty, Staff and Student Publications

Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Novel Genetic Regulators Of Fibrinogen Synthesis Identified By An In Vitro Experimental Platform, Dre'von A Dobson, Lori A Holle, Feng-Chang Lin, Jennifer E Huffman, James P Luyendyk, Matthew J Flick, Nicholas L Smith, Paul S De Vries, Alanna C Morrison, Alisa S Wolberg

Faculty, Staff and Student Publications

BACKGROUND: Fibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic and atherosclerotic diseases. Previous studies aimed to better understand the (patho) physiological actions of fibrinogen by characterizing the genomic contribution to circulating fibrinogen levels.

OBJECTIVES: Establish an in vitro approach to define functional roles between genes within these loci and fibrinogen synthesis.

METHODS: Candidate genes were selected on the basis of their proximity to genetic variants associated with fibrinogen levels and expression in hepatocytes and HepG2 cells. HepG2 cells were transfected with small interfering RNAs targeting …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G Izquierdo, Jing Chen, Richard Packer, Robert J Hall, Anna L Guyatt, Chiara Batini, Rebecca J Thompson, Chandan Pavuluri, Vidhi Malik, Brian D Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Alfred Pozarickij, Kuang Lin, Iona Y Millwood, Zhengming Chen, Liming Li, China Kadoorie Biobank Collaborative Group, Sara R A Wijnant, Lies Lahousse, Guy Brusselle, Andre G Uitterlinden, Ani Manichaikul, Elizabeth C Oelsner, Stephen S Rich, R Graham Barr, Shona M Kerr, Veronique Vitart, Michael R Brown, Matthias Wielscher, Medea Imboden, Ayoung Jeong, Traci M Bartz, Sina A Gharib, Claudia Flexeder, Stefan Karrasch, Christian Gieger, Annette Peters, Beate Stubbe, Xiaowei Hu, Victor E Ortega, Deborah A Meyers, Eugene R Bleecker, Stacey B Gabriel, Namrata Gupta, Albert Vernon Smith, Jian'an Luan, Jing-Hua Zhao, Ailin F Hansen, Arnulf Langhammer, Cristen Willer, Laxmi Bhatta, David Porteous, Blair H Smith, Archie Campbell, Tamar Sofer, Jiwon Lee, Martha L Daviglus, Bing Yu, Elise Lim, Hanfei Xu, George T O'Connor, Gaurav Thareja, Omar M E Albagha, Qatar Genome Program Research (Qgpr) Consortium, Karsten Suhre, Raquel Granell, Tariq O Faquih, Pieter S Hiemstra, Annelies M Slats, Benjamin H Mullin, Jennie Hui, Alan James, John Beilby, Karina Patasova, Pirro Hysi, Jukka T Koskela, Annah B Wyss, Jianping Jin, Sinjini Sikdar, Mikyeong Lee, Sebastian May-Wilson, Nicola Pirastu, Katherine A Kentistou, Peter K Joshi, Paul R H J Timmers, Alexander T Williams, Robert C Free, Xueyang Wang, John L Morrison, Frank D Gilliland, Zhanghua Chen, Carol A Wang, Rachel E Foong, Sarah E Harris, Adele Taylor, Paul Redmond, James P Cook, Anubha Mahajan, Lars Lind, Teemu Palviainen, Terho Lehtimäki, Olli T Raitakari, Jaakko Kaprio, Taina Rantanen, Kirsi H Pietiläinen, Simon R Cox, Craig E Pennell, Graham L Hall, W James Gauderman, Chris Brightling, James F Wilson, Tuula Vasankari, Tarja Laitinen, Veikko Salomaa, Dennis O Mook-Kanamori, Nicholas J Timpson, Eleftheria Zeggini, Josée Dupuis, Caroline Hayward, Ben Brumpton, Claudia Langenberg, Stefan Weiss, Georg Homuth, Carsten Oliver Schmidt, Nicole Probst-Hensch, Marjo-Riitta Jarvelin, Alanna C Morrison, Ozren Polasek, Igor Rudan, Joo-Hyeon Lee, Ian Sayers, Emma L Rawlins, Frank Dudbridge, Edwin K Silverman, David P Strachan, Robin G Walters, Andrew P Morris, Stephanie J London, Michael H Cho, Louise V Wain, Ian P Hall, Martin D Tobin

Faculty, Staff and Student Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

Causes Of Clonal Hematopoiesis: A Review, Lijin Joo, Catherine C Bradley, Steven H Lin, Paul A Scheet, Kevin T Nead

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Clonal hematopoiesis (CH) is an age-dependent process detectable using advanced sequencing technologies and is associated with multiple adverse health outcomes including cardiovascular disease and cancer. The purpose of this review is to summarize known causes of CH mutations and to identify key areas and considerations for future research on CH.

RECENT FINDINGS: Studies have identified multiple potential causes of CH mutations including smoking, cancer therapies, cardiometabolic disease, inflammation, and germline risk factors. Additionally, large-scale studies have facilitated the identification of gene-specific effects of CH mutation risk factors that may have unique downstream health implications. For example, cancer …

Expansion Of The Genotypic And Phenotypic Spectrum Of Ctcf-Related Disorder Guides Clinical Management: 43 New Subjects And A Comprehensive Literature Review, Hannah Gabriela Valverde De Morales, Hsiao-Lin V Wang, Kathryn Garber, Xiaodong Cheng, Victor G Corces, Hong Li

Faculty, Staff and Student Publications

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed. Here, we examined the clinical features, including facial profiles, and genotypic spectrum of 107 subjects with identified CTCF variants, including 43 new and 64 previously described subjects. Among the 43 new subjects, 23 novel variants were reported. The cardinal clinical features in subjects with …

Mitochondrial Structure And Function Adaptation In Residual Triple Negative Breast Cancer Cells Surviving Chemotherapy Treatment, Mokryun L Baek, Junegoo Lee, Katherine E Pendleton, Mariah J Berner, Emily B Goff, Lin Tan, Sara A Martinez, Iqbal Mahmud, Tao Wang, Matthew D Meyer, Bora Lim, James P Barrish, Weston Porter, Philip L Lorenzi, Gloria V Echeverria

Faculty, Staff and Student Publications

Neoadjuvant chemotherapy (NACT) used for triple negative breast cancer (TNBC) eradicates tumors in ~45% of patients. Unfortunately, TNBC patients with substantial residual cancer burden have poor metastasis free and overall survival rates. We previously demonstrated mitochondrial oxidative phosphorylation (OXPHOS) was elevated and was a unique therapeutic dependency of residual TNBC cells surviving NACT. We sought to investigate the mechanism underlying this enhanced reliance on mitochondrial metabolism. Mitochondria are morphologically plastic organelles that cycle between fission and fusion to maintain mitochondrial integrity and metabolic homeostasis. The functional impact of mitochondrial structure on metabolic output is highly context dependent. Several chemotherapy agents …

Mew Network Self-Management Program Characteristics And Lessons Learned Through The Re-Aim Framework, Cam Escoffery, Archna Patel, Jerik Leung, Molly Anderson, Robin Mcgee, Martha Sajatovic, Erica K Johnson, Barbara Jobst, Elaine T Kiriakopoulos, Ross Shegog, Robert Fraser, Rakale C Quarells

Faculty, Staff and Student Publications

RATIONALE: The promotion of evidence-based self-management support for people living with chronic conditions such as epilepsy is a public health priority. Epilepsy self-management encompasses three general areas: (1) treatment management, (2) seizure management, and (3) lifestyle management. Interventions focusing on self-management have increased quality of life and adherence to treatment. This study assesses and synthesizes the Managing Epilepsy Well Network (MEWN) program implementation experiences using the RE-AIM framework. This research informs the quality and rigor of MEWN program dissemination and implementation efforts to assess whether these programs are being implemented and their scalability.

METHODS: The study data were derived from …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

Alzheimer's Disease Genetic Risk, Cognition, And Brain Aging In Midlife, Willa D Brenowitz, Myriam Fornage, Lenore J Launer, Mohamad Habes, Christos Davatzikos, Kristine Yaffe

Faculty, Staff and Student Publications

We examined associations of an AD genetic risk score (AD-GRS) and midlife cognitive and neuroimaging outcomes in 1,252 middle-aged participants (311 with brain MRI). A higher AD-GRS based on 25 previously identified loci (excluding APOE) was associated with worse Montreal Cognitive Assessment (−0.14 SD[95% CI:−0.26,−0.02]), older machine learning predicted brain age (2.35 years[95%CI:0.01,4.69]), and white matter hyperintensity volume (0.35 SD [95% CI:0.00,0.71), but not with a composite cognitive outcome, total brain, or hippocampal volume. APOE ε4 allele was not associated with any outcomes. AD risk genes beyond APOE may contribute to subclinical differences in cognition and brain health in …

A Means Of Codifying Safety Cross-Training Knowledge Expectations For Biosafety Professionals, Robert J Emery, Scott J Patlovich, Kristin G King, Janelle Rios

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INTRODUCTION: The health and safety issues encountered by biosafety professionals in the daily conduct of their work is rarely limited solely to potentially infectious pathogens. A basic understanding of the other types of hazards inherent to laboratories is necessary. As such, management of the health and safety program at an academic health institution sought to ensure crosscutting competency for its technical staff, including staff members within the biosafety program.

METHODS: Using a focus group approach, a team of safety professionals from a variety of specialties developed a list of 50 basic health and safety items that any safety specialist should …

The Risk Of Sars-Cov-2 Omicron Variant Emergence In Low And Middle-Income Countries (Lmics), Kaiming Bi, Jose Luis Herrera-Diestra, Yuan Bai, Zhanwei Du, Lin Wang, Graham Gibson, Maureen Johnson-Leon, Spencer J Fox, Lauren Ancel Meyers

Faculty, Staff and Student Publications

We estimated the probability of undetected emergence of the SARS-CoV-2 Omicron variant in 25 low and middle-income countries (LMICs) prior to December 5, 2021. In nine countries, the risk exceeds 50 %; in Turkey, Pakistan and the Philippines, it exceeds 99 %. Risks are generally lower in the Americas than Europe or Asia.

The Role Of Gender Inequality And Health Expenditure On The Coverage Of Demand For Family Planning Satisfied By Modern Contraceptives: A Multilevel Analysis Of Cross-Sectional Studies In 14 Lac Countries, Laísa Rodrigues Moreira, Cauane Blumenberg, Beatriz Elena Caicedo Velasquez, Fernanda Ewerling, Alejandra Balandrán, Luis Paulo Vidaletti, Andrea Ramirez Varela, Franciele Hellwig, Rodolfo Gomez Ponce De Leon, Aluisio J D Barros, Mariangela Freitas Silveira, Fernando C Wehrmeister

Faculty, Staff and Student Publications

BACKGROUND: Despite international efforts to improve reproductive health indicators, little attention is paid to the contributions of contextual factors to modern contraceptive coverage, especially in the Latin America and the Caribbean (LAC) region. This study aimed to identify the association between country-level Gender Inequality and Health Expenditure with demand for family planning satisfied by modern contraceptive methods (DFPSm) in Latin American sexually active women.

