Medicine and Health Sciences Commons^™

Whole Genome Sequence Association Analysis Of Fasting Glucose And Fasting Insulin Levels In Diverse Cohorts From The Nhlbi Topmed Program, Daniel Dicorpo, Sheila M Gaynor, Emily M Russell, Kenneth E Westerman, Laura M Raffield, Timothy D Majarian, Peitao Wu, Chloé Sarnowski, Heather M Highland, Anne Jackson, Natalie R Hasbani, Paul S De Vries, Jennifer A Brody, Bertha Hidalgo, Xiuqing Guo, James A Perry, Jeffrey R O'Connell, Samantha Lent, May E Montasser, Brian E Cade, Deepti Jain, Heming Wang, Ricardo D'Oliveira Albanus, Arushi Varshney, Lisa R Yanek, Leslie Lange, Nicholette D Palmer, Marcio Almeida, Juan M Peralta, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Lawrence F Bielak, Chung-Shiuan Chen, Yii-Der Ida Chen, Won Jung Choi, Mark O Goodarzi, James S Floyd, Marguerite R Irvin, Rita R Kalyani, Tanika N Kelly, Seonwook Lee, Ching-Ti Liu, Douglas Loesch, Joann E Manson, Ryan L Minster, Take Naseri, James S Pankow, Laura J Rasmussen-Torvik, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Elizabeth Selvin, Jennifer A Smith, Daniel E Weeks, Huichun Xu, Jie Yao, Wei Zhao, Stephen Parker, Alvaro Alonso, Donna K Arnett, John Blangero, Eric Boerwinkle, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Ravindranath Duggirala, Jiang He, Susan R Heckbert, Sharon L R Kardia, Ryan W Kim, Charles Kooperberg, Simin Liu, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Alanna C Morrison, Patricia A Peyser, Bruce M Psaty, Susan Redline, Alan R Shuldiner, Kent D Taylor, Ramachandran S Vasan, Karine A Viaud-Martinez, Jose C Florez, James G Wilson, Robert Sladek, Stephen S Rich, Jerome I Rotter, Xihong Lin, Josée Dupuis, James B Meigs, Jennifer Wessel, Alisa K Manning

Faculty, Staff and Student Publications

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI's Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, …

Overall Survival With Brentuximab Vedotin In Stage Iii Or Iv Hodgkin's Lymphoma, Stephen M Ansell, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has …

The Lupus Susceptibility Allele Drb1*03:01 Encodes A Disease-Driving Epitope, Bruna Miglioranza Scavuzzi, Vincent Van Drongelen, Bhavneet Kaur, Jennifer Callahan Fox, Jianhua Liu, Raquel A Mesquita-Ferrari, J Michelle Kahlenberg, Evan A Farkash, Fernando Benavides, Frederick W Miller, Amr H Sawalha, Joseph Holoshitz

Faculty, Staff and Student Publications

The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal …

Family Physician Leadership During The Covid-19 Pandemic: Roles, Functions And Key Supports., Maria Mathews, Dana Ryan, Lindsay Hedden, Julia Lukewich, Emily Gard Marshall, Judith Belle Brown, Paul S Gill, Madeleine Mckay, Eric Wong, Stephen J Wetmore, Richard Buote, Leslie Meredith, Lauren Moritz, Sarah Spencer, Maria Alexiadis, Thomas R Freeman, Aimee Letto, Bridget L Ryan, Shannon L Sibbald, Amanda Lee Terry

Health Studies Publications

PURPOSE: Strong leadership in primary care is necessary to coordinate an effective pandemic response; however, descriptions of leadership roles for family physicians are absent from previous pandemic plans. This study aims to describe the leadership roles and functions family physicians played during the COVID-19 pandemic in Canada and identify supports and barriers to formalizing these roles in future pandemic plans.

DESIGN/METHODOLOGY/APPROACH: This study conducted semi-structured qualitative interviews with family physicians across four regions in Canada as part of a multiple case study. During the interviews, participants were asked about their roles during each pandemic stage and the facilitators and barriers …

Ketamine For Acute Pain After Trauma: The Kapt Randomized Controlled Trial, Thaddeus J Puzio, James Klugh, Michael W Wandling, Charles Green, Julius Balogh, Samuel J Prater, Christopher T Stephens, Paulina B Sergot, Charles E Wade, Lillian S Kao, John A Harvin

Faculty, Staff and Student Publications

BACKGROUND: Evidence for effective pain management and opioid minimization of intravenous ketamine in elective surgery has been extrapolated to acutely injured patients, despite limited supporting evidence in this population. This trial seeks to determine the effectiveness of the addition of sub-dissociative ketamine to a pill-based, opioid-minimizing multi-modal pain regimen (MMPR) for post traumatic pain.

METHODS: This is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing a MMPR to a MMPR plus a sub-dissociative ketamine infusion. All trauma patients 16 years and older admitted following a trauma which require intermediate (IMU) or intensive care unit (ICU) level of care are …

Targeting De Novo Lipogenesis And The Lands Cycle Induces Ferroptosis In Kras-Mutant Lung Cancer, Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett, Katerina Politi, Sandra L Starnes, Daniele Lorenzini, Maria Gabriela Raso, Luisa M Solis Soto, Carmen Behrens, Humam Kadara, Boning Gao, Ignacio I Wistuba, John D Minna, Jeffrey G Mcdonald, Pier Paolo Scaglioni

Faculty, Staff and Student Publications

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, …

Real-World Use Of Tisagenlecleucel In Infant Acute Lymphoblastic Leukemia., Amy Moskop, Lauren Pommert, Christina Baggott, Snehit Prabhu, Holly L. Pacenta, Christine L. Phillips, Jenna Rossoff, Heather E. Stefanski, Julie-An Talano, Steve P. Margossian, Michael R. Verneris, Douglas Myers, Nicole A. Karras, Patrick A. Brown, Muna Qayed, Michelle L. Hermiston, Prakash Satwani, Christa Krupski, Amy K. Keating, Rachel Wilcox, Cara A. Rabik, Vanessa A. Fabrizio, Vasant Chinnabhandar, A Yasemin Goksenin, Kevin J. Curran, Crystal L. Mackall, Theodore W. Laetsch, Erin M. Guest, Erin H. Breese, Liora M. Schultz

Manuscripts, Articles, Book Chapters and Other Papers

Infants with B-cell acute lymphoblastic leukemia (B-ALL) have poor outcomes because of chemotherapy resistance leading to high relapse rates. Tisagenlecleucel, a CD19-directed chimeric antigen receptor T-cell (CART) therapy, is US Food and Drug Administration approved for relapsed or refractory B-ALL in patients ≤25 years; however, the safety and efficacy of this therapy in young patients is largely unknown because children(n = 14). Sixty-four percent of patients (n = 9) achieved minimal residual disease-negative remission after CART and 50% of patients remain in remission at last follow-up. All patients with high disease burden at time of CART infusion (>M1 marrow) …

Activation Of Nano-Photosensitizers By Y-90 Microspheres To Enhance Oxidative Stress And Cell Death In Hepatocellular Carcinoma, Christopher D Malone, Christopher Egbulefu, Alexander Zheleznyak, Jahnavi Polina, Partha Karmakar, Kvar Black, Monica Shokeen, Samuel Achilefu

2020-Current year OA Pubs

While radioembolization with yttrium-90 (Y-90) microspheres is a promising treatment for hepatocellular carcinoma (HCC), lower responses in advanced and high-grade tumors present an urgent need to augment its tumoricidal efficacy. The purpose of this study was to determine whether clinically used Y-90 microspheres activate light-responsive nano-photosensitizers to enhance hepatocellular carcinoma (HCC) cell oxidative stress and cytotoxicity over Y-90 alone in vitro. Singlet oxygen and hydroxyl radical production was enhanced when Y-90 microspheres were in the presence of several nano-photosensitizers compared to either alone in cell-free conditions. Both the SNU-387 and HepG2 human HCC cells demonstrated significantly lower viability when treated …

Effect Of High- Vs Low-Dose Tranexamic Acid Infusion On Need For Red Blood Cell Transfusion And Adverse Events In Patients Undergoing Cardiac Surgery: The Optimal Randomized Clinical Trial, Jia Shi, Chenghui Zhou, Wei Pan, Hansong Sun, Sheng Liu, Wei Feng, Weijian Wang, Zhaoyun Cheng, Yang Wang, Zhe Zheng, Optimal Study Group

Faculty, Staff and Students Publications

IMPORTANCE: Tranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.

