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Craniofacial Bone Anomalies Related To Cholesterol Synthesis Defects, Chihiro Iwaya, Akiko Suzuki, Junbo Shim, Aemin Kim, Junichi Iwata Mar 2024

Craniofacial Bone Anomalies Related To Cholesterol Synthesis Defects, Chihiro Iwaya, Akiko Suzuki, Junbo Shim, Aemin Kim, Junichi Iwata

Faculty, Staff and Student Publications

DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7


Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir Mar 2024

Differential Treatment Effects Of Subgroup Analyses In Phase 3 Oncology Trials From 2004 To 2020, Alexander D Sherry, Andrew W Hahn, Zachary R Mccaw, Joseph Abi Jaoude, Ramez Kouzy, Timothy A Lin, Bruce Minsky, C David Fuller, Tomer Meirson, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Importance: Subgroup analyses are often performed in oncology to investigate differential treatment effects and may even constitute the basis for regulatory approvals. Current understanding of the features, results, and quality of subgroup analyses is limited.

Objective: To evaluate forest plot interpretability and credibility of differential treatment effect claims among oncology trials.

Design, setting, and participants: This cross-sectional study included randomized phase 3 clinical oncology trials published prior to 2021. Trials were screened from ClinicalTrials.gov.

Main outcomes and measures: Missing visual elements in forest plots were defined as a missing point estimate or use of a linear x-axis scale for hazard …


Values, Challenges, And Responses Associated With High-Priced Potential Cures: Perspectives Of Diverse Stakeholders In South Korea, Jihyung Hong, Eun-Young Bae, Hye-Jae Lee, Tae-Jin Lee, Philip Clarke Mar 2024

Values, Challenges, And Responses Associated With High-Priced Potential Cures: Perspectives Of Diverse Stakeholders In South Korea, Jihyung Hong, Eun-Young Bae, Hye-Jae Lee, Tae-Jin Lee, Philip Clarke

Faculty, Staff and Student Publications

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies.

METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online …


The Identification Of A Distinct Astrocyte Subtype That Diminishes In Alzheimer's Disease, Haichao Wei, Joseph Withrow, Jyotirmoy Rakshit, Faiz Ul Amin, Joshua Nahm, Francesca E Mowry, Zhengmei Mao, Meenakshi B Bhattacharjee, Jay-Jiguang Zhu, Yongjie Yang, Jia Qian Wu Mar 2024

The Identification Of A Distinct Astrocyte Subtype That Diminishes In Alzheimer's Disease, Haichao Wei, Joseph Withrow, Jyotirmoy Rakshit, Faiz Ul Amin, Joshua Nahm, Francesca E Mowry, Zhengmei Mao, Meenakshi B Bhattacharjee, Jay-Jiguang Zhu, Yongjie Yang, Jia Qian Wu

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is characterized by the presence of two hallmark pathologies: the accumulation of Amyloid beta (Aβ) and tau proteins in the brain. There is a growing body of evidence suggesting that astrocytes, a type of glial cell in the brain, play crucial roles in clearing Aβ and binding to tau proteins. However, due to the heterogeneity of astrocytes, the specific roles of different astrocyte subpopulations in response to Aβ and tau remain unclear. To enhance the understanding of astrocyte subpopulations in AD, we investigated astrocyte lineage cells based on single-nuclei transcriptomic data obtained from both human and mouse …


Outcomes In Biomarker-Selected Subgroups From The Kestrel Study Of Durvalumab And Tremelimumab In Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma, Tanguy Y Seiwert, Sophie Wildsmith, Jérôme Fayette, Kevin Harrington, Maura Gillison, Myung-Ju Ahn, Shunji Takahashi, Jared Weiss, Jean-Pascal Machiels, Shrujal Baxi, Valerie Baker, Brent Evans, Nassim Morsli, Jill Walker, Katia Real, Anne L'Hernault, Amanda Psyrri Mar 2024

Outcomes In Biomarker-Selected Subgroups From The Kestrel Study Of Durvalumab And Tremelimumab In Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma, Tanguy Y Seiwert, Sophie Wildsmith, Jérôme Fayette, Kevin Harrington, Maura Gillison, Myung-Ju Ahn, Shunji Takahashi, Jared Weiss, Jean-Pascal Machiels, Shrujal Baxi, Valerie Baker, Brent Evans, Nassim Morsli, Jill Walker, Katia Real, Anne L'Hernault, Amanda Psyrri

Faculty, Staff and Student Publications

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).

METHODS: Tumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective …


Global Trend In Exosome Isolation And Application: An Update Concept In Management Of Diseases, Mohammadhassan Omrani, Hanieh Beyrampour-Basmenj, Rana Jahanban-Esfahlan, Mahnaz Talebi, Mortaza Raeisi, Zeinab Aliyari Serej, Naeimeh Akbar-Gharalari, Sina Khodakarimi, Jiaqian Wu, Abbas Ebrahimi-Kalan Mar 2024

Global Trend In Exosome Isolation And Application: An Update Concept In Management Of Diseases, Mohammadhassan Omrani, Hanieh Beyrampour-Basmenj, Rana Jahanban-Esfahlan, Mahnaz Talebi, Mortaza Raeisi, Zeinab Aliyari Serej, Naeimeh Akbar-Gharalari, Sina Khodakarimi, Jiaqian Wu, Abbas Ebrahimi-Kalan

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, …


The Lymphoma Epidemiology Of Outcomes Cohort Study: Design, Baseline Characteristics, And Early Outcomes, James R Cerhan, Matthew J Maurer, Brian K Link, Andrew L Feldman, Thomas M Habermann, David L Jaye, W Richard Burack, Timothy J Mcdonnell, Francisco Vega, Jennifer R Chapman, Sergei Syrbu, Kiran R Vij, Giorgio Inghirami, John P Leonard, Leon Bernal-Mizrachi, Umar Farooq, Thomas E Witzig, George J Weiner, Yucai Wang, Juan P Alderuccio, Susan L Slager, Melissa C Larson, Shaun M Riska, Brianna J Gysbers, Julianne J Lunde, Tanner W Reicks, Amy A Ayers, Colin B O'Leary, Kathleen J Yost, Hongfang Liu, Grzegorz S Nowakowski, Jia Ruan, Dai Chihara, Jean L Koff, Carla Casulo, Carrie A Thompson, Jonathon B Cohen, Brad S Kahl, Loretta J Nastoupil, Izidore S Lossos, Jonathan W Friedberg, Peter Martin, Christopher R Flowers Mar 2024

The Lymphoma Epidemiology Of Outcomes Cohort Study: Design, Baseline Characteristics, And Early Outcomes, James R Cerhan, Matthew J Maurer, Brian K Link, Andrew L Feldman, Thomas M Habermann, David L Jaye, W Richard Burack, Timothy J Mcdonnell, Francisco Vega, Jennifer R Chapman, Sergei Syrbu, Kiran R Vij, Giorgio Inghirami, John P Leonard, Leon Bernal-Mizrachi, Umar Farooq, Thomas E Witzig, George J Weiner, Yucai Wang, Juan P Alderuccio, Susan L Slager, Melissa C Larson, Shaun M Riska, Brianna J Gysbers, Julianne J Lunde, Tanner W Reicks, Amy A Ayers, Colin B O'Leary, Kathleen J Yost, Hongfang Liu, Grzegorz S Nowakowski, Jia Ruan, Dai Chihara, Jean L Koff, Carla Casulo, Carrie A Thompson, Jonathon B Cohen, Brad S Kahl, Loretta J Nastoupil, Izidore S Lossos, Jonathan W Friedberg, Peter Martin, Christopher R Flowers

Faculty, Staff and Student Publications

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 >years, and 1513 rural residents. At study baseline, we abstracted clinical, …


Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group Mar 2024

Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group

Faculty, Staff and Student Publications

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a …


The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett Mar 2024

The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett

Faculty, Staff and Student Publications

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence


Endosteal Stem Cells At The Bone-Blood Interface: A Double-Edged Sword For Rapid Bone Formation: Bone Marrow Endosteal Stem Cells Provide A Robust Source Of Bone-Making Osteoblasts Both In Normal And Abnormal Bone Formation, Yuki Matsushita, Jialin Liu, Angel Ka Yan Chu, Wanida Ono, Joshua D Welch, Noriaki Ono Mar 2024

Endosteal Stem Cells At The Bone-Blood Interface: A Double-Edged Sword For Rapid Bone Formation: Bone Marrow Endosteal Stem Cells Provide A Robust Source Of Bone-Making Osteoblasts Both In Normal And Abnormal Bone Formation, Yuki Matsushita, Jialin Liu, Angel Ka Yan Chu, Wanida Ono, Joshua D Welch, Noriaki Ono

Faculty, Staff and Student Publications

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non-endosteal perisinusoidal niche. Single-cell molecular profiling and in vivo cell lineage analyses play key roles in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor-making cells when deleterious mutations occur in …


Metabolomic Association And Risk Prediction With Heart Failure In Older Adults, Guning Liu, Ngoc Quynh H Nguyen, Kari E Wong, Sunil K Agarwal, Eric Boerwinkle, Patricia P Chang, Brian L Claggett, Laura R Loehr, Jianzhong Ma, Kunihiro Matsushita, Carlos J Rodriguez, Joseph S Rossi, Stuart D Russell, R Brandon Stacey, Amil M Shah, Bing Yu Mar 2024

Metabolomic Association And Risk Prediction With Heart Failure In Older Adults, Guning Liu, Ngoc Quynh H Nguyen, Kari E Wong, Sunil K Agarwal, Eric Boerwinkle, Patricia P Chang, Brian L Claggett, Laura R Loehr, Jianzhong Ma, Kunihiro Matsushita, Carlos J Rodriguez, Joseph S Rossi, Stuart D Russell, R Brandon Stacey, Amil M Shah, Bing Yu

Faculty, Staff and Student Publications

Background: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

Methods: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score …


Practical Considerations For Navigating Withdrawal From The Federal Select Agent Program, Scott J Patlovich, Kristin G King, Robert J Emery, Zackary B Becker, Rebecca B Kairis Mar 2024

Practical Considerations For Navigating Withdrawal From The Federal Select Agent Program, Scott J Patlovich, Kristin G King, Robert J Emery, Zackary B Becker, Rebecca B Kairis

Faculty, Staff and Student Publications

INTRODUCTION: Clear guidance is provided by the Federal Select Agent Program (FSAP) to assist registered entities in nearly all facets of compliance with the Federal select agent regulations (7 CFR Part 331; 9 CFR Part 121; 42 CFR Part 73). If a registered entity chooses to discontinue its registration, detailed instructions for registration withdrawal are deeply embedded within a document entitled "eFSAP Form 1 Amendment Instructions," which is found on the FSAP website within the electronic Federal Select Agent Program (eFSAP) Resource Center.

METHODS: Using the information found within the eFSAP Form 1 Amendment Instructions, as well as extensive written …


Plasma Protein Signatures Of Adult Asthma, Gordon J Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B Wyss, Julie D White, Sinjini Sikdar, Jianping Jin, Andrew J Grant, Alison A Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J London Mar 2024

Plasma Protein Signatures Of Adult Asthma, Gordon J Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B Wyss, Julie D White, Sinjini Sikdar, Jianping Jin, Andrew J Grant, Alison A Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J London

Faculty, Staff and Student Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …


Self-Efficacy To Refuse Sex Mediates The Relationship Between Dating Violence Victimization And Sexual Risk Behavior, Briana Edison, Shristi Bhochhibhoya, Elizabeth R Baumler, Christine M Markham, Melissa F Peskin, Ross Shegog, Susan T Emery, Robert C Addy, Jeff R Temple, Dennis E Reidy Mar 2024

Self-Efficacy To Refuse Sex Mediates The Relationship Between Dating Violence Victimization And Sexual Risk Behavior, Briana Edison, Shristi Bhochhibhoya, Elizabeth R Baumler, Christine M Markham, Melissa F Peskin, Ross Shegog, Susan T Emery, Robert C Addy, Jeff R Temple, Dennis E Reidy

Faculty, Staff and Student Publications

Purpose: While cross-sectional studies have shown that teen dating violence (TDV) victimization is linked to sexual risk behavior (SRB), the pathway between these variables is not well-understood. To address this knowledge gap, we explore the mediating role of self-efficacy to refuse sex in the longitudinal relationship between physical TDV victimization and subsequent SRB among adolescents.

Methods: Self-report data from three prior longitudinal studies were harmonized to create a single aggregated sample of primarily racial and ethnic minority adolescents (N = 4,620; 51.4% Hispanic, 38.5% Black, and 58% female) from 44 schools in the southwest U.S. Participants' physical TDV victimization at …


Lifetime Traumatic Brain Injury And Risk Of Post-Concussive Symptoms In The Millennium Cohort Study, Kalyn C Jannace, Lisa Pompeii, David Gimeno Ruiz De Porras, William Brett Perkison, Jose-Miguel Yamal, Daniel W Trone, Rudolph P Rull Mar 2024

Lifetime Traumatic Brain Injury And Risk Of Post-Concussive Symptoms In The Millennium Cohort Study, Kalyn C Jannace, Lisa Pompeii, David Gimeno Ruiz De Porras, William Brett Perkison, Jose-Miguel Yamal, Daniel W Trone, Rudolph P Rull

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10-60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological …


Genome-Wide Interaction Analysis With Dash Diet Score Identified Novel Loci For Systolic Blood Pressure, Mélanie Guirette, Jessie Lan, Nicola M Mckeown, Michael R Brown, Han Chen, Paul S De Vries, Hyunju Kim, Casey M Rebholz, Alanna C Morrison, Traci M Bartz, Amanda M Fretts, Xiuqing Guo, Rozenn N Lemaitre, Ching-Ti Liu, Raymond Noordam, Renée De Mutsert, Frits R Rosendaal, Carol A Wang, Lawrence J Beilin, Trevor A Mori, Wendy H Oddy, Craig E Pennell, Jin Fang Chai, Clare Whitton, Rob M Van Dam, Jianjun Liu, E Shyong Tai, Xueling Sim, Marian L Neuhouser, Charles Kooperberg, Lesley F Tinker, Nora Franceschini, Tianxiao Huan, Thomas W Winkler, Amy R Bentley, W James Gauderman, Luc Heerkens, Toshiko Tanaka, Jeroen Van Rooij, Patricia B Munroe, Helen R Warren, Trudy Voortman, Honglei Chen, D C Rao, Daniel Levy, Jiantao Ma, Charge Gene-Lifestyle Interactions Working Group Mar 2024

Genome-Wide Interaction Analysis With Dash Diet Score Identified Novel Loci For Systolic Blood Pressure, Mélanie Guirette, Jessie Lan, Nicola M Mckeown, Michael R Brown, Han Chen, Paul S De Vries, Hyunju Kim, Casey M Rebholz, Alanna C Morrison, Traci M Bartz, Amanda M Fretts, Xiuqing Guo, Rozenn N Lemaitre, Ching-Ti Liu, Raymond Noordam, Renée De Mutsert, Frits R Rosendaal, Carol A Wang, Lawrence J Beilin, Trevor A Mori, Wendy H Oddy, Craig E Pennell, Jin Fang Chai, Clare Whitton, Rob M Van Dam, Jianjun Liu, E Shyong Tai, Xueling Sim, Marian L Neuhouser, Charles Kooperberg, Lesley F Tinker, Nora Franceschini, Tianxiao Huan, Thomas W Winkler, Amy R Bentley, W James Gauderman, Luc Heerkens, Toshiko Tanaka, Jeroen Van Rooij, Patricia B Munroe, Helen R Warren, Trudy Voortman, Honglei Chen, D C Rao, Daniel Levy, Jiantao Ma, Charge Gene-Lifestyle Interactions Working Group

Faculty, Staff and Student Publications

Background: The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP.

Methods: We analyzed up to 9 420 585 single nucleotide polymorphisms in up to 127 282 individuals of 6 population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (n=35 660) and UK Biobank (n=91 622) and performed European population-specific and cross-population meta-analyses.

Results: We identified 3 loci in European-specific analyses and an additional 4 loci in cross-population analyses at Pinteraction<5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency, 0.03) and the DASH diet score (P …


Relation Of Prenatal And Postnatal Pm25 Exposure With Cognitive And Motor Function Among Preschool-Aged Children, Kristina W Whitworth, Alison M Rector-Houze, Wei-Jen Chen, Jesus Ibarluzea, Michael Swartz, Elaine Symanski, Carmen Iniguez, Aitana Lertxundi, Antonia Valentin, Llucia González-Safont, Martine Vrijheid, Monica Guxens Mar 2024

Relation Of Prenatal And Postnatal Pm25 Exposure With Cognitive And Motor Function Among Preschool-Aged Children, Kristina W Whitworth, Alison M Rector-Houze, Wei-Jen Chen, Jesus Ibarluzea, Michael Swartz, Elaine Symanski, Carmen Iniguez, Aitana Lertxundi, Antonia Valentin, Llucia González-Safont, Martine Vrijheid, Monica Guxens

Faculty, Staff and Student Publications

The literature informing susceptible periods of exposure on children’s neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM2.5) exposure on children’s cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children’s Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine …


Measurement Bias In Caregiver-Report Of Early Childhood Behavior Problems Across Demographic Factors In An Echo-Wide Diverse Sample, Shuting Zheng, Maxwell Mansolf, Monica Mcgrath, Marie L Churchill, Traci A Bekelman, Patricia A Brennan, Amy E Margolis, Sara S Nozadi, Theresa M Bastain, Amy J Elliott, Kaja Z Lewinn, Julie A Hofheimer, Leslie D Leve, Brandon Rennie, Emily Zimmerman, Carmen A Marable, Cindy T Mcevoy, Chang Liu, Alexis Sullivan, Tracey J Woodruff, Samiran Ghosh, Bennett Leventhal, Assiamira Ferrara, Johnnye Lewis, Somer Bishop Mar 2024

Measurement Bias In Caregiver-Report Of Early Childhood Behavior Problems Across Demographic Factors In An Echo-Wide Diverse Sample, Shuting Zheng, Maxwell Mansolf, Monica Mcgrath, Marie L Churchill, Traci A Bekelman, Patricia A Brennan, Amy E Margolis, Sara S Nozadi, Theresa M Bastain, Amy J Elliott, Kaja Z Lewinn, Julie A Hofheimer, Leslie D Leve, Brandon Rennie, Emily Zimmerman, Carmen A Marable, Cindy T Mcevoy, Chang Liu, Alexis Sullivan, Tracey J Woodruff, Samiran Ghosh, Bennett Leventhal, Assiamira Ferrara, Johnnye Lewis, Somer Bishop

Faculty, Staff and Student Publications

BACKGROUND: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown.

METHODS: Item-level data of CBCL/1.5-5 from a large sample of young children (

RESULTS: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and total Problems. The robust item sets, excluding …


Genetic Drivers Of Heterogeneity In Type 2 Diabetes Pathophysiology, Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E M Melloni, Stavroula Kanoni, Nigel W Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S K Lee, Michael H Preuss, Lauren E Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A Scott, James P Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J Parra, Jin-Fang Chai, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S Nongmaithem, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Jennifer A Brody, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, K Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Tarunveer S Ahluwalia, Sonia S Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A Buchanan, Charles F Burant, Adam S Butterworth, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Torben Jørgensen, Frederick K Kamanu, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Julie A Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D Morris, Filipe A Moura, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Snehal Patil, Pei Pei, Mark A Pereira, Annette Peters, Fraser J Pirie, Hannah G Polikowsky, Bianca Porneala, Gauri Prasad, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M Stilp, Konstantin Strauch, Kent D Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Myriam Fornage, Craig L Hanis, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L R Kardia, Patricia A Peyser, James S Pankow, James C Engert, Amélie Bonnefond, Philippe Froguel, James G Wilson, Wayne H H Sheu, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Dennis O Mook-Kanamori, Tiinamaija Tuomi, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S Rich, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W Bowden, Colin N A Palmer, Jaspal S Kooner, Charles Kooperberg, Simin Liu, Kari E North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y Millwood, Robin G Walters, Kari Stefansson, Emma Ahlqvist, Mark O Goodarzi, Karen L Mohlke, Claudia Langenberg, Christopher A Haiman, Ruth J F Loos, Jose C Florez, Daniel J Rader, Marylyn D Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A Marston, Christian T Ruff, David A Van Heel, Sarah Finer, Joshua C Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C Chambers, Maggie C Y Ng, Xueling Sim, Jennifer E Below, Philip S Tsao, Kyong-Mi Chang, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Cassandra N Spracklen, Josep M Mercader, Michael Boehnke, Jerome I Rotter, Marijana Vujkovic, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini Mar 2024

Genetic Drivers Of Heterogeneity In Type 2 Diabetes Pathophysiology, Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E M Melloni, Stavroula Kanoni, Nigel W Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S K Lee, Michael H Preuss, Lauren E Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A Scott, James P Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J Parra, Jin-Fang Chai, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S Nongmaithem, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Jennifer A Brody, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, K Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Tarunveer S Ahluwalia, Sonia S Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A Buchanan, Charles F Burant, Adam S Butterworth, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Torben Jørgensen, Frederick K Kamanu, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Julie A Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D Morris, Filipe A Moura, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Snehal Patil, Pei Pei, Mark A Pereira, Annette Peters, Fraser J Pirie, Hannah G Polikowsky, Bianca Porneala, Gauri Prasad, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M Stilp, Konstantin Strauch, Kent D Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Myriam Fornage, Craig L Hanis, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L R Kardia, Patricia A Peyser, James S Pankow, James C Engert, Amélie Bonnefond, Philippe Froguel, James G Wilson, Wayne H H Sheu, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Dennis O Mook-Kanamori, Tiinamaija Tuomi, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S Rich, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W Bowden, Colin N A Palmer, Jaspal S Kooner, Charles Kooperberg, Simin Liu, Kari E North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y Millwood, Robin G Walters, Kari Stefansson, Emma Ahlqvist, Mark O Goodarzi, Karen L Mohlke, Claudia Langenberg, Christopher A Haiman, Ruth J F Loos, Jose C Florez, Daniel J Rader, Marylyn D Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A Marston, Christian T Ruff, David A Van Heel, Sarah Finer, Joshua C Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C Chambers, Maggie C Y Ng, Xueling Sim, Jennifer E Below, Philip S Tsao, Kyong-Mi Chang, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Cassandra N Spracklen, Josep M Mercader, Michael Boehnke, Jerome I Rotter, Marijana Vujkovic, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Student Publications

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.


The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer Mar 2024

The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected …


Genome-Wide Gene-Environment Interaction Analyses To Understand The Relationship Between Red Meat And Processed Meat Intake And Colorectal Cancer Risk, Mariana C Stern, Joel Sanchez Mendez, Andre E Kim, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A Harrison, Jeroen R Huyghe, Catherine M Tangen, Polly A Newcomb, Amanda I Phipps, Claire E Thomas, Eric S Kawaguchi, Juan Pablo Lewinger, John L Morrison, David V Conti, Jun Wang, Duncan C Thomas, Elizabeth A Platz, Kala Visvanathan, Temitope O Keku, Christina C Newton, Caroline Y Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel J B Van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K Tsilidis, D Timothy Bishop, Yohannes Adama Melaku, Brigid M Lynch, Daniel D Buchanan, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Andrew J Pellatt, Li Li, Matthew A M Devall, Peter T Campbell, Demetrius Albanes, Stephanie J Weinstein, Sonja I Berndt, Stephen B Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D Joshi, David A Drew, Jessica L Petrick, Andrew T Chan, Marios Giannakis, Ulrike Peters, Li Hsu, W James Gauderman Mar 2024

Genome-Wide Gene-Environment Interaction Analyses To Understand The Relationship Between Red Meat And Processed Meat Intake And Colorectal Cancer Risk, Mariana C Stern, Joel Sanchez Mendez, Andre E Kim, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A Harrison, Jeroen R Huyghe, Catherine M Tangen, Polly A Newcomb, Amanda I Phipps, Claire E Thomas, Eric S Kawaguchi, Juan Pablo Lewinger, John L Morrison, David V Conti, Jun Wang, Duncan C Thomas, Elizabeth A Platz, Kala Visvanathan, Temitope O Keku, Christina C Newton, Caroline Y Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel J B Van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K Tsilidis, D Timothy Bishop, Yohannes Adama Melaku, Brigid M Lynch, Daniel D Buchanan, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Andrew J Pellatt, Li Li, Matthew A M Devall, Peter T Campbell, Demetrius Albanes, Stephanie J Weinstein, Sonja I Berndt, Stephen B Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D Joshi, David A Drew, Jessica L Petrick, Andrew T Chan, Marios Giannakis, Ulrike Peters, Li Hsu, W James Gauderman

Faculty, Staff and Student Publications

Background: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations.

Methods: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan.

Results: Meta-analyses confirmed positive associations between increased consumption of red meat and …


Systematic Evaluation Of Mri-Based Characterization Of Tumor-Associated Vascular Morphology And Hemodynamics Via A Dynamic Digital Phantom, Chengyue Wu, David A Hormuth, Ty Easley, Federico Pineda, Gregory S Karczmar, Thomas E Yankeelov Mar 2024

Systematic Evaluation Of Mri-Based Characterization Of Tumor-Associated Vascular Morphology And Hemodynamics Via A Dynamic Digital Phantom, Chengyue Wu, David A Hormuth, Ty Easley, Federico Pineda, Gregory S Karczmar, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose: Validation of quantitative imaging biomarkers is a challenging task, due to the difficulty in measuring the ground truth of the target biological process. A digital phantom-based framework is established to systematically validate the quantitative characterization of tumor-associated vascular morphology and hemodynamics based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Approach: A digital phantom is employed to provide a ground-truth vascular system within which 45 synthetic tumors are simulated. Morphological analysis is performed on high-spatial resolution DCE-MRI data (spatial/temporal resolution = 30 to 300μm/60s" role="presentation" style="box-sizing: inherit; display: inline-block; line-height: 0; font-size: 18.08px; font-size-adjust: none; overflow-wrap: normal; word-spacing: normal; text-wrap-mode: …


A Scoping Review Of Fair Machine Learning Techniques When Using Real-World Data, Yu Huang, Jingchuan Guo, Wei-Han Chen, Hsin-Yueh Lin, Huilin Tang, Fei Wang, Hua Xu, Jiang Bian Mar 2024

A Scoping Review Of Fair Machine Learning Techniques When Using Real-World Data, Yu Huang, Jingchuan Guo, Wei-Han Chen, Hsin-Yueh Lin, Huilin Tang, Fei Wang, Hua Xu, Jiang Bian

Faculty, Staff and Student Publications

Objective: The integration of artificial intelligence (AI) and machine learning (ML) in health care to aid clinical decisions is widespread. However, as AI and ML take important roles in health care, there are concerns about AI and ML associated fairness and bias. That is, an AI tool may have a disparate impact, with its benefits and drawbacks unevenly distributed across societal strata and subpopulations, potentially exacerbating existing health inequities. Thus, the objectives of this scoping review were to summarize existing literature and identify gaps in the topic of tackling algorithmic bias and optimizing fairness in AI/ML models using real-world data …


Comprehensive Immunogenomic Profiling Of Idh1-/2-Altered Cholangiocarcinoma, Shalini Makawita, Sunyoung Lee, Elisabeth Kong, Lawrence N Kwong, Zeyad Abouelfetouh, Anaemy Danner De Armas, Lianchun Xiao, Karthikeyan Murugesan, Natalie Danziger, Dean Pavlick, Anil Korkut, Jeffrey S Ross, Milind Javle Mar 2024

Comprehensive Immunogenomic Profiling Of Idh1-/2-Altered Cholangiocarcinoma, Shalini Makawita, Sunyoung Lee, Elisabeth Kong, Lawrence N Kwong, Zeyad Abouelfetouh, Anaemy Danner De Armas, Lianchun Xiao, Karthikeyan Murugesan, Natalie Danziger, Dean Pavlick, Anil Korkut, Jeffrey S Ross, Milind Javle

Faculty, Staff and Student Publications

Purpose: Isocitrate dehydrogenase (IDH)1/2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2-mutated iCCA is largely unknown.

Methods: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune cell infiltration, immune marker expression, and T-cell inflammation. Tissue microarray arrays were subjected to multiplex immunohistochemistry and colocalization …


Tongue Electrical Impedance Myography Correlates With Functional, Neurophysiologic, And Clinical Outcome Measures In Long-Term Oropharyngeal Cancer Survivors With And Without Hypoglossal Neuropathy: An Exploratory Study, Nathan J Hansen, Karin Woodman, Sheila Buoy, Shitong Mao, Carly E A Barbon, Stephen Y Lai, C David Fuller, Katherine A Hutcheson, Benjamin Sanchez Mar 2024

Tongue Electrical Impedance Myography Correlates With Functional, Neurophysiologic, And Clinical Outcome Measures In Long-Term Oropharyngeal Cancer Survivors With And Without Hypoglossal Neuropathy: An Exploratory Study, Nathan J Hansen, Karin Woodman, Sheila Buoy, Shitong Mao, Carly E A Barbon, Stephen Y Lai, C David Fuller, Katherine A Hutcheson, Benjamin Sanchez

Faculty, Staff and Student Publications

Background: This pilot study analyzed correlations between tongue electrical impedance myography (EIM), standard tongue electromyography (EMG), and tongue functional measures in N = 4 long-term oropharyngeal cancer (OPC) survivors.

Methods: Patients were screened for a supportive care trial (NCT04151082). Hypoglossal nerve function was evaluated with genioglossus needle EMG, functional measures with the Iowa oral performance instrument (IOPI), and multi-frequency tissue composition with tongue EIM.

Results: Tongue EIM conductivity was higher for patients with EMG-confirmed cranial nerve XII neuropathy than those without (p = 0.005) and in patients with mild versus normal EMG reinnervation ratings (16 kHz EIM: p …


Association Of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use And Patient Outcomes In Advanced Non-Small-Cell Lung Cancer, Jeff Yorio, Katherine T Lofgren, Jessica K Lee, Khaled Tolba, Geoffrey R Oxnard, Alexa B Schrock, Richard S P Huang, Lorraine Brisbin Mar 2024

Association Of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use And Patient Outcomes In Advanced Non-Small-Cell Lung Cancer, Jeff Yorio, Katherine T Lofgren, Jessica K Lee, Khaled Tolba, Geoffrey R Oxnard, Alexa B Schrock, Richard S P Huang, Lorraine Brisbin

Faculty, Staff and Student Publications

PURPOSE: Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions.

METHODS: Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP …


Revisiting Delusion Subtypes In Schizophrenia Based On Their Underlying Structures, Andrew D Van Der Vaart, Yizhou Ma, Joshua Chiappelli, Heather Bruce, Mark D Kvarta, Alia Warner, Xiaoming Du, Bhim M Adhikari, Hemalatha Sampath, Peter Kochunov, L Elliot Hong Mar 2024

Revisiting Delusion Subtypes In Schizophrenia Based On Their Underlying Structures, Andrew D Van Der Vaart, Yizhou Ma, Joshua Chiappelli, Heather Bruce, Mark D Kvarta, Alia Warner, Xiaoming Du, Bhim M Adhikari, Hemalatha Sampath, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

A clear understanding of the pathophysiology of schizophrenia and related spectrum disorders has been limited by clinical heterogeneity. We investigated whether relative severity and predominance of one or more delusion subtypes might yield clinically differentiable patient profiles. Patients (N = 286) with schizophrenia spectrum disorders (SSD) completed the 21-item Peters et al. Delusions Inventory (PDI-21). We performed factor analysis followed by k-means clustering to identify delusion factors and patient subtypes. Patients were further assessed via the Brief Psychiatric Rating Scale, Brief Negative Symptom Scale, Digit Symbol and Digit Substitution tasks, use of cannabis and tobacco, and stressful life events. The …


Corrigendum To 'Molecular Identity Changes Of Tumor-Associated Macrophages And Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Mouse Glioblastoma Model' [Ultrasound In Med & Biol 49 (2023) 1082-1090], Yanrong Zhang, Jing Wang, Sara Natasha Ghobadi, Haiyan Zhou, Ai Huang, Marco Gerosa, Qingyi Hou, Olivier Keunen, Anna Golebiewska, Frezghi G Habte, Gerald A Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark Mar 2024

Corrigendum To 'Molecular Identity Changes Of Tumor-Associated Macrophages And Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Mouse Glioblastoma Model' [Ultrasound In Med & Biol 49 (2023) 1082-1090], Yanrong Zhang, Jing Wang, Sara Natasha Ghobadi, Haiyan Zhou, Ai Huang, Marco Gerosa, Qingyi Hou, Olivier Keunen, Anna Golebiewska, Frezghi G Habte, Gerald A Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark

Faculty, Staff and Student Publications

No abstract provided.


Decreasing Polypharmacy In Older Adults With Cancer: A Pilot Cluster-Randomized Trial Protocol, Erika Ramsdale, Mostafa Mohamed, Holly M Holmes, Lisa Zubkoff, Jessica Bauer, Sally A Norton, Supriya Mohile Mar 2024

Decreasing Polypharmacy In Older Adults With Cancer: A Pilot Cluster-Randomized Trial Protocol, Erika Ramsdale, Mostafa Mohamed, Holly M Holmes, Lisa Zubkoff, Jessica Bauer, Sally A Norton, Supriya Mohile

Faculty, Staff and Student Publications

Introduction: Polypharmacy is prevalent in older adults with cancer and associated with multiple adverse outcomes. A single-site, cluster-randomized clinical trial will enroll older adults with cancer and polypharmacy starting chemotherapy and will assess the effectiveness and feasibility of deprescribing interventions by comparing two arms: a pharmacist-led deprescribing intervention and a patient educational brochure.

Materials and methods: The study will be conducted in two phases. In phase I, focus groups and semi-structured individual interviews will guide adaptation of deprescribing interventions for the oncology clinic (phase Ia), and eight patients will undergo the pharmacist-led deprescribing intervention with iterative adaptations (phase Ib). In …


Obstetric Racism, Education, And Racial Concordance, Terri L Major-Kincade Mar 2024

Obstetric Racism, Education, And Racial Concordance, Terri L Major-Kincade

Faculty, Staff and Student Publications

The United States holds the distinction of being the developed country with the worst perinatal outcomes despite spending the most per capita on health care. Black women are three to four times more likely than White women to experience adverse birth outcomes. These outcomes persist despite access to prenatal care, insurance, and college education. A long overdue racial reckoning has arrived, beginning with acknowledging the fallacy of race-based medicine and the role of enduring systemic racism as foundational to obstetric racism in the reproductive lives of Black women. Centering voices of Black women and honoring their lived experiences are essential …