Digital Commons Network^™

Short-Term Biomarker Modulation Study Of Dasatinib For Estrogen Receptor-Negative Breast Cancer Chemoprevention, Fatma Nihan Akkoc Mustafayev, Diane D Liu, Angelica M Gutierrez, John E Lewis, Nuhad K Ibrahim, Vicente Valero, Daniel J Booser, Jennifer K Litton, Kimberly Koenig, Dihua Yu, Nour Sneige, Banu K Arun

Faculty, Staff and Student Publications

OBJECTIVE: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer.

MATERIALS AND METHODS: Women with a history of unilateral stage I, II, …

Serum Metabolomic Markers Of Dairy Consumption: Results From The Atherosclerosis Risk In Communities Study And The Bogalusa Heart Study, Lauren Bernard, Jingsha Chen, Hyunju Kim, Zhijie Huang, Lydia Bazzano, Lu Qi, Jiang He, Varun S Rao, Kaitlin S Potts, Tanika N Kelly, Kari E Wong, Lyn M Steffen, Bing Yu, Eugene P Rhee, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake.

OBJECTIVES: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults.

METHODS: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study …

Lowering Of Circulating Sclerostin May Increase Risk Of Atherosclerosis And Its Risk Factors: Evidence From A Genome-Wide Association Meta-Analysis Followed By Mendelian Randomization, Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till F M Andlauer, Michelle S Yau, April E Hartley, Ben Michael Brumpton, Humaira Rasheed, John P Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A Peyser, Maryam Kavousi, Paul S De Vries, Clint L Miller, Maxime Bos, Sander W Van Der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V Holmes, George Davey Smith, Jonathan H Tobias

Faculty, Staff and Student Publications

OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors.

METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors.

RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and …

Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.

METHODS: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules …

Diabetes Risk During Pregnancy Among Second-Generation Immigrants: A National Cohort Study In Sweden, Per Wändell, Xinjun Li, Nouha Saleh Stattin, Axel C Carlsson, Jan Sundquist, Casey Crump, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy.

METHODS AND RESULTS: A cohort study was conducted using the Swedish National Birth Register, the National Patient Register, and the total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% confidence intervals (99% CI) for any diabetes during pregnancy and specific …

The Emerging Importance Of Mitochondria In White Adipocytes: Neither Last Nor Least, Juan Cai, Fenfen Wang, Mengle Shao

Faculty, Staff and Student Publications

The growing recognition of mitochondria's crucial role in the regulation of white adipose tissue remodeling and energy balance underscores its significance. The marked metabolic diversity of mitochondria provides the molecular and cellular foundation for enabling adipose tissue plasticity in response to various metabolic cues. Effective control of mitochondrial function at the cellular level, not only in thermogenic brown and beige adipocytes but also in energy-storing white adipocytes, exerts a profound influence on adipose homeostasis. Furthermore, mitochondria play a pivotal role in intercellular communication within adipose tissue via production of metabolites with signaling properties. A more comprehensive understanding of mitochondrial regulation …

Suspected Bronchiectasis And Mortality In Adults With A History Of Smoking Who Have Normal And Impaired Lung Function : A Cohort Study, Alejandro A Diaz, Wei Wang, Jose L Orejas, Rim Elalami, Wojciech R Dolliver, Pietro Nardelli, Ruben San José Estépar, Bina Choi, Carrie L Pistenmaa, James C Ross, Diego J Maselli, Andrew Yen, Kendra A Young, Gregory L Kinney, Michael H Cho, Raul San José Estépar

Faculty, Staff and Student Publications

Background: Bronchiectasis in adults with chronic obstructive pulmonary disease (COPD) is associated with greater mortality. However, whether suspected bronchiectasis-defined as incidental bronchiectasis on computed tomography (CT) images plus clinical manifestation-is associated with increased mortality in adults with a history of smoking with normal spirometry and preserved ratio impaired spirometry (PRISm) is unknown.

Objective: To determine the association between suspected bronchiectasis and mortality in adults with normal spirometry, PRISm, and obstructive spirometry.

Design: Prospective, observational cohort.

Setting: The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study.

