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Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll Dec 2024

Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which …


Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet Dec 2024

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …


Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators Dec 2024

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …


Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen Dec 2024

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …


Langerhans Cell Histiocytosis In Children Born After Assisted Reproductive Technology, Carrie L Williams, Kathryn J Bunch, Charles Stiller, Michael F G Murphy, Beverley J Botting, Melanie C Davies, Barbara Luke, Philip J Lupo, Alastair G Sutcliffe Dec 2024

Langerhans Cell Histiocytosis In Children Born After Assisted Reproductive Technology, Carrie L Williams, Kathryn J Bunch, Charles Stiller, Michael F G Murphy, Beverley J Botting, Melanie C Davies, Barbara Luke, Philip J Lupo, Alastair G Sutcliffe

Center for Medical Ethics and Health Policy Staff Publications

Research question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?

Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence …


Modification Of A Parent-Report Sleep Scale For Individuals With Cdkl5 Deficiency Disorder: A Psychometric Study, Jacinta M Saldaris, Scott Demarest, Peter Jacoby, Heather E Olson, Kiran Maski, Elia Pestana-Knight, Dana Price, Rajsekar Rajaraman, Bernhard Suter, Judith Weisenberg, Helen Leonard, Eric D Marsh, Tim A Benke, Jenny Downs Dec 2024

Modification Of A Parent-Report Sleep Scale For Individuals With Cdkl5 Deficiency Disorder: A Psychometric Study, Jacinta M Saldaris, Scott Demarest, Peter Jacoby, Heather E Olson, Kiran Maski, Elia Pestana-Knight, Dana Price, Rajsekar Rajaraman, Bernhard Suter, Judith Weisenberg, Helen Leonard, Eric D Marsh, Tim A Benke, Jenny Downs

Faculty, Staff and Students Publications

Study objectives: Sleep difficulties are common in CDKL5 deficiency disorder, a developmental and epileptic encephalopathy. This study evaluated the factor structure of the Disorders of Initiating and Maintaining Sleep (DIMS), Disorders of Excessive Somnolence (DOES), and Sleep Breathing Disorders domains of the Sleep Disturbance Scale for Children for CDKL5 deficiency disorder.

Methods: A cross-sectional psychometric study design was used. Data were collected for 125 individuals aged 3 years or older who attended a United States Centers of Excellence clinic or registered with the International CDKL5 Disorder Database.

Results: The median age was 10.3 years (range 3.2-40.7 years) and 105 (84%) …


Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin P Zachariah, Tavleen Singh, Shannon Collinson, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson Dec 2024

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin P Zachariah, Tavleen Singh, Shannon Collinson, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson

Faculty, Staff and Students Publications

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition.

Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition …


Effects Of Trauma Exposure And Posttraumatic Stress Disorder On Perceived Social Support In Youth: A Longitudinal Investigation, Erin Logue, John Leri, Jeffrey D Shahidullah, Caitlin M Pinciotti, Paul J Rathouz, Josh M Cisler, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff Dec 2024

Effects Of Trauma Exposure And Posttraumatic Stress Disorder On Perceived Social Support In Youth: A Longitudinal Investigation, Erin Logue, John Leri, Jeffrey D Shahidullah, Caitlin M Pinciotti, Paul J Rathouz, Josh M Cisler, D Jeffrey Newport, Karen Dineen Wagner, Charles B Nemeroff

Faculty, Staff and Students Publications

The aim of this study was to examine relationships among trauma burden, post-traumatic stress disorder, and perceived social support in a large, diverse group of trauma-exposed children and adolescents followed longitudinally. Specifically, we tested the social erosion hypothesis (i.e., mental health challenges negatively affect the quality of social relationships and contribute to reduced social support over time) using a sample of 1,829 trauma-exposed youth (aged 8-21) recruited through the multi-site Texas Childhood Trauma Research Network. Youth who reported more trauma burden (i.e., a greater number of traumas) perceived significantly lower levels of social support from family and peers, and those …