METHODS: Our analyses included data from the most recent (post-2010) Demographic and Health Survey or Multiple Indicator Cluster Survey from 14 LAC countries. Descriptive analyses and multilevel logistic regressions were performed. Six individual-level factors were included. …

Delphi Initiative For Early-Onset Colorectal Cancer (Direct) International Management Guidelines, Giulia Martina Cavestro, Alessandro Mannucci, Francesc Balaguer, Heather Hampel, Sonia S Kupfer, Alessandro Repici, Andrea Sartore-Bianchi, Toni T Seppälä, Vincenzo Valentini, Clement Richard Boland, Randall E Brand, Tineke E Buffart, Carol A Burke, Riccardo Caccialanza, Renato Cannizzaro, Stefano Cascinu, Andrea Cercek, Emma J Crosbie, Silvio Danese, Evelien Dekker, Maria Daca-Alvarez, Francesco Deni, Mev Dominguez-Valentin, Cathy Eng, Ajay Goel, Josè G Guillem, Britt B S L Houwen, Charles Kahi, Matthew F Kalady, Fay Kastrinos, Florian Kühn, Luigi Laghi, Andrew Latchford, David Liska, Patrick Lynch, Alberto Malesci, Gianluca Mauri, Elisa Meldolesi, Pål Møller, Kevin J Monahan, Gabriela Möslein, Caitlin C Murphy, Karlijn Nass, Kimmie Ng, Cristina Oliani, Enrico Papaleo, Swati G Patel, Marta Puzzono, Andrea Remo, Luigi Ricciardiello, Carla Ida Ripamonti, Salvatore Siena, Satish K Singh, Zsofia K Stadler, Peter P Stanich, Sapna Syngal, Stefano Turi, Emanuele Damiano Urso, Laura Valle, Valeria Stella Vanni, Eduardo Vilar, Marco Vitellaro, Yi-Qian Nancy You, Matthew B Yurgelun, Raffaella Alessia Zuppardo, Elena M Stoffel, Associazione Italiana Familiarità Ereditarietà Tumori, Collaborative Group Of The Americas On Inherited Gastrointestinal Cancer, European Hereditary Tumour Group, And The International Society For Gastrointestinal Hereditary Tumours

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BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.

METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.

RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that …

Use Of Contrast Media During Ct-Guided Thermal Ablation Of Colorectal Liver Metastasis For Procedure Planning Is Associated With Improved Immediate Outcomes, Iwan Paolucci, Yuan-Mao Lin, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.

MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used …

Metabolomic Markers Of Ultra-Processed Food And Incident Ckd, Donghan Su, Jingsha Chen, Shutong Du, Hyunju Kim, Bing Yu, Kari E Wong, Eric Boerwinkle, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD.

METHODS: We used data from 3751 Black and White men and women (aged 45-64 years) in …

Sustainability Considerations For Consumables Used In Microbiological And Biomedical Laboratories, Autumn Cerda, Robert Emery, Scott Patlovich

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Introduction: The 6th edition of the Biosafety in Microbiological and Biomedical Laboratories includes Appendix L on sustainability that describes a series of considerations for biocontainment facilities. But many biosafety practitioners may not be familiar with sustainability options that are available, feasible, and safe for laboratory settings as training in this realm is not common.

Methods: With a particular focus on consumable products used in containment laboratory operations, a comparative assessment was made regarding sustainability activities employed in the healthcare setting, where significant advances have been achieved.

Results: Table 1 has been created that describes various consumables that result in waste …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

Objective: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

Summary of background data: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

Methods: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Recent Advances In Centrifugal Spinning And Their Applications In Tissue Engineering, Shaik Merkatur Hakim Marjuban, Musfira Rahman, Syeda Sharmin Duza, Mohammad Boshir Ahmed, Dinesh K Patel, Md Saifur Rahman, Karen Lozano

Faculty, Staff and Student Publications

Over the last decade, researchers have investigated the potential of nano and microfiber scaffolds to promote wound healing, tissue regeneration, and skin protection. The centrifugal spinning technique is favored over others due to its relatively straightforward mechanism for producing large quantities of fiber. Many polymeric materials have yet to be investigated in search of those with multifunctional properties that would make them attractive in tissue applications. This literature presents the fundamental process of fiber generation, and the effects of fabrication parameters (machine, solution) on the morphologies such as fiber diameter, distribution, alignment, porous features, and mechanical properties. Additionally, a brief …