Participants: 7662 non-Hispanic Black or White adults, aged 45 to 80 years, with 10 …

Baseline Psychosocial, Environmental, Health, And Behavioral Correlates Of 1- And 3-Year Weight Loss After Bariatric Surgery, Ming Ji, Sonya L Negriff, Jeff M Slezak, Brianna L Taylor, Silvia R Paz, Bhumi B Bhakta, Mayra Macias, David E Arterburn, Cecelia L Crawford, Adam Drewnowski, Kristina H Lewis, Darren D Moore, Sameer B Murali, Deborah R Young, Karen J Coleman

Faculty, Staff and Student Publications

PURPOSE: Weight loss surgery is an effective, long-term treatment for severe obesity but individual response to surgery varies widely. The purpose of this study was to test a comprehensive theoretical model of factors that may be correlated with the greatest surgical weight loss at 1-3 years following surgery. Such a model would help determine what predictive factors to measure when patients are preparing for surgery that may ensure the best weight outcomes.

MATERIALS AND METHODS: The Bariatric Experience Long Term (BELONG) study collected self-reported and medical record-based baseline information as correlates of 1- and 3-year % total weight loss (TWL) …

Risk Factors For Overweight And Obesity After Childhood Acute Lymphoblastic Leukemia In North America And Switzerland: A Comparison Of Two Cohort Studies, Fabiën N Belle, Christina Schindera, Marc Ansari, Gregory T Armstrong, Maja Beck-Popovic, Rebecca Howell, Wendy M Leisenring, Lillian R Meacham, Jochen Rössler, Ben D Spycher, Emily Tonorezos, Nicolas X Von Der Weid, Yutaka Yasui, Kevin C Oeffinger, Claudia E Kuehni

Faculty, Staff and Student Publications

Background: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors.

Methods: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in …

Dietary Intake And Quality Among Stroke Survivors: Nhanes 1999-2018, Erika R Zoellner, Mindy A Patterson, Anjail Z Sharrief, Sean I Savitz, Wesley J Tucker, Derek C Miketinas

Faculty, Staff and Student Publications

Background: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited.

Objectives: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke.

Methods: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of …

Diagnosis Of Chronic Pancreatitis Using Semi-Quantitative Mri Features Of The Pancreatic Parenchyma: Results From The Multi-Institutional Minimap Study, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls.

Methods: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) …

Circulating Short Chain Fatty Acids And Fatigue In Patients With Head And Neck Cancer: A Longitudinal Prospective Study, Canhua Xiao, Veronika Fedirko, Henry Claussen, H Richard Johnston, Gang Peng, Sudeshna Paul, Kristal M Maner-Smith, Kristin A Higgins, Dong M Shin, Nabil F Saba, Evanthia C Wommack, Deborah W Bruner, Andrew H Miller

Faculty, Staff and Student Publications

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = …

Aspergillus Flavus And Fusarium Verticillioides And Their Main Mycotoxins: Global Distribution And Scenarios Of Interactions In Maize, Xiangrong Chen, Mohamed F Abdallah, Sofie Landschoot, Kris Audenaert, Sarah De Saeger, Xiangfeng Chen, Andreja Rajkovic

Faculty, Staff and Student Publications

Maize is frequently contaminated with multiple mycotoxins, especially those produced by Aspergillus flavus and Fusarium verticillioides. As mycotoxin contamination is a critical factor that destabilizes global food safety, the current review provides an updated overview of the (co-)occurrence of A. flavus and F. verticillioides and (co-)contamination of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) in maize. Furthermore, it summarizes their interactions in maize. The gathered data predict the (co-)occurrence and virulence of A. flavus and F. verticillioides would increase worldwide, especially in European cold climate countries. Studies on the interaction of both fungi regarding their growth mainly showed antagonistic …

Protocol For Expression Of Murine Milk Using Modified Human Breast Pump Parts, Cydney Meyer, Joseph L Alcorn

Faculty, Staff and Student Publications

Understanding the nutritional and immunomodulatory components of breast milk is crucial to developing novel mechanisms to optimize neonatal health. Here, we present a protocol to express and isolate murine milk in sufficient quantities for further analysis of components and bioactivity. We describe steps for separating dams from pups, administering intraperitoneal anesthetic and oxytocin, and expressing milk using a minimally modified and readily available commercial breast pump parts. For complete details on the use and execution of this protocol, please refer to Meyer et al. (2022).

The Impact Of Insomnia Symptoms On Obesity Among Mexicans Aged 50 And Older, Kanwal N Momin, Connor Sheehan, Rafael Samper-Ternent, David S López, Rebeca Wong, Sadaf Arefi Milani

Faculty, Staff and Student Publications

OBJECTIVE: To examine the association between insomnia and obesity in Mexican adults aged 50 and older.

MATERIALS AND METHODS: We used data from the Mexican Health and Aging Study (2015-2018). Self-reported insomnia was measured using the modified insomnia severity index with scores ranging from zero to six. Obesity was categorized using body mass index (BMI ≥ 30 kg/m2). We used generalized estimating equations to assess the association between insomnia and obesity over three years.

RESULTS: Insomnia was associated with obesity (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01,1.11), among those with no obesity at baseline. Among those with obesity, …

Notes From The Field: Online Weight Loss Supplements Labeled As Tejocote (Crataegus Mexicana) Root, Substituted With Yellow Oleander (Cascabela Thevetia) - United States, 2022, Noah Berland, James Kababick, Cynthia Santos, Diane P Calello

Faculty, Staff and Student Publications

No abstract provided.

Direct Modulators Of K-Ras–Membrane Interactions, Johannes Morstein, Rebika Shrestha, Que N Van, César A López, Neha Arora, Marco Tonelli, Hong Liang, De Chen, Yong Zhou, John F Hancock, Andrew G Stephen, Thomas J Turbyville, Kevan M Shokat

Faculty, Staff and Student Publications

Protein-membrane interactions (PMIs) are ubiquitous in cellular signaling. Initial steps of signal transduction cascades often rely on transient and dynamic interactions with the inner plasma membrane leaflet to populate and regulate signaling hotspots. Methods to target and modulate these interactions could yield attractive tool compounds and drug candidates. Here, we demonstrate that the conjugation of a medium-chain lipid tail to the covalent K-Ras(G12C) binder MRTX849 at a solvent-exposed site enables such direct modulation of PMIs. The conjugated lipid tail interacts with the tethered membrane and changes the relative membrane orientation and conformation of K-Ras(G12C), as shown by molecular dynamics (MD) …

Unfolding The Secrets Of Small Cell Lung Cancer Progression: Novel Approaches And Insights Through Rapid Autopsies, Zsolt Megyesfalvi, Simon Heeke, Benjamin J Drapkin, Anna Solta, Ildiko Kovacs, Kristiina Boettiger, Lilla Horvath, Busra Ernhofer, Janos Fillinger, Ferenc Renyi-Vamos, Clemens Aigner, Karin Schelch, Christian Lang, Gyorgy Marko-Varga, Carl M Gay, Lauren A Byers, Benjamin B Morris, John V Heymach, Peter Van Loo, Fred R Hirsch, Balazs Dome

Faculty, Staff and Student Publications

The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.

Sex Hormone-Binding Globulin (Shbg) Mitigates Er Stress And Improves Viability And Insulin Sensitivity In Adipose-Derived Mesenchymal Stem Cells (Asc) Of Equine Metabolic Syndrome (Ems)-Affected Horses, Nabila Bourebaba, Mateusz Sikora, Badr Qasem, Lynda Bourebaba, Krzysztof Marycz

Faculty, Staff and Student Publications

BACKGROUND: Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASC

METHODS: EqASC

RESULTS: Obtained data demonstrated that exogenous SHBG treatment significantly promoted ASCs cells proliferation, cell cycle and survival with reduced …

The Classification Of Obesity Based On Metabolic Status Redefines The Readmission Of Non-Hodgkin’S Lymphoma—An Observational Study, Eunju Kim, Kazuaki Mawatari, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

Obesity is a known risk factor for metabolic diseases and is often associated with chronic inflammation in adipose tissue. We previously identified the polyethoxylated flavonoid Nobiletin (NOB) as a circadian clock modulator that directly binds to and activates the ROR receptors in the core oscillator, markedly improving metabolic fitness in obese mice. Here, we show that NOB enhanced the oscillation of core clock genes in differentiated 3T3-L1 adipocytes, including ROR target genes such as Bmal1, Cry1, Dec1, and Dec2. NOB inhibited lipid accumulation in 3T3-L1 and SVF cells, concomitant with the dysregulated circadian expression of adipogenic …

Evaluation Of In Vitro Antioxidant, Anti-Obesity, And Anti-Diabetic Activities Of, Alaa S Mohamed, Essam Mohamed Elsebaie, Wesam Mohammed Abdelrhman, Nabila Yahia Mahmoud Abdulmaguid, Rasha M Bahnasy, Manal Salah Abbas Elgendy, Arwa Mohamed Mohamed Mahmoud Elashry, Marwa Fawzy El-Hassanin, Nora Hamdy Mouhamed El-Wakeil, Azhar Mostafa Mohamed Khalil, Hesham F Amin

Faculty, Staff and Student Publications

Opuntia ficus cladodes (OFC) are considered one of the wastes that result from opuntia cultivation, and their disposal by traditional methods results in many environmental problems. Therefore, this study was conducted with two aims. The first was the production of OFC gel, and the evaluation of its in vitro antioxidant (by two methods, DPPH and ABTS), anti-obesity, and anti-diabetic activities. The second was an investigation of the effects of different concentrations of this gel (0, 50, and 100%) as an edible coating on the quality of shrimp during 8 days of refrigerated storage. The results showed that this gel was …

Development Of A Culturally Adapted Dietary Intervention To Reduce Alzheimer's Disease Risk Among Older Black Adults, Ashley R Shaw, Mickeal N Key, Samantha Fikru, Saria Lofton, Debra K Sullivan, Jannette Berkley-Patton, Crystal M Glover, Jeffrey M Burns, Eric D Vidoni

Faculty, Staff and Student Publications

The objective of this study is to identify and understand knowledge and attitudes that influence dietary practices among older Black adults using a community-engaged approach. This is a non-interventional mixed methods study designed to inform the development of an adapted brain-healthy soul food diet intervention. A purposive sampling approach was used to conduct seven semi-structured focus group discussions and an online quantitative survey. In total, 39 participants who self-identified as Black, aged 55 years and older, English speaking, and who were cognitively normal with an AD8 < 2; (25.6% men; 74.4% women) participated in the online survey and one of the seven 60 min virtual focus group discussions (5-7 per focus group). Quantitative frequency data from the online surveys were analyzed using descriptive statistics. Qualitative focus group data were analyzed using a 6-step thematic analysis process. Five themes emerged: dementia awareness; practices shaping food choices and consumption; barriers to eating healthy; instrumental support; and elements of a culturally adapted brain-healthy dietary intervention. Older Black adults perceived an adapted MIND dietary model as the most acceptable with the incorporation of salient cultural characteristics and strategies within both the design and delivery phases.

Hospitalizations Among Adults With Ckd In Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia, Vishal Diwan, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

RATIONALE & OBJECTIVE: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT).

STUDY DESIGN: Retrospective observational cohort study.

SETTING & PARTICIPANTS: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018.

PREDICTORS: Demographic and clinical characteristics of patients with CKD.

OUTCOMES: Hospital admissions.

ANALYTICAL APPROACH: We evaluated the association of demographic and clinical features with hospitalizations, length …

Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing

Faculty, Staff and Student Publications

Interleukin (IL)-10 was one of the first cytokines to be recognized. However, its functionality in promoting antitumor immunity was described more recently. Context- and concentration-dependent biological effects are the hallmarks of the pleiotropic role of IL-10. Despite reducing tumor-promoting inflammation, IL-10 may have a role in rejuvenating exhausted tumor-resident T cells. Contrary to the assumption that IL-10 produces an immunosuppressive tumor microenvironment (TME), it promotes activation of tumor-resident CD8+ T cells, which aids tumor rejection. Emerging data from published early-Phase trials have shown mixed results in different tumor types. In this review, we summarize the biological effects of IL-10 and …

Emotional Distress And Cardiovascular Disease Risk Among Participants Enrolled In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study, Gladys Crespo-Ramos, Ionut Bebu, Heidi Krause-Steinrauf, Claire J Hoogendoorn, Ran Fang, Dominic Ehrmann, Caroline Presley, Aanand D Naik, Aimee Katona, Elizabeth A Walker, Andrea Cherrington, Jeffrey S Gonzalez

Faculty, Staff and Student Publications

AIMS: People with type 2 diabetes (T2DM) have an increased risk of cardiovascular disease (CVD). We examined depressive symptoms (DS) and diabetes distress (DD) in relation to the estimated 10-year risk of CVD in adults with T2DM enrolled in the GRADE Emotional Distress Substudy.

METHODS: Linear regression models examined the associations of baseline DS and DD with estimated 10-year risk of CVD using the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, adjusting for age, sex, race/ethnicity, education, income, diabetes duration, diabetes-related complications, and HbA1c.

RESULTS: A total of 1,605 GRADE participants were included: 54% Non-Latino (NL) White, 18% Latino, 19% NL-Black, …

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

Use Of Compartmental Modeling And Retinol Isotope Dilution To Determine Vitamin A Stores In Young People With Sickle Cell Disease Before And After Vitamin A Supplementation, Jennifer Lynn Ford, Michael H Green, Jefferson N Brownell, Joanne Balmer Green, Anthony Oxley, Georg Lietz, Joan I Schall, Virginia A Stallings

Faculty, Staff and Student Publications

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD.

OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects.

METHODS: Composite plasma [

RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 μmol, equivalent to ∼11 mo of stored vitamin …

Risk Factors For Perinatal Transmission Of Hepatitis C Virus, Mona Prasad, George R Saade, Rebecca G Clifton, Grecio J Sandoval, Brenna L Hughes, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, Mobeen Rathore, Rodrigo Diaz-Velasco, Ana M Puga, Andrew Wiznia, Andrea Kovacs, David J Garry, George A Macones, For The Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network*

Faculty, Staff and Student Publications

Objective: To estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission.

Methods: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) …

Correction: “The 5th Edition Of The World Health Organization Classification Of Haematolymphoid Tumours: Lymphoid Neoplasms” Leukemia 2022 Jul; 36(7):1720–1748, Rita Alaggio, Catalina Amador, Ioannis Anagnostopoulos, Ayoma D Attygalle, Iguaracyra Barreto De Oliveira Araujo, Emilio Berti, Govind Bhagat, Anita Maria Borges, Daniel Boyer, Mariarita Calaminici, Amy Chadburn, John K C Chan, Wah Cheuk, Wee-Joo Chng, John K Choi, Shih-Sung Chuang, Sarah E Coupland, Magdalena Czader, Sandeep S Dave, Daphne De Jong, Arianna Di Napoli, Ming-Qing Du, Kojo S Elenitoba-Johnson, Judith Ferry, Julia Geyer, Dita Gratzinger, Joan Guitart, Sumeet Gujral, Marian Harris, Christine J Harrison, Sylvia Hartmann, Andreas Hochhaus, Patty M Jansen, Kennosuke Karube, Werner Kempf, Joseph Khoury, Hiroshi Kimura, Wolfram Klapper, Alexandra E Kovach, Shaji Kumar, Alexander J Lazar, Stefano Lazzi, Lorenzo Leoncini, Nelson Leung, Vasiliki Leventaki, Xiao-Qiu Li, Megan S Lim, Wei-Ping Liu, Abner Louissaint, Andrea Marcogliese, L Jeffrey Medeiros, Michael Michal, Roberto N Miranda, Christina Mitteldorf, Santiago Montes-Moreno, William Morice, Valentina Nardi, Kikkeri N Naresh, Yasodha Natkunam, Siok-Bian Ng, Ilske Oschlies, German Ott, Marie Parrens, Melissa Pulitzer, S Vincent Rajkumar, Andrew C Rawstron, Karen Rech, Andreas Rosenwald, Jonathan Said, Clémentine Sarkozy, Shahin Sayed, Caner Saygin, Anna Schuh, William Sewell, Reiner Siebert, Aliyah R Sohani, Ritsuro Suzuki, Reuben Tooze, Alexandra Traverse-Glehen, Francisco Vega, Beatrice Vergier, Ashutosh D Wechalekar, Brent Wood, Luc Xerri, Wenbin Xiao

Faculty, Staff and Student Publications

No abstract provided.