OBJECTIVE: To compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to …

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …

Persistent Ethnicity-Associated Disparity In Anti-Tumor Effectiveness Of Immune Checkpoint Inhibitors Despite Equal Access, Marcus A Florez, Jan O Kemnade, Nan Chen, Wendy Du, Anita L Sabichi, Daniel Y Wang, Quillan Huang, Courtney N Miller-Chism, Aparna Jotwani, Albert C Chen, David Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of …

Kstar: An Algorithm To Predict Patient-Specific Kinase Activities From Phosphoproteomic Data, Sam Crowl, Ben T Jordan, Hamza Ahmed, Cynthia X Ma, Kristen M Naegle

2020-Current year OA Pubs

Kinase inhibitors as targeted therapies have played an important role in improving cancer outcomes. However, there are still considerable challenges, such as resistance, non-response, patient stratification, polypharmacology, and identifying combination therapy where understanding a tumor kinase activity profile could be transformative. Here, we develop a graph- and statistics-based algorithm, called KSTAR, to convert phosphoproteomic measurements of cells and tissues into a kinase activity score that is generalizable and useful for clinical pipelines, requiring no quantification of the phosphorylation sites. In this work, we demonstrate that KSTAR reliably captures expected kinase activity differences across different tissues and stimulation contexts, allows for …

Characteristics Of Eating Behavior Profiles Among Preschoolers With Low-Income Backgrounds: A Person-Centered Analysis, Jennifer Orlet Fisher, Sheryl O Hughes, Alison L Miller, Mildred A Horodynski, Holly E Brophy-Herb, Dawn A Contreras, Niko Kaciroti, Karen E Peterson, Katherine L Rosenblum, Danielle Appugliese, Julie C Lumeng

Children’s Nutrition Research Center Staff Publications

Background: Individual differences in eating behaviors among young children are well-established, but the extent to which behaviors aggregate within individuals to form distinct eating behavior profiles remains unknown. Our objectives were to identify eating behavior profiles among preschool-aged children and evaluate associations with temperament and weight.

Methods: A secondary, cross-sectional analysis of baseline data from 2 cohort studies was conducted involving 1004 children aged 3-4 years and their parents with low-income backgrounds. Children's eating behaviors and temperament were assessed by parental report. Body mass index z-scores and weight status were calculated using measured heights and weights. Latent profile analysis (LPA) …

Molecular Profiles Of Serum-Derived Extracellular Vesicles In High-Grade Serous Ovarian Cancer, Li Zhao, Sara Corvigno, Shaolin Ma, Joseph Celestino, Nicole D Fleming, Richard A Hajek, Adrian Lankenau Ahumada, Nicholas B Jennings, Erika J Thompson, Hongli Tang, Shannon N Westin, Amir A Jazaeri, Jianhua Zhang, P Andrew Futreal, Anil K Sood, Sanghoon Lee

Faculty, Staff and Student Publications

Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified …

Two-Pore Channel Blockade By Phosphoinositide Kinase Inhibitors Ym201636 And Pi-103 Determined By A Histidine Residue Near Pore-Entrance, Canwei Du, Xin Guan, Jiusheng Yan

Faculty, Staff and Student Publications

Human two-pore channels (TPCs) are endolysosomal cation channels and play an important role in NAADP-evoked Ca2+ release and endomembrane dynamics. We found that YM201636, a PIKfyve inhibitor, potently inhibits PI(3,5)P2-activated human TPC2 with an IC50 of 0.16 μM. YM201636 also effectively inhibits NAADP-activated TPC2 and a constitutively-open TPC2 L690A/L694A mutant channel; whereas it exerts little effect when applied in the channel's closed state. PI-103, a YM201636 analog and an inhibitor of PI3K and mTOR, also inhibits human TPC2 with an IC50 of 0.64 μM. With mutational, virtual docking, and molecular dynamic simulation analyses, we found that YM201636 and PI-103 directly …

The Rsph4a Gene In Primary Ciliary Dyskinesia, Ron Nates, Mattan Arazi, Liza Grosman-Rimon, Roy Israel, Jacob Gohari, Leonid Sternik, Erez Kachel

Faculty, Staff and Student Publications

INTRODUCTION: There is no consensus as to which patients should undergo Non-Contrast Chest Computerized Tomography (NCCCT) and carotid arteries Doppler (CD) prior to cardiac surgery. The objective of this study was to examine whether preoperative imaging modalities provide clinical benefits and a change in surgical strategy.