Temporal Trends In Mortality Related To Stroke And Atrial Fibrillation In The United States: A 21-Year Retrospective Analysis Of Cdc-Wonder Database, Owais Ahmad, Hanzala Ahmed Farooqi, Isra Ahmed, Adeena Jamil, Rayyan Nabi, Irfan Ullah, Abdul Wali Khan, Raheel Ahmed, Mahboob Alam, Bernardo Cortese, Mamas A Mamas Dec 2024

Temporal Trends In Mortality Related To Stroke And Atrial Fibrillation In The United States: A 21-Year Retrospective Analysis Of Cdc-Wonder Database, Owais Ahmad, Hanzala Ahmed Farooqi, Isra Ahmed, Adeena Jamil, Rayyan Nabi, Irfan Ullah, Abdul Wali Khan, Raheel Ahmed, Mahboob Alam, Bernardo Cortese, Mamas A Mamas

Faculty, Staff and Students Publications

Aims: Atrial Fibrillation (AF) is one of the most strongly associated risk factors for stroke. Our study aims to analyze changes in mortality from 1999 to 2020 in patients with AF and stroke.

Methods: Using the Centre for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER), we retrospectively analyzed annual age-adjusted mortality rates (AAMR) per million from 1999 to 2020 in stroke patients with AF. Temporal trends were analyzed, and Annual Percentage Change (APC) was calculated using the JoinPoint regression model across variations in demographics (sex, race) and regional subgroups.

Results: Around 490 000 deaths were reported …


Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin Dec 2024

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …


Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas Dec 2024

Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas

Faculty, Staff and Students Publications

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and …


Infant-Derived Human Nasal Organoids Exhibit Relatively Increased Susceptibility, Epithelial Responses, And Cytotoxicity During Rsv Infection, Gina M Aloisio, Divya Nagaraj, Ashley M Murray, Emily M Schultz, Trevor Mcbride, Letisha Aideyan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Anubama Rajan, Amal Kambal, Hannah L Johnson, Elina Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula Dec 2024

Infant-Derived Human Nasal Organoids Exhibit Relatively Increased Susceptibility, Epithelial Responses, And Cytotoxicity During Rsv Infection, Gina M Aloisio, Divya Nagaraj, Ashley M Murray, Emily M Schultz, Trevor Mcbride, Letisha Aideyan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Anubama Rajan, Amal Kambal, Hannah L Johnson, Elina Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

Background: Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.

Methods: We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.

Results: Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. …


Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily Dec 2024

Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily

Faculty, Staff and Students Publications

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was …


The Association Between Care Integration And Care Quality, Adam Scherling, Anna D Sinaiko, Sara J Singer Dec 2024

The Association Between Care Integration And Care Quality, Adam Scherling, Anna D Sinaiko, Sara J Singer

Faculty, Staff and Student Publications

Objective: The study aims to analyze the relationship between care integration and care quality, and to examine if the relationship varies by patient risk.

Data sources and study setting: The key independent variables used validated measures derived from a provider survey of functional (i.e., administrative and clinical systems) and social (i.e., patient integration, professional cooperation, professional coordination) integration. Survey responses represented data from a stratified sample of 59 practice sites from 17 health systems. Dependent variables included three quality measures constructed from patient-level Medicare data: colorectal cancer screening among patients at risk, patient-level 30-day readmission, and a practice-level Healthcare Effectiveness …


Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Haoran Xue, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu Dec 2024

Identification Of Proteins Associated With Type 2 Diabetes Risk In Diverse Racial And Ethnic Populations, Haoran Xue, Peter Durda, Russell P Tracy, Yongmei Liu, W Craig Johnson, Kent D Taylor, Ani W Manichaikul, Mark O Goodarzi, Robert E Gerszten, Clary B Clish, Yii-Der Ida Chen, Heather Highland, Christopher A Haiman, Christopher R Gignoux, Leslie Lange, David V Conti, Laura M Raffield, Lynne Wilkens, Kari E North, Kristin L Young, Ruth J Loos, Steve Buyske, Tara Matise, Ulrike Peters, Charles Kooperberg, Alexander P Reiner, Bing Yu, Eric Boerwinkle, Quan Sun, Mary R Rooney, Justin B Echouffo-Tcheugui, Martha L Daviglus, Qibin Qi, Nicholas Mancuso, Changwei Li, Youping Deng, Alisa Manning, James B Meigs, Stephen S Rich, Jerome I Rotter, Lang Wu

Faculty, Staff and Student Publications

Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs. The models were …


Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Beth A Dombroski, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso Dec 2024

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Beth A Dombroski, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …


Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans Dec 2024

Economic Disadvantage During Childhood, Obesity, And Diabetes Across Three Birth Cohorts Of Older Mexicans

Faculty, Staff and Student Publications

OBJECTIVES: Diabetes prevalence has increased markedly in Mexico. We examined the individual and joint contributions of economic disadvantage during childhood (EDDC) and elevated body weight on diabetes prevalence in 3 cohorts of Mexican adults.

METHODS: Data on those 60-69 years old from the 1930-1939, 1940-1949, and 1950-1959 birth cohorts in Waves 1 (2001), 3 (2012), and 5 (2018) of the Mexican Health and Aging Study were used. EDDC was defined as the absence of a toilet in the household before age 10. Body mass status was defined using self-reported perceived body image at age 50. Diabetes was based on respondent …


Whole-Of-School Physical Activity Promotion: Findings From Elementary Schools In The United States, Kempson Onadeko, Laura F Defina, Timothy J Walker Dec 2024

Whole-Of-School Physical Activity Promotion: Findings From Elementary Schools In The United States, Kempson Onadeko, Laura F Defina, Timothy J Walker

Faculty, Staff and Student Publications

INTRODUCTION: Schools can support students' participation in physical activity by offering opportunities consistent with a Whole-of-School (WOS) approach; however, the extent to which physical activity opportunities are provided and how school-level characteristics associate with their use remains unclear. This study examined how elementary schools' use a WOS approach to promote physical activity, as well as associations between school-level characteristics and physical activity opportunities provided.

METHODS: Survey data was collected from 162 elementary schools participating in the NFL PLAY 60 FitnessGram Project during the 2022-2023 school year. A WOS index (ranging from 0 to 12) was created from responses by school …


Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Rebecca Bernal, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal Dec 2024

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Rebecca Bernal, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …


Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Adrienne Tin, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi Dec 2024

Prediagnostic Amino Acid Metabolites And Risk Of Gout, Accounting For Serum Urate: Prospective Cohort Study And Mendelian Randomization, Adrienne Tin, Oana Zeleznik, A Heather Eliassen, Gary C Curhan, Hang-Korng Ea, Matthew Nayor, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

Objective: Our objective was to prospectively investigate prediagnostic population-based metabolome for risk of hospitalized gout (ie, most accurate, severe, and costly cases), accounting for serum urate.

Methods: We conducted prediagnostic metabolome-wide analyses among 249,677 UK Biobank participants with nuclear magnetic resonance metabolomic profiling (N = 168 metabolites, including eight amino acids) from baseline blood samples (2006-2010) without a history of gout. We calculated multivariable hazard ratios (HRs) for hospitalized incident gout, before and after adjusting for serum urate levels; we included patients with nonhospitalized incident gout in a sensitivity analysis. Potential causal effects were evaluated with two-sample Mendelian randomization.

Results: …


Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Soyoung Kwon Dec 2024

Covid-19 Risk Assessment Among Vulnerable Small Business Owners In El Paso County, Texas, Soyoung Kwon

Faculty, Staff and Student Publications

Background: Our objective was to deliver actionable, worksite-specific COVID-19 risk assessments and mitigation strategies tailored to vulnerable workers in one of the highest-risk areas in the US.

Methods: Four trained, bilingual (English/Spanish) community health workers (CHWs) recruited small businesses (ie, ≤20 employees) across various industries and executed novel on-site infectious disease risk assessment surveys of at least one employer and one employee.

Results: Of 102 participating businesses (95% Hispanic-owned), 96% were characterized as "high risk" or "very high risk" for disease transmission. All businesses reported implementing at least one practice to reduce disease transmission; however, almost half of businesses lacked …


Continuous Vital Sign Monitoring On Surgical Wards: The Cosmos Pilot, Shuyi Li, Amber Clemens, Christine Perez, John W Beard, Daniel I Sessler Dec 2024

Continuous Vital Sign Monitoring On Surgical Wards: The Cosmos Pilot, Shuyi Li, Amber Clemens, Christine Perez, John W Beard, Daniel I Sessler

Faculty, Staff and Student Publications

Study objectives: Alerts for vital sign abnormalities seek to identify meaningful patient instability while limiting alarm fatigue. Optimal vital sign alarm settings for postoperative patients remain unknown, as is whether alerts lead to effective clinical responses reducing vital sign disturbances. We conducted a 2-phase pilot study to identify thresholds and delays and test the hypothesis that alerts from continuous monitoring reduce the duration of vital sign abnormalities.

Design: Two-phase pilot.

Patients: 250 adults having major non-cardiac surgery.

Setting: Surgical wards.

Intervention: All patients had routine vital sign monitoring by nurses at 4-h intervals. We initially continuously recorded clinician-blinded saturation, heart …


Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Abbas Dehghan, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries Dec 2024

Bivariate Genome-Wide Association Study Of Circulating Fibrinogen And C-Reactive Protein Levels, Abbas Dehghan, Maria Sabater-Lleal, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.

Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.

Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) …


Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor Nov 2024

Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children's TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff …


Building Capacity In Dissemination And Implementation Research: The Presence And Impact Of Advice Networks, Allison J L'Hotta, Rebekah R Jacob, Stephanie Mazzucca-Ragan, Russell E Glasgow, Sharon E Straus, Wynne E Norton, Ross C Brownson Nov 2024

Building Capacity In Dissemination And Implementation Research: The Presence And Impact Of Advice Networks, Allison J L'Hotta, Rebekah R Jacob, Stephanie Mazzucca-Ragan, Russell E Glasgow, Sharon E Straus, Wynne E Norton, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: As dissemination and implementation (D&I) research increases, we must continue to expand training capacity and research networks. Documenting, understanding, and enhancing advice networks identifies key connectors and areas where networks are less established. In 2012 Norton et al. mapped D&I science advice and collaboration networks. The current study builds on this work and aims to map current D&I research advice networks.

METHODS: D&I researchers in the United States (US) and Canada were identified through a combination of publication metrics, and key persons identified networks and were invited to participate (n = 1,576). In this social network analysis study, participants …


A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min Nov 2024

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …


Human Single Cell Rna-Sequencing Reveals A Targetable Cd8+ Exhausted T Cell Population That Maintains Mouse Low-Grade Glioma Growth, Rasha Barakat, Jit Chatterjee, Rui Mu, Xuanhe Qi, Xingxing Gu, Igor Smirnov, Olivia Cobb, Karen Gao, Angelica Barnes, Jonathan Kipnis, David H Gutmann Nov 2024

Human Single Cell Rna-Sequencing Reveals A Targetable Cd8+ Exhausted T Cell Population That Maintains Mouse Low-Grade Glioma Growth, Rasha Barakat, Jit Chatterjee, Rui Mu, Xuanhe Qi, Xingxing Gu, Igor Smirnov, Olivia Cobb, Karen Gao, Angelica Barnes, Jonathan Kipnis, David H Gutmann

2020-Current year OA Pubs

In solid cancers, T cells typically function as cytotoxic effectors to limit tumor growth, prompting therapies that capitalize upon this antineoplastic property (immune checkpoint inhibition; ICI). Unfortunately, ICI treatments have been largely ineffective for high-grade brain tumors (gliomas; HGGs). Leveraging several single-cell RNA sequencing datasets, we report greater CD8


Creating A Sense Of Place When Implementing A New Emergency Department In Denmark: A Qualitative Study, Jeanette Wassar Kirk, Per Nilsen, Ove Andersen, Nina Thórný Stefánsdóttir, Mette Bendtz Lindstrøm, Byron J Powell, Tine Tjørnhøj-Thomsen Nov 2024

Creating A Sense Of Place When Implementing A New Emergency Department In Denmark: A Qualitative Study, Jeanette Wassar Kirk, Per Nilsen, Ove Andersen, Nina Thórný Stefánsdóttir, Mette Bendtz Lindstrøm, Byron J Powell, Tine Tjørnhøj-Thomsen

2020-Current year OA Pubs

BACKGROUND: Physical locations play an essential yet often overlooked role in healthcare implementation processes. Implementation Science frameworks such as the Theoretical Domains Framework, the Consolidated Framework for Implementation Research, and the Implementation in Context framework acknowledge the importance of the physical environment, but they often treat it as a passive backdrop for change. However, from a cultural geographic perspective, spaces and places are dynamic, influencing behavior, social structures, and the acceptance of new practices. This study aims to explore how managers and emloyees develop a sense of place in a new emergency department (ED) and how these spatial dynamics influence …


Myt1l Deficiency Impairs Excitatory Neuron Trajectory During Cortical Development, Allen Yen, Simona Sarafinovska, Xuhua Chen, Dominic D Skinner, Fatjon Leti, Marialynn Crosby, Jessica Hoisington-Lopez, Yizhe Wu, Jiayang Chen, Zipeng A Li, Kevin K Noguchi, Robi D Mitra, Joseph D Dougherty Nov 2024

Myt1l Deficiency Impairs Excitatory Neuron Trajectory During Cortical Development, Allen Yen, Simona Sarafinovska, Xuhua Chen, Dominic D Skinner, Fatjon Leti, Marialynn Crosby, Jessica Hoisington-Lopez, Yizhe Wu, Jiayang Chen, Zipeng A Li, Kevin K Noguchi, Robi D Mitra, Joseph D Dougherty

2020-Current year OA Pubs

Mutations reducing the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. MYT1L is used as a pro-neural factor in fibroblast-to-neuron transdifferentiation and is hypothesized to influence neuronal specification and maturation, but it is not clear which neuron types are most impacted by MYT1L loss. In this study, we profile 412,132 nuclei from the forebrains of wild-type and MYT1L-deficient mice at three developmental stages: E14 at the peak of neurogenesis, P1 when cortical neurons have been born, and P21 when neurons are maturing, to examine the role of MYT1L levels on neuronal development. MYT1L deficiency …


Cognition In Patients With Mild Autonomous Cortisol Secretion At Baseline And Post-Adrenalectomy, Jasmine Saini, Rohit Nathani, Sumitabh Singh, Andreas Ebbehoj, Karthik Thangamuthu, Malavika Suresh, Catherine D Zhang, Sophia Nevin, Vanessa Fell, Elizabeth J Atkinson, Sara J Achenbach, Nikki H Stricker, Irina Bancos Nov 2024

Cognition In Patients With Mild Autonomous Cortisol Secretion At Baseline And Post-Adrenalectomy, Jasmine Saini, Rohit Nathani, Sumitabh Singh, Andreas Ebbehoj, Karthik Thangamuthu, Malavika Suresh, Catherine D Zhang, Sophia Nevin, Vanessa Fell, Elizabeth J Atkinson, Sara J Achenbach, Nikki H Stricker, Irina Bancos

Faculty, Staff and Students Publications

Objectives: The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition.

Methods: We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021 to 9/2023) of adults with MACS and referent subjects. Cognition was assessed with National Institute of Health Toolbox Cognition Battery and reported as standardized T scores (adjusted for age, sex, race/ethnicity, and education) for fluid, crystallized, and total composite cognition. Participants were assessed with urine steroid profiling (liquid …