Medicine and Health Sciences Commons^™

Relationship Between Obesity And Global Longitudinal Strain In The Pediatric Single Ventricle Fontan Population Across Ventricular Morphologies., Nitin Madan, Doaa Aly, Melanie Kathol, Amulya Buddhavarapu, Thomas Rieth, Ashley K. Sherman, Daniel Forsha

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Obesity is associated with diminished myocardial function as measured by strain echocardiography in children and young adults with normal cardiac anatomy. Data are lacking about the effect of obesity on myocardial strain in patients with a single ventricle. In this study, the relationship between body mass index (BMI) and single ventricle myocardial strain in the Fontan population was assessed.

METHODS AND RESULTS: Thirty-eight abnormal BMI Fontan cases (21 overweight and 17 obese) and 30 normal BMI Fontan controls matched based on single ventricular morphology, age, and sex were included in the study. Ventricular morphology was categorized as single right …

Development And Validation Of The American Heart Association's Prevent Equations, Sadiya S Khan, Kunihiro Matsushita, Yingying Sang, Shoshana H Ballew, Morgan E Grams, Aditya Surapaneni, Michael J Blaha, April P Carson, Alexander R Chang, Elizabeth Ciemins, Alan S Go, Orlando M Gutierrez, Shih-Jen Hwang, Simerjot K Jassal, Csaba P Kovesdy, Donald M Lloyd-Jones, Michael G Shlipak, Latha P Palaniappan, Laurence Sperling, Salim S Virani, Katherine Tuttle, Ian J Neeland, Sheryl L Chow, Janani Rangaswami, Michael J Pencina, Chiadi E Ndumele, Josef Coresh, Chronic Kidney Disease Prognosis Consortium And The American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group

Faculty, Staff and Students Publications

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD.

METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular …

Viral Dnaemia And Dna Virus Seropositivity And Mortality In Pediatric Sepsis, Stephanie S Cabler, Gregory A Storch, Andrew H Walton, John C Lin, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.

OBJECTIVE: To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG …

Immune Response To Sars-Cov-2 Variants After Immunization With Different Vaccines In Mexico, Erika Garay, Sean P J Whelan, Rebecca M Dubois, Sara M O'Rourke, Angel Eduardo Salgado-Escobar, José Esteban Muñoz-Medina, Carlos F Arias, Susana López

2020-Current year OA Pubs

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior …

Major Adverse Kidney Events In Pediatric Continuous Kidney Replacement Therapy, Dana Y Fuhrman, Tara M Neumayr, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death.

OBJECTIVE: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults.

DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury …

Hiv-Associated Gut Microbial Alterations Are Dependent On Host And Geographic Context, Muntsa Rocafort, Guoyan Zhao, Scott A Handley, Et Al.

2020-Current year OA Pubs

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men …

Opportunities For Pharmacogenetic Testing To Guide Dosing Of Medications In Youths With Medicaid., Sonya Tang Girdwood, Matthew Hall, James W. Antoon, Kathryn Kyler, Derek J. Williams, Samir S. Shah, Lucas E. Orth, Jennifer Goldman, James A. Feinstein, Laura B. Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement.

OBJECTIVES: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to …

The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

BACKGROUND: The most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target …

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Teaching And Safety-Net Hospital Penalization In The Hospital-Acquired Condition Reduction Program, Jose A Serpa, Gretchen Gemeinhardt, Cesar A Arias, Robert O Morgan, Heidi Russell, Hongyu Miao, Cecilia M Ganduglia Cazaban

Faculty, Staff and Student Publications

IMPORTANCE: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown.

OBJECTIVE: to determine hospital characteristics associated with HACRP penalization and penalization reversal.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP …

Fluvoxamine Inhibits Th1 And Th17 Polarization And Function By Repressing Glycolysis To Attenuate Autoimmune Progression In Type 1 Diabetes, Yuan Zou, Jing Zhang, Fei Sun, Qianqian Xu, Longmin Chen, Xi Luo, Ting Wang, Qing Zhou, Shu Zhang, Fei Xiong, Wen Kong, Ping Yang, Qilin Yu, Shiwei Liu, Cong-Yi Wang

Faculty, Staff and Student Publications

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.

METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune …

Serum Tumor Markers And Outcomes In Patients With Appendiceal Adenocarcinoma, Abdelrahman Yousef, Mahmoud Yousef, Mohammad A Zeineddine, Aditya More, Mohammad Fanaeian, Saikat Chowdhury, Mark Knafl, Paul Edelkamp, Ichiaki Ito, Yue Gu, Vinay Pattalachinti, Zahra Alavi Naini, Fadl A Zeineddine, Jennifer Peterson, Kristin Alfaro, Wai Chin Foo, Jeff Jin, Neal Bhutiani, Victoria Higbie, Christopher P Scally, Bryan Kee, Scott Kopetz, Drew Goldstein, Madeleine Strach, Andrew Williamson, Omer Aziz, Jorge Barriuso, Abhineet Uppal, Michael G White, Beth Helmink, Keith F Fournier, Kanwal P Raghav, Melissa W Taggart, Michael J Overman, John Paul Shen

Faculty, Staff and Student Publications

IMPORTANCE: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma.

OBJECTIVE: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD …

Nivolumab Monotherapy Or Combination With Ipilimumab With Or Without Cobimetinib In Previously Treated Patients With Pancreatic Adenocarcinoma (Checkmate 032), Margaret Callahan, Asim Amin, Frederic J Kaye, Michael A Morse, Matthew H Taylor, Katriina J Peltola, Padmanee Sharma, Eileen M O'Reilly, Stephanie Meadows Shropshire, Shaun O'Brien, Marina Tschaika, Dung T Le

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer.

METHODS: In the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one …

Evaluation Of A Tiered Opioid Prescription Algorithm In An Eras Pathway: Exploring Opportunities For Further Refinement, M Sol Basabe, Tina S Suki, Mark F Munsell, Maria D Iniesta, Juan E Garcia Lopez, Robert Tyler Hillman, Katherine Cain, Sarah Huepenbecker, Gabriel Mena, Jolyn S Taylor, Pedro T Ramirez, Larissa A Meyer

Faculty, Staff and Student Publications

Background: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription.

Objective: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education.

Methods: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription …

Health Economic Consequences Associated With Covid-19-Related Delay In Melanoma Diagnosis In Europe, Lara V Maul, Dagmar Jamiolkowski, Rebecca A Lapides, Alina M Mueller, Axel Hauschild, Claus Garbe, Paul Lorigan, Jeffrey E Gershenwald, Paolo Antonio Ascierto, Georgina V Long, Michael Wang-Evers, Richard A Scolyer, Babak Saravi, Matthias Augustin, Alexander A Navarini, Stefan Legge, István B Németh, Ágnes J Jánosi, Simone Mocellin, Anita Feller, Dieter Manstein, Alexander Zink, Julia-Tatjana Maul, Alessandra Buja, Kaustubh Adhikari, Elisabeth Roider

Faculty, Staff and Student Publications

IMPORTANCE: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet.

OBJECTIVE: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous …

Aneuploid Embryonic Stem Cells Drive Teratoma Metastasis, Rong Xiao, Deshu Xu, Meili Zhang, Zhanghua Chen, Li Cheng, Songjie Du, Mingfei Lu, Tonghai Zhou, Ruoyan Li, Fan Bai, Yue Huang

Faculty, Staff and Student Publications

Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities …

Neonatal Intensive Care Unit Resource Use For Infants At 22 Weeks' Gestation In The Us, 2008-2021, Matthew A Rysavy, Monica M Bennett, Kaashif A Ahmad, Ravi M Patel, Zubin S Shah, Dan L Ellsbury, Reese H Clark, Veeral N Tolia

Faculty, Staff and Student Publications

IMPORTANCE: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

OBJECTIVE: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants.

DESIGN, SETTING, AND PARTICIPANTS: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. …

Hospital-Level Nicu Capacity, Utilization, And 30-Day Outcomes In Texas, David C Goodman, Patrick Stuchlik, Cecilia Ganduglia-Cazaban, Jon E Tyson, Joanna Leyenaar, Elenir B C Avritscher, Mathew Rysavy, Kanekal S Gautham, David Lynch, Therese A Stukel

Faculty, Staff and Student Publications

IMPORTANCE: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood.

OBJECTIVE: To assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. …

Impact Of Individual Level Uncertainty Of Lung Cancer Polygenic Risk Score (Prs) On Risk Stratification, Xinan Wang, Ziwei Zhang, Yi Ding, Tony Chen, Lorelei Mucci, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angie Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Rayjean J Hung, Christopher I Amos, Xihong Lin, David C Christiani

Faculty, Staff and Student Publications

BACKGROUND: Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored.

METHODS: Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the …

Real-World Trends, Rural-Urban Differences, And Socioeconomic Disparities In Utilization Of Narrow Versus Broad Next-Generation Sequencing Panels, Yiqing Zhao, Anastasios Dimou, Zachary C Fogarty, Jun Jiang, Hongfang Liu, William B Wong, Chen Wang

Faculty, Staff and Student Publications

UNLABELLED: Advances in genetic technology have led to the increasing use of genomic panels in precision oncology practice, with panels ranging from a couple to hundreds of genes. However, the clinical utilization and utility of oncology genomic panels, especially among vulnerable populations, is unclear. We examined the association of panel size with socioeconomic status and clinical trial matching. We retrospectively identified 9,886 eligible adult subjects in the Mayo Clinic Health System who underwent genomic testing between January 1, 2016 and June 30, 2020. Patient data were retrieved from structured and unstructured data sources of institutional collections, including cancer registries, clinical …

Efficacy Of Novel Agents Against Cellular Models Of Familial Platelet Disorder With Myeloid Malignancy (Fpd-Mm), Christopher P Mill, Warren C Fiskus, Courtney D Dinardo, Patrick Reville, John A Davis, Christine E Birdwell, Kaberi Das, Hanxi Hou, Koichi Takahashi, Lauren Flores, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Joseph D Khoury, Kapil N Bhalla

Faculty, Staff and Student Publications

Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and …

Identification Of New Egfr Inhibitors By Structure-Based Virtual Screening And Biological Evaluation, Shuyi Wang, Xiaotian Xu, Chuxin Pan, Qian Guo, Qinlan Li, Shanhe Wan, Zhonghuang Li, Jiajie Zhang, Xiaoyun Wu

Faculty, Staff and Student Publications

Epidermal growth factor receptor (EGFR) inhibitors have been used in clinical for the treatment of non-small-cell lung cancer for years. However, the emergence of drug resistance continues to be a major problem. To identify potential inhibitors, molecular docking-based virtual screening was conducted on ChemDiv and Enamine commercial databases using the Glide program. After multi-step VS and visual inspection, a total of 23 compounds with novel and varied structures were selected, and the predicted ADMET properties were within the satisfactory range. Further molecular dynamics simulations revealed that the reprehensive compound ZINC49691377 formed a stable complex with the allosteric pocket of EGFR …

Unraveling The Complex Web Of Fibromyalgia: A Narrative Review., Sarah Al Sharie, Scott J Varga, Lou'i Al-Husinat, Piercarlo Sarzi-Puttini, Mohammad Araydah, Batool Riyad Bal'awi, Giustino Varrassi

Women’s Health Articles

Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diagnostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence transcending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. This study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Insights Of Clinical Significance From 109 695 Solid Tumor Tissue-Based Comprehensive Genomic Profiles, Andreas M Heilmann, Jonathan W Riess, Margaret Mclaughlin-Drubin, Richard S P Huang, Meghann Hjulstrom, James Creeden, Brian M Alexander, Rachel L Erlich

Faculty, Staff and Student Publications

BACKGROUND: FoundationOneCDx is approved in the US and Japan as a companion diagnostic test to identify patients with cancer who may benefit from treatment with 30 drug therapies in the US and 23 in Japan. Tumor profiling with FoundationOneCDx also detects genomic findings with evidence of clinical significance that may inform clinical care decisions beyond companion diagnostic claims. This observational study reports the breadth and impact of clinical decision insights from FoundationOneCDx solid tumor profiles.

MATERIALS AND METHODS: Consecutive test result reports for patients with solid tumor diagnoses (n = 109 695) were retrospectively analyzed for clinically significant predictive, prognostic, …

Patient Satisfaction With A Coach-Guided, Technology-Based Mental Health Treatment: Qualitative Interview Study And Theme Analysis, Ashley Helm Smith, Hilary Touchett, Patricia Chen, Terri Fletcher, Jennifer Arney, Julianna Hogan, Miryam Wassef, Marylene Cloitre, Jan A Lindsay

Faculty, Staff and Students Publications

Background: Technology-based mental health interventions address barriers rural veterans face in accessing care, including provider scarcity and distance from the hospital or clinic. webSTAIR is a 10-module, web-based treatment based on Skills Training in Affective and Interpersonal Regulation, designed to treat posttraumatic stress disorder and depression in individuals exposed to trauma. Previous work has demonstrated that webSTAIR is acceptable to participants and effective at reducing symptoms of posttraumatic stress disorder and depression when delivered synchronously or asynchronously (over 5 or 10 sessions).

Objective: This study explored factors that lead to greater patient satisfaction with webSTAIR, a web-based, coach-guided intervention.

Methods: …

Action Planning For Building Public Health Program Sustainability: Results From A Group-Randomized Trial, Sarah Moreland-Russell, Todd Combs, Jessica Gannon, Eliot Jost, Louise Farah Saliba, Kimberly Prewitt, Douglas Luke, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Public health programs are charged with implementing evidence-based interventions to support public health improvement; however, to achieve long-term population-based benefits, these interventions must be sustained. Empirical evidence suggests that program sustainability can be improved through training and technical assistance, but few resources are available to support public health programs in building capacity for sustainability.

METHODS: This study sought to build capacity for sustainability among state tobacco control programs through a multiyear, group-randomized trial that developed, tested, and evaluated a novel Program Sustainability Action Planning Model and Training Curricula. Using Kolb's experiential learning theory, we developed this action-oriented training model …

Rapid And Accurate Remethylation Of Dna In Dnmt3a- Deficient Hematopoietic Cells With Restoration Of Dnmt3a Activity, Yang Li, Haley J Abel, Michelle Cai, Taylor A Lavalle, Tiankai Yin, Nichole M Helton, Amanda M Smith, Christopher A Miller, Timothy J Ley

2020-Current year OA Pubs

Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of

A Comparative Biochemical And Pathological Evaluation Of Brain Samples From Knock-In Murine Models Of Gaucher Disease, Makaila L Furderer, Bahafta Berhe, Tiffany C Chen, Stephen Wincovitch, Xuntian Jiang, Nahid Tayebi, Ellen Sidransky, Tae-Un Han

2020-Current year OA Pubs

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in

Circulating Tumor Cells Prediction In Hormone Receptor Positive Her2-Negative Advanced Breast Cancer: A Retrospective Analysis Of The Monarch 2 Trial, Lorenzo Gerratana, Masha Kocherginsky, Andrew A Davis, Paolo D'Amico, Carolina Reduzzi, Fabio Puglisi, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials.

PATIENTS AND METHODS: Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage …