Public Health Commons^™

Prevention, Diagnosis, Evaluation, And Treatment Of Hepatitis C In Chronic Kidney Disease: Synopsis Of The Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline, Ahmed Arslan Yousuf Awan, Marina C Berenguer, Annette Bruchfeld, Fabrizio Fabrizi, David S Goldberg, Jidong Jia, Nassim Kamar, Rosmawati Mohamed, Mário Guimarães Pessôa, Stanislas Pol, Meghan E Sise, Ethan M Balk, Craig E Gordon, Gaelen Adam, Michael Cheung, Amy Earley, Paul Martin, Michel Jadoul

Faculty, Staff and Students Publications

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO.

Methods: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters …

Case Sampling Vs Universal Review For Evaluating Hospital Postoperative Mortality In Us Surgical Quality Improvement Programs, Vivi W Chen, Alexis P Chidi, Tracey Rosen, Yongquan Dong, Peter A Richardson, Jennifer Kramer, David A Axelrod, Laura A Petersen, Nader N Massarweh

Faculty, Staff and Students Publications

IMPORTANCE: Representative surgical case sampling, rather than universal review, is used by US Department of Veterans Affairs (VA) and private-sector national surgical quality improvement (QI) programs to assess program performance and to inform local QI and performance improvement efforts. However, it is unclear whether case sampling is robust for identifying hospitals with safety or quality concerns.

OBJECTIVE: To evaluate whether the sampling strategy used by several national surgical QI programs provides hospitals with data that are representative of their overall quality and safety, as measured by 30-day mortality.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study was a national, hospital-level …

Association Of The Covid-19 Pandemic With Women, Infants, And Children (Wic) Receipt Among Pregnant Individuals: United States, 2016-2022, Savannah Busch, Jennifer A Andersen, Don E Willis, Pearl Anna Mcelfish, Sharon Reece, Dominique Dubois, Clare C Brown

Faculty, Staff and Students Publications

Objectives. To evaluate the effect of COVID-19 on Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) receipt among pregnant individuals overall and by race/ethnicity.

Methods. We measured changes in WIC receipt among Medicaid-covered births (n = 10 484 697) from the US National Center for Health Statistics Natality Files (2016–2022). Our interrupted time series logistic model included a continuous monthly variable, a binary post-COVID variable, and a continuous slope shift variable. We additionally fit separate models for each race/ethnicity relative to White individuals, using interaction terms between the time series variables and race/ethnicity.

Results. We found decreases in …

Feasibility Of Pevonedistat Combined With Azacitidine, Fludarabine, Cytarabine In Pediatric Relapsed/Refractory Aml: Results From Cog Advl1712, Katherine Tarlock, Xiaowei Liu, Charles G Minard, Emasenyie A Isikwei, Joel M Reid, Terzah M Horton, Elizabeth Fox, Brenda J Weigel, Todd Cooper

Faculty, Staff and Students Publications

Background:

Outcomes for children with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are poor and new therapies are needed. Pevonedistat is an inhibitor of the NEDD-8 activating enzyme, a key regulator of the ubiquitin proteasome system that is responsible for protein turnover, with protein degradation regulating cell growth and survival.

Procedure:

We evaluated the feasibility, toxicity, and pharmacokinetics (PK) of pevonedistat (20 mg/m² days 1, 3, 5) in combination with azacitidine, fludarabine, cytarabine (aza-FLA) in children with R/R AML and MDS (NCT03813147). Twelve patients were enrolled, median age was 13 years (range 1-21). Median …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 …

Genetics Of Predicted Platelet Reactivity, Paul S De Vries

Faculty, Staff and Student Publications

No abstract provided.

Varlock: Sequencing-Independent, Rapid Detection Of Sars-Cov-2 Variants Of Concern For Point-Of-Care Testing, Qpcr Pipelines And National Wastewater Surveillance, Xinsheng Nan, Patrick Hardinge, Sven Hoehn, Shrinivas Nivrutti Dighe, John Ukeri, Darius F Pease, Joshua Griffin, Jessica I Warrington, Zack Saud, Emma Hottinger, Gordon Webster, Davey Jones, Peter Kille, Andrew Weightman, Richard Stanton, Oliver K Castell, James A H Murray, Tomasz P Jurkowski

Faculty, Staff and Student Publications

The COVID-19 pandemic demonstrated the need for rapid molecular diagnostics. Vaccination programs can provide protection and facilitate the opening of society, but newly emergent and existing viral variants capable of evading the immune system endanger their efficacy. Effective surveillance for Variants of Concern (VOC) is therefore important. Rapid and specific molecular diagnostics can provide speed and coverage advantages compared to genomic sequencing alone, benefitting the public health response and facilitating VOC containment. Here we expand the recently developed SARS-CoV-2 CRISPR-Cas detection technology (SHERLOCK) to provide rapid and sensitive discrimination of SARS-CoV-2 VOCs that can be used at point of care, …