Efficacy Of Delta Plate In Condylar Fracture: A Case Series With Review, Aniket Sarkar, Lahari Banerjee, Samiran Ghosh

Faculty, Staff and Student Publications

Open reduction and internal fixation (ORIF) of mandibular condylar fracture with a three dimensional stabilization has been a controversial topic in oral and maxillofacial surgery. Miniplates and many 3D plates have been used till now for fixation of condylar fracture and delta plate is one of them. Present literature has less evidence about which one is superior over another. We have tried to evaluate the clinical performance of the delta miniplate in this study. A total of 10 patients presenting mandibular condylar fracture were treated by ORIF using delta miniplate. Dimensional details were measured of 10 dry human mandibles. At …

Development Of Quality Measures To Assess Tooth Decay Outcomes From Electronic Health Record Data, Ryan G Brandon, Suhasini Bangar, Alfa Yansane, Ana Neumann, Joanna M Mullins, Elsbeth Kalenderian, Muhammad F Walji, Joel M White

Faculty, Staff and Student Publications

Objectives: To develop outcomes of care quality measures derived from the dental electronic health record (EHR) to assess the occurrence and timely treatment of tooth decay.

Methods: Quality measures were developed to assess whether decay was treated within 6 months and if new decay occurred in patients seen. Using EHR-derived data of the state of each tooth surface, algorithms compared the patient's teeth at different dates to determine if decay was treated or new decay had occurred. Manual chart reviews were conducted at three sites to validate the measures. The measures were implemented and scores were calculated for three sites …

Epigenome-Wide Association Study Reveals Cpg Sites Associated With Thyroid Function And Regulatory Effects On Klf9, Antoine Weihs, Layal Chaker, Tiphaine C Martin, Kim V E Braun, Purdey J Campbell, Simon R Cox, Myriam Fornage, Christian Gieger, Hans J Grabe, Harald Grallert, Sarah E Harris, Brigitte Kühnel, Riccardo E Marioni, Nicholas G Martin, Daniel L Mccartney, Allan F Mcrae, Christa Meisinger, Joyce B J Van Meurs, Jana Nano, Matthias Nauck, Annette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana Van Heemst, Eline P Slagboom, Brenton R Swenson, Adrienne Tin, Pei-Chien Tsai, Andre Uitterlinden, W Edward Visser, Henry Völzke, Melanie Waldenberger, John P Walsh, Anna Köttgen, Scott G Wilson, Robin P Peeters, Jordana T Bell, Marco Medici, Alexander Teumer

Faculty, Staff and Student Publications

Background:

Thyroid hormones play a key role in differentiation and metabolism and are known regulators of gene expression through both genomic and epigenetic processes including DNA methylation. The aim of this study was to examine associations between thyroid hormones and DNA methylation.

Methods:

We carried out a fixed-effect meta-analysis of epigenome-wide association study (EWAS) of blood DNA methylation sites from 8 cohorts from the ThyroidOmics Consortium, incorporating up to 7073 participants of both European and African ancestry, implementing a discovery and replication stage. Statistical analyses were conducted using normalized beta CpG values as dependent and log-transformed thyrotropin (TSH), free thyroxine, …

Global Epidemiology And Clinical Outcomes Of Carbapenem-Resistant Pseudomonas Aeruginosa And Associated Carbapenemases (Pop): A Prospective Cohort Study, Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake M Hanson, Eric Cober, Erica Herc, Thamer Alenazi, Keith S Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha S Kanj, Zhengyin Liu, Jose M Oñate, Robert A Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra L Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian M Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin E Stryjewski, Jose M Munita, David L Paterson, Scott Evans, Carol Hill, Keri Baum, Robert A Bonomo, Barry N Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, Yohei Doi, David Van Duin, Michael J Satlin

Faculty, Staff and Student Publications

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.

Methods: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day …

Customizable Landmark-Based Field Aperture Design For Automated Whole-Brain Radiotherapy Treatment Planning, Yao Xiao, Carlos Cardenas, Dong Joo Rhee, Tucker Netherton, Lifei Zhang, Callistus Nguyen, Raphael Douglas, Raymond Mumme, Stephen Skett, Tina Patel, Chris Trauernicht, Caroline Chung, Hannah Simonds, Ajay Aggarwal, Laurence Court

Faculty, Staff and Student Publications

Purpose: To develop and evaluate an automated whole-brain radiotherapy (WBRT) treatment planning pipeline with a deep learning-based auto-contouring and customizable landmark-based field aperture design.

Methods: The pipeline consisted of the following steps: (1) Auto-contour normal structures on computed tomography scans and digitally reconstructed radiographs using deep learning techniques, (2) locate the landmark structures using the beam's-eye-view, (3) generate field apertures based on eight different landmark rules addressing different clinical purposes and physician preferences. Two parallel approaches for generating field apertures were developed for quality control. The performance of the generated field shapes and dose distributions were compared with the original …

Clinical Outcomes Of Combined Cervical And Transthoracic Surgical Approaches In Patients With Advanced Thyroid Cancer, Jared A Shenson, Mark E Zafereo, Mark Lee, Kevin J Contrera, Lei Feng, Mongkol Boonsripitayanon, Neil Gross, Ryan Goepfert, Anastasios Maniakas, Jennifer Rui Wang, Libby Grubbs, Ara Vaporciyan, Wayne Hofstetter, Stephen Swisher, Reza Mehran, David Rice, Boris Sepesi, Mara Antonoff, Maria Cabanillas, Naifa Busaidy, Ramona Dadu, Natalie L Silver

Faculty, Staff and Student Publications

Background: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.

Methods: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015.

Results: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and …

Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth And Metabolic Reprogramming Leading To Chemoresistance, Sumeet Solanki, Katherine Sanchez, Varun Ponnusamy, Vasudha Kota, Hannah N Bell, Chun-Seok Cho, Allison H Kowalsky, Michael Green, Jun Hee Lee, Yatrik M Shah

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear.

METHODS: Human colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic …

An Extension Of Estimating Equations To Model Longitudinal Medical Cost Trajectory With Medicare Claims Data Linked To Seer Cancer Registry, Shikun Wang, Jing Ning, Ying Xu, Ya-Chen Tina Shih, Y U Shen, Liang Li

Faculty, Staff and Student Publications

Insurance claims data is an increasingly important health policy research resource, given its longitudinal assessment of cancer care clinical outcomes. Population-level information on medical cost trajectory from disease diagnosis to terminal events, such as death, specifically interests policy makers. Estimating the mean cost trajectory has statistical challenges. The shape of the trajectory is usually highly nonlinear with varying durations, depending on the diagnosis-to-death population time distribution. The terminal event may be right censored, resulting in missing subsequent costs. Medical costs often have skewed distributions with zero-inflation and heteroscedasticity, which may not fit well with the commonly used parametric family of …

Adding The X-Ray Bragg Reflection Physical Process In Crystal To The Geant4 Monte Carlo Simulation Toolkit, Part I: Reflection From A Crystal Slab, Fada Guan, Makoto Asai, Dirk A Bartkoski, Michael Kleckner, Ze'ev Harel, Mohammad Salehpour

Faculty, Staff and Student Publications

X-ray diffraction from a solid crystal shows the wave nature of photons. It is an important electromagnetic (EM) physics process when X-ray photons interact with a crystal. Bragg diffraction, often called Bragg reflection, is a special case of the general form of X-ray diffraction, known as Laue diffraction. When the Bragg's law is met, the incident photon beam is reflected from the crystal plane behaving as a specular reflection at the Bragg angle. However, the Bragg reflection physical process has not been integrated into the general-purpose Monte Carlo simulation toolkit Geant4 for particle physics. In the current study, we developed …