METHODS: We routinely performed NCCCT and CD in all non-urgent cardiac surgery patients. Major NCCCT/CD findings related to cardiovascular findings (aortic calcification/atherosclerosis, carotid artery plaque/stenosis), or other incidental findings (lung kidney, thyroid, adrenal, gastrointestinal sites etc.) were documented. The results were divided into 3 categories: (A) findings requiring both changes in surgical strategy and …

Oilcloth Sessions As An Implementation Strategy: A Qualitative Study In Denmark, Jeanette Wassar Kirk, Nina Þórný Stefánsdóttir, Byron J Powell, Mette Bendtz Lindstroem, Ove Andersen, Tine Tjørnhøj-Thomsen, Per Nilsen

2020-Current year OA Pubs

BACKGROUND: The aim of this study was to explore healthcare professionals, managers, and other key employees' experiences of oilcloth sessions as a strategy when implementing new emergency departments in Denmark, based on their participations in these sessions. The study addresses the importance of securing alignment in implementation strategies. Too often, this does not get enough attention in the literature and in practice. In this study, alignment among components was achieved in an educational implementation strategy called oilcloth sessions.

METHODS: The study is based on participants' observations of 13 oilcloth sessions and follow-up via 53 semi-structured interviews with the board of …

Regulated Dicing Of Pre-Mir-144 Via Reshaping Of Its Terminal Loop., Renfu Shang, Dmitry A Kretov, Scott I Adamson, Thomas Treiber, Nora Treiber, Jeffrey Vedanayagam, Jeffrey H Chuang, Gunter Meister, Daniel Cifuentes, Eric C Lai

Faculty Research 2022

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2). We provide further evidence that this regulatory switch involves …

Influenza Activity And Composition Of The 2022-23 Influenza Vaccine - United States, 2021-22 Season, Angiezel Merced-Morales, Peter Daly, Anwar Isa Abd Elal, Noreen Ajayi, Ekow Annan, Alicia Budd, John Barnes, Arielle Colon, Charisse N Cummings, A Danielle Iuliano, Juliana Dasilva, Nick Dempster, Shikha Garg, Larisa Gubareva, Daneisha Hawkins, Amanda Howa, Stacy Huang, Marie Kirby, Krista Kniss, Rebecca Kondor, Jimma Liddell, Shunte Moon, Ha T Nguyen, Alissa O'Halloran, Catherine Smith, Thomas Stark, Katie Tastad, Dawud Ujamaa, Dave E Wentworth, Alicia M Fry, Vivien G Dugan, Lynnette Brammer

Faculty, Staff and Student Publications

Before the emergence of SARS-CoV-2, the virus that causes COVID-19, influenza activity in the United States typically began to increase in the fall and peaked in February. During the 2021-22 season, influenza activity began to increase in November and remained elevated until mid-June, featuring two distinct waves, with A(H3N2) viruses predominating for the entire season. This report summarizes influenza activity during October 3, 2021-June 11, 2022, in the United States and describes the composition of the Northern Hemisphere 2022-23 influenza vaccine. Although influenza activity is decreasing and circulation during summer is typically low, remaining vigilant for influenza infections, performing testing …

Myt1l In The Making: Emerging Insights On Functions Of A Neurodevelopmental Disorder Gene, Jiayang Chen, Allen Yen, Colin P Florian, Joseph D Dougherty

2020-Current year OA Pubs

Large scale human genetic studies have shown that loss of function (LoF) mutations in MYT1L are implicated in neurodevelopmental disorders (NDDs). Here, we provide an overview of the growing number of published MYT1L patient cases, and summarize prior studies in cells, zebrafish, and mice, both to understand MYT1L's molecular and cellular role during brain development and consider how its dysfunction can lead to NDDs. We integrate the conclusions from these studies and highlight conflicting findings to reassess the current model of the role of MYT1L as a transcriptional activator and/or repressor based on the biological context. Finally, we highlight additional …

Comparing Statistical Methods In Assessing The Prognostic Effect Of Biomarker Variability On Time-To-Event Clinical Outcomes, Feng Gao, Jingqin Luo, Jingxia Liu, Fei Wan, Guoqiao Wang, Mae Gordon, Chengjie Xiong