Mechanisms Of Ferroptosis And Targeted Therapeutic Approaches In Lymphoma, Tiantian Yu, Zijun Y Xu-Monette, Li Yu, Yong Li, Ken H Young

Faculty, Staff and Students Publications

Lymphoma is the sixth most common type of cancer worldwide. Under the current treatment standards, patients with lymphoma often fail to respond to treatment or relapse early and require further therapy. Hence, novel therapeutic strategies need to be explored and our understanding of the molecular underpinnings of lymphomas should be expanded. Ferroptosis, a non-apoptotic regulated cell death, is characterized by increased reactive oxygen species and lipid peroxidation due to metabolic dysfunction. Excessive or lack of ferroptosis has been implicated in tumor development. Current preclinical evidences suggest that ferroptosis participates in tumorigenesis, progression, and drug resistance of lymphoma, identifying a potential …

Hyperleptinemia Contributes To Antipsychotic Drug-Associated Obesity And Metabolic Disorders, Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Joel K Elmquist, Olivia Osborn, Chen Liu, Philipp E Scherer

Faculty, Staff and Students Publications

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly …

Eicosanoid And Eicosanoid-Related Inflammatory Mediators And Exercise Intolerance In Heart Failure With Preserved Ejection Fraction, Emily S Lau, Athar Roshandelpoor, Shahrooz Zarbafian, Dongyu Wang, James S Guseh, Norrina Allen, Vinithra Varadarajan, Matthew Nayor, Ravi V Shah, Joao A C Lima, Sanjiv J Shah, Bing Yu, Mona Alotaibi, Susan Cheng, Mohit Jain, Gregory D Lewis, Jennifer E Ho

Faculty, Staff and Student Publications

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.

Evaluation Of The Us Covid-19 Scenario Modeling Hub For Informing Pandemic Response Under Uncertainty, Emily Howerton, Lucie Contamin, Luke C Mullany, Michelle Qin, Nicholas G Reich, Samantha Bents, Rebecca K Borchering, Sung-Mok Jung, Sara L Loo, Claire P Smith, John Levander, Jessica Kerr, J Espino, Willem G Van Panhuis, Harry Hochheiser, Marta Galanti, Teresa Yamana, Sen Pei, Jeffrey Shaman, Kaitlin Rainwater-Lovett, Matt Kinsey, Kate Tallaksen, Shelby Wilson, Lauren Shin, Joseph C Lemaitre, Joshua Kaminsky, Juan Dent Hulse, Elizabeth C Lee, Clifton D Mckee, Alison Hill, Dean Karlen, Matteo Chinazzi, Jessica T Davis, Kunpeng Mu, Xinyue Xiong, Ana Pastore Y Piontti, Alessandro Vespignani, Erik T Rosenstrom, Julie S Ivy, Maria E Mayorga, Julie L Swann, Guido España, Sean Cavany, Sean Moore, Alex Perkins, Thomas Hladish, Alexander Pillai, Kok Ben Toh, Ira Longini, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Anass Bouchnita, Kaiming Bi, Michael Lachmann, Spencer J Fox, Lauren Ancel Meyers, Ajitesh Srivastava, Przemyslaw Porebski, Srini Venkatramanan, Aniruddha Adiga, Bryan Lewis, Brian Klahn, Joseph Outten, Benjamin Hurt, Jiangzhuo Chen, Henning Mortveit, Amanda Wilson, Madhav Marathe, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Betsy L Cadwell, Jessica M Healy, Rachel B Slayton, Michael A Johansson, Matthew Biggerstaff, Shaun Truelove, Michael C Runge, Katriona Shea, Cécile Viboud, Justin Lessler

Faculty, Staff and Student Publications

Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival …

A Multicenter Retrospective Cohort Study To Characterize Patients Hospitalized With Multisystem Inflammatory Syndrome In Adults And Coronavirus Disease 2019 In The United States, 2020-2021, Michael Melgar, Joseph Y Abrams, Shana Godfred-Cato, Ami B Shah, Amit Garg, Andrew Strunk, Mangala Narasimhan, Jonathan Koptyev, Alexandra Norden, David Musheyev, Fahmida Rashid, Rachel Tannenbaum, Rosa M Estrada-Y-Martin, Bela Patel, Siddharth Karanth, Chad J Achenbach, Gavin T Hall, Sara M Hockney, Matthew Caputo, Lilian M Abbo, Laura Beauchamps, Stephen Morris, Renzo O Cifuentes, Annabelle De St Maurice, Douglas S Bell, Kavitha K Prabaker, Fernando J Sanz Vidorreta, Evan Bryant, David K Cohen, Rohith Mohan, Christopher P Libby, Spencer Soohoo, Tristel J Domingo, Angela P Campbell, Ermias D Belay

Faculty, Staff and Student Publications

Background: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management.

Methods: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, …

First-Line Selpercatinib Or Chemotherapy And Pembrolizumab In Ret Fusion-Positive Nsclc, Caicun Zhou, Benjamin Solomon, Herbert H Loong, Keunchil Park, Maurice Pérol, Edurne Arriola, Silvia Novello, Baohui Han, Jianying Zhou, Andrea Ardizzoni, M Perez Mak, Fernando C Santini, Yasir Y Elamin, Alexander Drilon, Jürgen Wolf, Nalin Payakachat, Minji K Uh, Deborah Rajakumar, Hongmei Han, Tarun Puri, Victoria Soldatenkova, A Bence Lin, Boris K Lin, Koichi Goto, Libretto-431 Trial Investigators

Faculty, Staff and Student Publications

Background: Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study.

Methods: In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were …

Circulating Metabolites May Illustrate Relationship Of Alcohol Consumption With Cardiovascular Disease, Yi Li, Mengyao Wang, Xue Liu, Jian Rong, Patricia Emogene Miller, Roby Joehanes, Tianxiao Huan, Xiuqing Guo, Jerome I Rotter, Jennifer A Smith, Bing Yu, Matthew Nayor, Daniel Levy, Chunyu Liu, Jiantao Ma

Faculty, Staff and Student Publications

BACKGROUND: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.

METHODS: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Reducing Prescribing Of Antibiotics For Acute Respiratory Infections Using A Frontline Nurse-Led Ehr-Integrated Clinical Decision Support Tool: Protocol For A Stepped Wedge Randomized Control Trial, Elizabeth R Stevens, Ruth Agbakoba, Devin M Mann, Rachel Hess, Safiya I Richardson, Thomas Mcginn, Paul D Smith, Wendy Halm, Marlon P Mundt, Katherine L Dauber-Decker, Simon A Jones, Dawn M Feldthouse, Eun Ji Kim, David A Feldstein

Faculty, Staff and Students Publications

Background: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model.

Methods: Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested …

Correlations Between Mental Health, Physical Activity, And Body Composition In American College Students After The Covid-19 Pandemic Lockdown, Luis Torres, Manuela C Caciula, Alin S Tomoiaga, Carmen Gugu-Gramatopol

Faculty, Staff and Student Publications

Restrictions associated with the COVID-19 pandemic had forced American college students to significantly reduce their daily energy expenditure and increase their sedentary behaviors, thus presumably increasing mental health symptoms, decreasing physical activity levels, and enhancing the promotion of unhealthy eating habits. This study aimed to explore the correlations between mental health symptoms, physical activity levels, and body composition in college students in the years following the pandemic, focusing on the lingering effects of lockdown measures. American college students completed pre-existing, well-validated surveys for both mental health (Hospital Anxiety and Depression Scale) and physical activity (International Physical Activity Questionnaire—Long Form). Body …

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Black-White Disparities In Colorectal Cancer Outcomes: A Simulation Study Of Screening Benefit, Carolyn M Rutter, Pedro Nascimento De Lima, Christopher E Maerzluft, Folasade P May, Caitlin C Murphy

Faculty, Staff and Student Publications

The US Black population has higher colorectal cancer (CRC) incidence rates and worse CRC survival than the US White population, as well as historically lower rates of CRC screening. The Surveillance, Epidemiology, and End Results incidence rate data in people diagnosed between the ages of 20 and 45 years, before routine CRC screening is recommended, were analyzed to estimate temporal changes in CRC risk in Black and White populations. There was a rapid rise in rectal and distal colon cancer incidence in the White population but not the Black population, and little change in proximal colon cancer incidence for both …

Ischemic Bowel Associated With Newly Diagnosed Patent Foramen Ovale, Hannah Hong, Deanna Glassman, Shannon Neville Westin

Faculty, Staff and Student Publications

No abstract provided.

See Me, Hear Me, Know Me: Perspectives On Diet And Physical Activity Influences Among Teens Living In Rural Texas Communities, Debbe Thompson, Julie Miranda, Chishinga Callender, Jayna M Dave, Godlove Appiah, Salma M A Musaad

Faculty, Staff and Students Publications

Teens in rural communities are at greater risk of obesity than teens in urban areas. Diet and physical activity influence obesity risk. Understanding their perspectives is an important step in intervention design. This qualitative investigation explored teen perspectives on how living in a rural community influenced their diet and physical activity choices. Forty parent-teen pairs were recruited. Data collection included surveys and telephone interviews. This paper reports teen perspectives identified in the first interview. Thematic analysis was used to code and analyze the data. Findings revealed that the primary factor driving teens' diet and physical activity behaviors was the teens …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Faculty, Staff and Student Publications

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Association Between Lack Of Access To A Neighborhood Park And High Blood Pressure In The Philadelphia Metropolitan Area, Stephanie Kjelstrom, Richard W. Hass, Russell K. Mcintire

College of Population Health Faculty Papers

INTRODUCTION: Studies have shown a lower risk of high blood pressure (HBP) among people who live near parks; however, little information exists on how feeling safe and comfortable visiting the park affects blood pressure. We identified associations between neighborhood park access, comfort visiting a park, and HBP to understand how these factors may contribute to disparities in HBP prevalence.

METHODS: The 2018 Southeastern Pennsylvania Household Health Survey of 3,600 residents in the Philadelphia metropolitan area asked if respondents had ever been told they had HBP and whether they had a neighborhood park or outdoor space that they were comfortable visiting …

Estimating Heritability Explained By Local Ancestry And Evaluating Stratification Bias In Admixture Mapping From Summary Statistics, Tsz Fung Chan, Xinyue Rui, David V Conti, Myriam Fornage, Mariaelisa Graff, Jeffrey Haessler, Christopher Haiman, Heather M Highland, Su Yon Jung, Eimear E Kenny, Charles Kooperberg, Loic Le Marchand, Kari E North, Ran Tao, Genevieve Wojcik, Christopher R Gignoux, Charleston W K Chiang, Nicholas Mancuso

Faculty, Staff and Student Publications

The heritability explained by local ancestry markers in an admixed population (h

Gut Microbiota Composition And Diversity Before, During, And Two Months After Rifamycin-Based Tuberculosis Preventive Therapy, Marie Nancy Séraphin, Julia Bellot, Emily Klann, Maria Ukhanova, Florence G Saulsberry, Charles A Peloquin, Volker Mai

Faculty, Staff and Student Publications

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after …

Screening For Lung Cancer: 2023 Guideline Update From The American Cancer Society, Andrew M. D. Wolf, Kevin C. Oeffinger, Tina Ya-Chen Shih, Louise C. Walter, Timothy R. Church, Elizabeth T. H. Fontham, Elena B. Elkin, Ruth D. Etzioni, Carmen E. Guerra, Rebecca B. Perkins, Karli K. Kondo, Tyler B. Kratzer, Deanna Manassaram-Baptiste, William L. Dahut, Robert A. Smith

School of Public Health Faculty Publications

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS …

Transposable Elements Are Co-Opted As Oncogenic Regulatory Elements By Lineage-Specific Transcription Factors In Prostate Cancer, Giacomo Grillo, Tina Keshavarzian, Simon Linder, Christopher Arlidge, Lisanne Mout, Ankita Nand, Mona Teng, Aditi Qamra, Stanley Zhou, Ken J Kron, Alex Murison, James R Hawley, Michael Fraser, Theodorus H Van Der Kwast, Ganesh V Raj, Housheng Hansen He, Wilbert Zwart, Mathieu Lupien

Faculty, Staff and Student Publications

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a …

Differences In The Circulating Proteome In Individuals With Versus Without Sickle Cell Trait, Yanwei Cai, Nora Franceschini, Aditya Surapaneni, Melanie E Garrett, Usman A Tahir, Li Hsu, Marilyn J Telen, Bing Yu, Hua Tang, Yun Li, Simin Liu, Robert E Gerszten, Josef Coresh, Joann E Manson, Genevieve L Wojcik, Charles Kooperberg, Paul L Auer, Matthew W Foster, Morgan E Grams, Allison E Ashley-Koch, Laura M Raffield, Alex P Reiner

Faculty, Staff and Student Publications

BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests that sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including kidney failure. The mechanisms underlying these associations remain poorly understood. We used proteomic profiling to gain insight into the pathobiology of sickle cell trait.

METHODS: We measured proteomics ( N =1285 proteins assayed by Olink Explore) using baseline plasma samples from 592 Black participants with sickle cell trait and 1:1 …

Feasibility And Implementation Determinants Of A Structured Goal Setting And Goal Management System, Eunyoung Kang, Julie Chen, Erin R Foster

Faculty, Staff and Student Publications

Importance: There is no evidence-based system to guide occupational therapists in implementing theory-based, client-engaged goal setting and goal management. A new system is needed to support high-quality goal setting and goal management.

Objective: To determine the acceptability, appropriateness, feasibility, credibility, and expectancy of a new structured theory-based, client-engaged goal setting and goal management system, called MyGoals, for occupational therapists. We explored MyGoals' implementation determinants, potential positive outcomes, and comparative advantages.

Design: This was a mixed-methods feasibility study.

Setting: Community.

Participants: Occupational therapists (N = 7).

Outcomes and measures: Acceptability, appropriateness, and feasibility were assessed using the Acceptability of Intervention Measure …