Digital Commons Network^™

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

Research Priorities For Childhood Apraxia Of Speech: A Long View, Patricia Mccabe, Molly Beiting, Elaine R Hitchcock, Edwin Maas, Amy Meredith, Angela T Morgan, Nancy L Potter, Jonathan L Preston, Laura Moorer, Pooja Aggarwal, Kirrie Ballard, Laura Baskall Smith, Nicole F Caballero, Kathryn Cabbage, Julie Case, Susan Caspari, Karen V Chenausky, Shina Cook, Ewa Grzelak, Maryane Gomez, Aubrie Hagopian, Chantelle Highman, Anne Hodits, Jenya Iuzzini-Seigel, Jillian Levos-Carlson, Barbara A Lewis, Patricia Mayro, Jyutika Mehta, Gabrielle Miller, Kimberly D Mory, Elizabeth Murray, Megan S Overby, Lucia Pasquel-Lefebvre, Derrick Peavy, Caitlin V Raaz, Brooke Rea, Denise Santos Ford, Lynn Smith, Michelle T. Swartz, Melissa Taberski, Hayo Terband, Donna C Thomas, Hannah Valentine, Mirjam Van Tellingen, Shelley Velleman, Emily Wang, Sarah White, Eddy C H Wong, Maria I Grigos

Department of Speech-Language Pathology Faculty Papers

This article introduces the Journal of Speech, Language, and Hearing Research Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium. The field of childhood apraxia of speech (CAS) has developed significantly in the past 15 years, with key improvements in understanding of basic biology including genetics, neuroscience, and computational modelling; development of diagnostic tools and methods; diversity of evidence-based interventions with increasingly rigorous experimental designs; and understanding of impacts beyond impairment-level measures. Papers in this special issue not only review and synthesize the some of the substantial progress to date but also present novel findings addressing critical research …

Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang

Faculty, Staff and Student Publications

BACKGROUND: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions.

METHODS: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, …

Skin In The Game: A Review Of Single-Cell And Spatial Transcriptomics In Dermatological Research, Samuel Schepps, Jonathan Xu, Henry Yang, Jenna Mandel, Jaanvi Mehta, Julianna Tolotta, Nicole Baker, Volkan Tekmen, Neda Nikbakht, Paolo Fortina, Ignacia Fuentes, Bonnie Lafleur, Raymond J Cho, Andrew P South

Staff and Researcher Publications

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, …

Stimulation Of An Entorhinal-Hippocampal Extinction Circuit Facilitates Fear Extinction In A Post-Traumatic Stress Disorder Model, Ze-Jie Lin, Xue Gu, Wan-Kun Gong, Mo Wang, Yan-Jiao Wu, Qi Wang, Xin-Rong Wu, Xin-Yu Zhao, Michael X Zhu, Lu-Yang Wang, Quanying Liu, Ti-Fei Yuan, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Effective psychotherapy of post-traumatic stress disorder (PTSD) remains challenging owing to the fragile nature of fear extinction, for which the ventral hippocampal CA1 (vCA1) region is considered as a central hub. However, neither the core pathway nor the cellular mechanisms involved in implementing extinction are known. Here, we unveil a direct pathway, where layer 2a fan cells in the lateral entorhinal cortex (LEC) target parvalbumin-expressing interneurons (PV-INs) in the vCA1 region to propel low-gamma-band synchronization of the LEC-vCA1 activity during extinction learning. Bidirectional manipulations of either hippocampal PV-INs or LEC fan cells sufficed for fear extinction. Gamma entrainment of vCA1 …

In Vivo Crispr Screens Identify Mga As An Immunotherapy Target In Triple-Negative Breast Cancer, Xu Feng, Chang Yang, Yuanjian Huang, Dan Su, Chao Wang, Lori Lyn Wilson, Ling Yin, Mengfan Tang, Siting Li, Zhen Chen, Dandan Zhu, Shimin Wang, Shengzhe Zhang, Jie Zhang, Huimin Zhang, Litong Nie, Min Huang, Jae-Il Park, Traver Hart, Dadi Jiang, Kuirong Jiang, Junjie Chen

Faculty, Staff and Student Publications

Understanding the mechanisms underlying immune evasion is crucial for developing novel anticancer modalities. To systematically uncover tumor-intrinsic genetic modulators involved in immune escape in tumor microenvironment, we performed genome-scale in vivo CRISPR screens in two syngeneic models and later expanded up to seven syngeneic models with a focused validation library. These data help us better understand tumor immune evasion and pave the way for developing effective therapeutics. Importantly, we uncovered that Mga depletion elicited an antitumor immune response and inhibited tumor growth in triple-negative breast cancer. Our findings suggest that Mga may play a role in modulating the tumor immune …

The Centrosomal Protein Fgfr1op Controls Myosin Function In Murine Intestinal Epithelial Cells, Tihana Trsan, Vincent Peng, Takahiro E Ohara, Wandy L Beatty, Raki Sudan, Praveen Krishnamoorthy, Patrick Fernandes Rodrigues, Jose L Fachi, Gary Grajales-Reyes, Natalia Jaeger, James A J Fitzpatrick, Marina Cella, Susan Gilfillan, Marco Colonna, Et Al.

2020-Current year OA Pubs

Recent advances in human genetics have shed light on the genetic factors contributing to inflammatory diseases, particularly Crohn's disease (CD), a prominent form of inflammatory bowel disease. Certain risk genes associated with CD directly influence cytokine biology and cell-specific communication networks. Current CD therapies primarily rely on anti-inflammatory drugs, which are inconsistently effective and lack strategies for promoting epithelial restoration and mucosal balance. To understand CD's underlying mechanisms, we investigated the link between CD and the FGFR1OP gene, which encodes a centrosome protein. FGFR1OP deletion in mouse intestinal epithelial cells disrupted crypt architecture, resulting in crypt loss, inflammation, and fatality. …

Metadegron: Multimodal Feature-Integrated Protein Language Model For Predicting E3 Ligase Targeted Degrons, Mengqiu Zheng, Shaofeng Lin, Kunqi Chen, Ruifeng Hu, Liming Wang, Zhongming Zhao, Haodong Xu

Faculty, Staff and Student Publications

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive …

Examining Management And Employees' Perceptions Of Occupational Heat Exposure And The Effectiveness Of A Heat Stress Prevention Intervention On Safety And Well-Being Among Natural Gas Construction Workers: A Qualitative Field-Based Study, Muinat Abolore Idris, Christine Markham, Kristina D Mena, William B Perkison

Faculty, Staff and Student Publications

BACKGROUND: Numerous risk factors have been identified as significantly influencing outdoor workers' risk for heat stress and heat-related conditions, impacting their health, well-being, and productivity. However, the specific effects of these factors on construction workers' safety, health, and well-being remain under-researched. With climate change increasing temperatures, assessing heat stress among construction workers is imperative.

OBJECTIVE: To identify the barriers and facilitators influencing the safety of natural gas construction workers and evaluate an implemented heat stress intervention.

METHODS: In the summer of 2023, two semi-structured interviews and six focus groups were conducted with twenty-one stakeholders at a Texas natural gas construction …

Cyp1b1-Rmdn2 Alzheimer's Disease Endophenotype Locus Identified For Cerebral Tau Pet, Kwangsik Nho, Muhammad Ali, Tammie Benzinger, Carlos Cruchaga, Diana Hobbs, Et Al.

2020-Current year OA Pubs

Determining the genetic architecture of Alzheimer's disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. …

Oxa-Iboga Alkaloids Lack Cardiac Risk And Disrupt Opioid Use In Animal Models, Václav Havel, Amanda Hunkele, Rohini S Ople, Susruta Majumdar, Et Al.

2020-Current year OA Pubs

Ibogaine and its main metabolite noribogaine provide important molecular prototypes for markedly different treatment of substance use disorders and co-morbid mental health illnesses. However, these compounds present a cardiac safety risk and a highly complex molecular mechanism. We introduce a class of iboga alkaloids - termed oxa-iboga - defined as benzofuran-containing iboga analogs and created via structural editing of the iboga skeleton. The oxa-iboga compounds lack the proarrhythmic adverse effects of ibogaine and noribogaine in primary human cardiomyocytes and show superior efficacy in animal models of opioid use disorder in male rats. They act as potent kappa opioid receptor agonists …

Paediatric Mass Casualty Response Through The Lens Of Functional Resonance Analytical Methodology- Lessons Learned., R J Mackinnon, D Slater, R Jenner, T Stenfors, Christopher S. Kennedy, K P Härenstam

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Mass Casualty Incidents are rare but can significantly stress healthcare systems. Functional Resonance Analytical Methodology (FRAM) is a systematic approach to model and explore how complex systems adapt to variations and to understand resilient properties in the face of perturbations. The aim of this study was to use FRAM to create a model of a paediatric trauma system during the initial response to the Manchester Arena Attack to provide resilience-based insights for the management of future Mass Casualty Incidents (MCI).

METHODS: Qualitative interviews in the immediate aftermath of a terrorist bombing, were followed up with further in-depth probing of …

Variant Surface Protein Gp60 Contributes To Host Infectivity Of Cryptosporidium Parvum, Muxiao Li, Fuxian Yang, Tianyi Hou, Xiaoqing Gong, Na Li, L David Sibley, Yaoyu Feng, Lihua Xiao, Yaqiong Guo

2020-Current year OA Pubs

Biological studies of the determinants of Cryptosporidium infectivity are lacking despite the fact that cryptosporidiosis is a major public health problem. Recently, the 60-kDa glycoprotein (GP60) has received attention because of its high sequence polymorphism and association with host infectivity of isolates and protection against reinfection. However, studies of GP60 function have been hampered by its heavy O-linked glycosylation. Here, we used advanced genetic tools to investigate the processing, fate, and function of GP60. Endogenous gene tagging showed that the GP60 cleavage products, GP40 and GP15, are both highly expressed on the surface of sporozoites, merozoites and male gametes. During …

Diagnostic Error In Mental Health: A Review, Andrea Bradford, Ashley N D Meyer, Sundas Khan, Traber D Giardina, Hardeep Singh

Faculty, Staff and Students Publications

Diagnostic errors are associated with patient harm and suboptimal outcomes. Despite national scientific efforts to advance definition, measurement and interventions for diagnostic error, diagnosis in mental health is not well represented in this ongoing work. We aimed to summarise the current state of research on diagnostic errors in mental health and identify opportunities to align future research with the emerging science of diagnostic safety. We review conceptual considerations for defining and measuring diagnostic error, the application of these concepts to mental health settings, and the methods and subject matter focus of recent studies of diagnostic error in mental health. We …

Generalized Encoding Of The Relative Subjective Value Of Cognitive Effort In The Dorsal Acc, Jennifer L Crawford, Rachel E Brough, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a …

Design Of A Tool Capable Of Assessing Environmental Sociocultural Physical Factors Influencing Women's Decisions On When And Where To Toilet Within Real-World Settings: Protocol For The Build And Usability Testing Of A Mobile App For Use By Community-Dwelling Women, Janis M Miller, Jean F Wyman, Lawrence An, Haitao Chu, Cynthia S Fok, Missy Lavender, Cora Elizabeth Lewis, Alayne D Markland, Leslie M Rickey, Ying Sheng, Siobhan Sutcliffe, Lisa Kane Low, Elizabeth R Mueller

2020-Current year OA Pubs

BACKGROUND: Although surveys and apps are available for women to report urination and bladder symptoms, they do not include their decisions regarding toileting. Real-world factors can interfere with toileting decisions, which may then influence bladder health. This premise lacks data per want of a robust data collection tool.

OBJECTIVE: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium engaged a transdisciplinary team to build and test WhereIGo, a mobile data collection app for Android and iOS. The design goal was a comprehensive reporting system for capturing environmental, sociocultural, and physical factors that influence women's decisions for toileting. Aims include …

Fueling The Heart: What Are The Optimal Dietary Strategies In Heart Failure?, Anahita Ataran, Alexander Pompian, Hamidreza Hajirezaei, Rehman Lodhi, Ali Javaheri

2020-Current year OA Pubs

OBJECTIVES: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF.

METHODS: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression.

RESULTS: Many of these strategies remain under clinical and basic …

Complex Trait Associations In Rare Diseases And Impacts On Mendelian Variant Interpretation., Craig Smail, Bing Ge, Marissa R. Keever-Keigher, Carl F. Schreck, Warren A. Cheung, Jeffrey J. Johnston, Cassandra Barrett, Genomic Answers For Kids Consortium, Keith Feldman, Ana S A Cohen, Emily G. Farrow, Isabelle Thiffault, Elin Grundberg, Tomi Pastinen

Manuscripts, Articles, Book Chapters and Other Papers

Emerging evidence implicates common genetic variation - aggregated into polygenic scores (PGS) - in the onset and phenotypic presentation of rare diseases. Here, we comprehensively map individual polygenic liability for 1102 open-source PGS in a cohort of 3059 probands enrolled in the Genomic Answers for Kids (GA4K) rare disease study, revealing widespread associations between rare disease phenotypes and PGSs for common complex diseases and traits, blood protein levels, and brain and other organ morphological measurements. Using this resource, we demonstrate increased polygenic liability in probands with an inherited candidate disease variant (VUS) compared to unaffected carrier parents. Further, we show …

Rethinking Health Systems Responsiveness In Low- And Middle-Income Countries: Validation Study, Meesha Iqbal, Cecilia Ganduglia Cazaban, Robert Morgan, Cici Bauer, Sameen Siddiqi

Faculty, Staff and Student Publications

BACKGROUND: Health systems responsiveness (HSR) is the ability of systems to respond to legitimate non-health expectations of the population. The concept of HSR by the World Health Organization (WHO) includes respect for dignity, individual autonomy, confidentiality, prompt attention to care, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. The WHO tool is applied globally to assess HSR in low, middle, and high-income countries.

OBJECTIVE: We have revised the conceptual framework of HSR following a rigorous systematic review and made it specific for low- and middle-income countries (L&MICs). This study is designed to …

Adaptation Of The Socioecological Model To Address Disparities In Engagement Of Black Men In Prostate Cancer Genetic Testing, Amy Leader, Timothy Rebbeck, William Oh, Alpa Patel, Eric Winer, Leeann Bailey, Leonard Gomella, Crystal Lumpkins, Isla Garraway, Lisa Aiello, Monica Baskin, Heather H Cheng, Kathleen Cooney, Amanda Ganzak, Daniel George, Susan Halabi, Feighanne Hathaway, Claire Healy, Joseph W Kim, Michael Leapman, Stacy Loeb, Kara Maxwell, Christopher Mcnair, Todd Morgan, Breanne Prindeville, Howard R Soule, Whitney Steward, Sakinah Suttiratana, Mary-Ellen Taplin, Kosj Yamoah, Thierry Fortune, Kris Bennett, Joshua Blanding-Godbolt, Laura Gross, Veda Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT.

METHODS: Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa …

Development Of A Maturity Assessment Tool To Evaluate And Strengthen National Immunization Technical Advisory Groups (Nitags), Eliza Dryer, Abigail Shefer, Shalini Desai, Lance Rodewald, Magdalena Bastías, Nathalie El Omeiri, Sidy Ndiaye, Kori Cook, Louise Henaff, Erin Kennedy

Staff and Researcher Publications

As dozens of new National Immunization Technical Advisory Groups (NITAGs) were established worldwide in the past decade, and as existing NITAGs continued to play an important role in vaccine policy, global NITAG partners recognized a need for a standardized assessment tool to evaluate and strengthen their functions. This article describes the development of the NITAG Maturity Assessment Tool (NMAT), a stepwise evaluation tool that assesses NITAGs on seven key indicators of structure and process. A draft tool was developed through an iterative, consensus-based process with an expert working group before it was piloted with an economically and geographically diverse convenience …

Impact Of An Online Decision Support Tool For Ductal Carcinoma In Situ (Dcis) Using A Pre-Post Design (Aft-25), Elissa Ozanne, Kellyn Maves, Angela Tramontano, Thomas Lynch, Alastair Thompson, Ann Partridge, Elizabeth Frank, Deborah Collyar, Desiree Basila, Donna Pinto, Terry Hyslop, Marc Ryser, Shoshana Rosenberg, E. Shelley Hwang, Rinaa Punglia

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: The heterogeneous biology of ductal carcinoma in situ (DCIS), as well as the variable outcomes, in the setting of numerous treatment options have led to prognostic uncertainty. Consequently, making treatment decisions is challenging and necessitates involved communication between patient and provider about the risks and benefits. We developed and investigated an interactive decision support tool (DST) designed to improve communication of treatment options and related long-term risks for individuals diagnosed with DCIS.

FINDINGS: The DST was developed for use by individuals aged > 40 years with DCIS and is based on a disease simulation model that integrates empirical data and …

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Loss Of P53 And Smad4 Induces Adenosquamous Subtype Pancreatic Cancer In The Absence Of An Oncogenic Kras Mutation, Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53

A Qualitative Exploration Of Disseminating Research Findings Among Public Health Researchers In China, Yiluan Hu, Xuejun Yin, Yachen Wang, Enying Gong, Xin Xin, Jing Liu, Xia Liu, Ruitai Shao, Juan Zhang, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Research dissemination is essential to accelerate the translating of evidence into practice. Little is known about dissemination among Chinese public health researchers. This study aimed to explore the understanding and practices of disseminating research findings and to identify barriers and facilitators that influence dissemination activities to non-research audiences.

METHODS: This study deployed an exploratory qualitative design with purposive and snowball sampling. One focus group with 5 participants and 12 in-depth interviews were conducted with participants working in diverse fields from universities (n = 10), the National Chinese Center for Disease Control and Prevention (n = 4), the Chinese National …

Hif-2Α-Dependent Induction Of Mir-29a Restrains Th1 Activity During T Cell Dependent Colitis, Agnieszka K Czopik, Eóin N Mcnamee, Victoria Vaughn, Xiangsheng Huang, In Hyuk Bang, Trent Clark, Yanyu Wang, Wei Ruan, Tom Nguyen, Joanne C Masterson, Eunyoung Tak, Sandra Frank, Colm B Collins, Howard Li, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Mark E Gerich, Glenn T Furuta, Xiaoyi Yuan, Anil K Sood, Edwin F De Zoeten, Holger K Eltzschig

Faculty, Staff and Student Publications

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4+ T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target …

Impact And Characterization Of Serial Structural Variations Across Humans And Great Apes, Wolfram Höps, Tobias Rausch, Michael Jendrusch, Jan O Korbel, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series of mutations, a phenomenon we refer to as serial SV (sSV), remain underexplored, posing a challenge for SV discovery. Here, we present NAHRwhals ( https://github.com/WHops/NAHRwhals ), a method to infer repeat-mediated series of SVs in long-read genomic assemblies. Applying NAHRwhals to haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci of various length and complexity. These sSVs explain otherwise cryptic variation in medically relevant regions such as the TPSAB1 gene, 8p23.1, 22q11 and Sotos syndrome regions. Comparisons …

Use Of Guideline-Recommended Heart Failure Drugs In High-, Middle-, And Low-Income Countries: A Systematic Review And Meta-Analysis, Gautam Satheesh, Rupasvi Dhurjati, Laura Alston, Fisaha Tesfay, Rashmi Pant, Ehete Bahiru, Claudia Bambs, Anubha Agarwal, Sanne A E Peters, Abdul Salam, Isabelle Johansson

2020-Current year OA Pubs

Optimal use of guideline-directed medical therapy (GDMT) can prevent hospitalization and mortality among patients with heart failure (HF). We aimed to assess the prevalence of GDMT use for HF across geographic regions and country-income levels. We systematically reviewed observational studies (published between January 2010 and October 2020) involving patients with HF with reduced ejection fraction. We conducted random-effects meta-analyses to obtain summary estimates. We included 334 studies comprising 1,507,849 patients (31% female). The majority (82%) of studies were from high-income countries, with Europe (45%) and the Americas (33%) being the most represented regions, and Africa (1%) being the least. Overall …

Context-Aware Single-Cell Multiomics Approach Identifies Cell-Type-Specific Lung Cancer Susceptibility Genes, Erping Long, Jinhu Yin, Ju Hye Shin, Yuyan Li, Bolun Li, Alexander Kane, Harsh Patel, Xinti Sun, Cong Wang, Thong Luong, Jun Xia, Younghun Han, Jinyoung Byun, Tongwu Zhang, Wei Zhao, Maria Teresa Landi, Nathaniel Rothman, Qing Lan, Yoon Soo Chang, Fulong Yu, Christopher I Amos, Jianxin Shi, Jin Gu Lee, Eun Young Kim, Jiyeon Choi

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. …

Prenatal Environment Is Associated With The Pace Of Cortical Network Development Over The First Three Years Of Life, Ursula A Tooley, Aidan Latham, Jeanette K Kenley, Dimitrios Alexopoulos, Tara A Smyser, Ashley N Nielsen, Lisa Gorham, Barbara B Warner, Joshua S Shimony, Jeffrey J Neil, Joan L Luby, Deanna M Barch, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Environmental influences on brain structure and function during early development have been well-characterized, but whether early environments are associated with the pace of brain development is not clear. In pre-registered analyses, we use flexible non-linear models to test the theory that prenatal disadvantage is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal disadvantage was assessed using a latent factor of socioeconomic disadvantage that included measures of mother's income-to-needs ratio, educational attainment, area deprivation index, insurance status, and nutrition. We find that prenatal disadvantage is associated with developmental increases in …