2020-Current year OA Pubs

BACKGROUND: In recent years there is increasing interest in modeling the effect of early longitudinal biomarker data on future time-to-event or other outcomes. Sometimes investigators are also interested in knowing whether the variability of biomarkers is independently predictive of clinical outcomes. This question in most applications is addressed via a two-stage approach where summary statistics such as variance are calculated in the first stage and then used in models as covariates to predict clinical outcome in the second stage. The objective of this study is to compare the relative performance of various methods in estimating the effect of biomarker variability. …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma., Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Faculty Research 2022

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Understanding The Role Of Sex On Outcomes For The Cancer Patient Undergoing Treatment With Immune Checkpoint Inhibitors: A Scoping Review Protocol, Amy L Shaver, Nikita Nikita, Swapnil Sharma, Daniel S Lefler, Atrayee Basu-Mallick, Jennifer M Johnson, Meghan L Butryn, Grace Lu-Yao

Department of Medical Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the …

Advanced-Stage Melanoma At Presentation Following The Peak Of The Pandemic: A Covid-19 Cancer Canary In A Coal Mine, Ryan Lamm, Md, Walker Lyons, Md, Winnie So, Rn, Alliric I. Willis, Md, Facs, Msph

Department of Surgery Faculty Papers

Background: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline.

Methods: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables …

Tumor Microenvironment In Pancreatic Ductal Adenocarcinoma: Implications In Immunotherapy, Caitlyn Smith, Wei Zheng, Jixin Dong, Yaohong Wang, Jinping Lai, Xiuli Liu, Feng Yin

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma, Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Center for Medical Ethics and Health Policy Staff Publications

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Graded Variation In T1w/T2w Ratio During Adolescence: Measurement, Caveats, And Implications For Development Of Cortical Myelin, Graham L Baum, John C Flournoy, Matthew F Glasser, Michael P Harms, Patrick Mair, Ashley F P Sanders, Deanna M Barch, Randy L Buckner, Susan Bookheimer, Mirella Dapretto, Stephen Smith, Kathleen M Thomas, Essa Yacoub, David C Van Essen, Leah H Somerville

2020-Current year OA Pubs

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D;

Changes In Health Care Access During The Covid-19 Pandemic: Estimates Of National Japanese Data, June 2020-October 2021, Yuta Tanoue, Cyrus Ghaznavi, Takayuki Kawashima, Akifumi Eguchi, Daisuke Yoneoka, Shuhei Nomura

2020-Current year OA Pubs

The COVID-19 pandemic has disrupted health care access around the world, both for inpatients and outpatients. We applied a quasi-Poisson regression to national, monthly data on the number of outpatients, number of inpatients, length of average hospital stay, and the number of new hospitalizations from March 2015 to October 2021 to assess how these outcomes changed between June 2020 to October 2021. The number of outpatient visits were lower-than-predicted during the early phases of the pandemic but normalized by the fall of 2021. The number of inpatients and new hospitalizations were lower-than-predicted throughout the pandemic, and deficits in reporting continued …

Kathryn V. Holmes: A Career Of Contributions To The Coronavirus Field, Aurelio Bonavia, Samuel R Dominguez, Gabriela Dveksler, Sara Gagneten, Megan Howard, Scott Jeffers, Zhaohui Qian, Mary Kathryn Smith, Larissa B Thackray, Dina B Tresnan, David E Wentworth, David R Wessner, Richard K Williams, Tanya A Miura

2020-Current year OA Pubs

Over the past two years, scientific research has moved at an unprecedented rate in response to the COVID-19 pandemic. The rapid development of effective vaccines and therapeutics would not have been possible without extensive background knowledge on coronaviruses developed over decades by researchers, including Kathryn (Kay) Holmes. Kay's research team discovered the first coronavirus receptors for mouse hepatitis virus and human coronavirus 229E and contributed a wealth of information on coronaviral spike glycoproteins and receptor interactions that are critical determinants of host and tissue specificity. She collaborated with several research laboratories to contribute knowledge in additional areas, including coronaviral pathogenesis, …

Proteomic Biomarkers Of The Apnea Hypopnea Index And Obstructive Sleep Apnea: Insights Into The Pathophysiology Of Presence, Severity, And Treatment Response, Katie L J Cederberg, Yo-El S Ju, Et Al

2020-Current year OA Pubs

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (