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Investigating The Role Of Abro1 In Dna Damage-Induced Immune Response, Ahmed Emam Aug 2021

Investigating The Role Of Abro1 In Dna Damage-Induced Immune Response, Ahmed Emam

Dissertations and Theses (Open Access)

Genomic instability can be induced by various forms of genotoxic stress and it is a hallmark of human cancer that is associated with metastasis, therapeutic resistance, and poor prognosis. During replication stress, the replication fork stalls and forms a reversed fork which may be degraded by several DNA nucleases. At the stalled fork, genome stability is maintained by fork end protection and subsequent restart of the replication. Abro1 has been shown to play an important role in protecting the integrity of the stalled replication forks by inhibiting DNA2 nuclease. Deficiency of Abro1 leads to stalled replication fork degradation and genomic …


Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta Aug 2021

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations and Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …


The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun Aug 2021

The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun

Dissertations and Theses (Open Access)

Background: Prior studies showed that BRCA-deficient high grade serous ovarian carcinoma (HGSOC) had increased tumor infiltrating lymphocytes (TILs) compared to BRCA-wildtype (WT). To better understand the underlying immune mechanism in these tumors, a preliminary transcriptome analysis was performed on a set of microdissected HGSOC tumor specimens with BRCA1-mutation, BRCA2-mutation, or WT. This demonstrated an upregulation of IFITM3, an essential gene in modulating immune function. Based on these findings, we hypothesized that BRCA-deficient HGSOC have increased DNA damage leading to upregulation of IFITM3 and subsequent increase in antigen presentation and T-cell activation.

Methods: Following IRB approval, preliminary transcriptome analysis was performed …


Characterizing The Role Of Uchl5 In Metastatic Melanoma, Seenya Vincent Aug 2021

Characterizing The Role Of Uchl5 In Metastatic Melanoma, Seenya Vincent

Dissertations and Theses (Open Access)

Metastatic melanoma is one of the most aggressive cancers. In recent years, the survival rate has improved with the introduction of immunotherapy. Our lab conducted an in vivo ORF screen to identify potential drivers of metastasis. UCHL5/UCH37 was identified as one of the top candidates. UCHL5 is a deubiquitinating enzyme and interacts with the 26S proteasome complex and the INO80 chromatin remodeling complex. While UCHL5 has been shown to be overexpressed in many cancers, it has not been well characterized in melanoma. We investigated the role of UCHL5 in metastatic melanoma in vitro through overexpressing and knocking down UCHL5 in …


Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei Aug 2021

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations and Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …


Investigation Of Trophon® 2 For High Level Disinfection Of Rigid Endorectal Mri Coils, Rebecca Ditusa Aug 2021

Investigation Of Trophon® 2 For High Level Disinfection Of Rigid Endorectal Mri Coils, Rebecca Ditusa

Dissertations and Theses (Open Access)

Clinical Magnetic Resonance Imaging is most widely known for anatomical images with good image resolution and superb soft-tissue contrast. However, changes tumor metabolism may precede changes in gross size of the tumor. Newer studies present the use of 13C in MR imaging to interrogate tumor metabolism. With this additional information, not only can the size and makeup of a tumor be obtained, but also information about its metabolic characteristics. An increase in glucose uptake and production of lactate in the presence of oxygen—aerobic glycolysis—identifies abnormal metabolism, and hence a potential increase in tumor aggressiveness. Traditional 1H MRI of the prostate …


Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras Aug 2021

Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

OBJECTIVE: to determine the incidence, types, and risk factors of musculoskeletal injuries in a military security forces population.

METHODS: Demographic and diagnostic data were retrieved on enlisted US Air Force security forces personnel who served on active duty between January 2009 and December 2018. Incidence rates and ratios were calculated using Poisson regression.

RESULTS: During 251,787 person-years of exposure, 62,489 personnel served on active duty. Of these, 40,771 (65.2%) were diagnosed with at least one musculoskeletal injury. The majority (60.1%) of the 164,078 unique musculoskeletal injuries were inflammation and pain secondary to overuse. After adjusting for other factors, women had …


Hypertrophic Cardiomyopathy Associated E22k Mutation In Myosin Regulatory Light Chain Decreases Calcium-Activated Tension And Stiffness And Reduces Myofilament Ca2+ Sensitivity, Jiajia Zhang, Li Wang, Katarzyna Kazmierczak, Hang Yun, Danuta Szczesna-Cordary, Masataka Kawai Aug 2021

Hypertrophic Cardiomyopathy Associated E22k Mutation In Myosin Regulatory Light Chain Decreases Calcium-Activated Tension And Stiffness And Reduces Myofilament Ca2+ Sensitivity, Jiajia Zhang, Li Wang, Katarzyna Kazmierczak, Hang Yun, Danuta Szczesna-Cordary, Masataka Kawai

Faculty, Staff and Student Publications

We investigated the mechanisms associated with E22K mutation in myosin regulatory light chain (RLC), found to cause hypertrophic cardiomyopathy (HCM) in humans and mice. Specifically, we characterized the mechanical profiles of papillary muscle fibers from transgenic mice expressing human ventricular RLC wild-type (Tg-WT) or E22K mutation (Tg-E22K). Because the two mouse models expressed different amounts of transgene, the B6SJL mouse line (NTg) was used as an additional control. Mechanical experiments were carried out on Ca

SUB-DISCIPLINE: Bioenergetics.

DATABASE: The data that support the findings of this study are available from the corresponding authors upon reasonable request.

ANIMAL PROTOCOL: BK20150353 (Soochow …


Genome-Wide Association Study Of Serum Metabolites In The African American Study Of Kidney Disease And Hypertension, Shengyuan Luo, Elena V Feofanova, Adrienne Tin, Sarah Tung, Eugene P Rhee, Josef Coresh, Dan E Arking, Aditya Surapaneni, Pascal Schlosser, Yong Li, Anna Köttgen, Bing Yu, Morgan E Grams Aug 2021

Genome-Wide Association Study Of Serum Metabolites In The African American Study Of Kidney Disease And Hypertension, Shengyuan Luo, Elena V Feofanova, Adrienne Tin, Sarah Tung, Eugene P Rhee, Josef Coresh, Dan E Arking, Aditya Surapaneni, Pascal Schlosser, Yong Li, Anna Köttgen, Bing Yu, Morgan E Grams

Faculty, Staff and Student Publications

The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. to date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1.73m


Library Upcoming Closure, Beatriz Varman Aug 2021

Library Upcoming Closure, Beatriz Varman

TMC Library Newsletter (2015-)

The TMC Library will be closed on Saturday, August 28th due to building maintenance, and Monday, September 6th in observance of Labor Day.


Anti-Neutrophil Cytoplasmic Antibodies: To Care Or Not To Care, Sara Shahid, Syed H Alam, Lillian Gaber, Salman Ahmed Aug 2021

Anti-Neutrophil Cytoplasmic Antibodies: To Care Or Not To Care, Sara Shahid, Syed H Alam, Lillian Gaber, Salman Ahmed

Faculty, Staff and Students Publications

Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis is a disease process with a wide range of presentations, from asymptomatic or minimally symptomatic disease with positive laboratory testing, to florid acute end-organ damage. Consensus has not been established as to the frequency and/or protocol by which ANCA testing should be repeated. We present the case of a 53-year-old woman who initially came to medical attention with persistent dyspnea and pulmonary infiltrates presumed to be due to acute exacerbation of chronic diastolic congestive heart failure. Extensive infectious disease testing was negative, but ANCA testing was positive. However, because antinuclear antibody (ANA) interference in …


Incorporating Machine Learning Algorithm In Modified Quality By Design Approach On Simulated Penicillin Fermentation Dataset, Shengting Xu Aug 2021

Incorporating Machine Learning Algorithm In Modified Quality By Design Approach On Simulated Penicillin Fermentation Dataset, Shengting Xu

Dissertations and Theses (Open Access)

For this thesis, we utilized random forest (RF) algorithm in combination with Quality by Design (QbD) in simulated commercial-scale penicillin production dataset. The RF algorithm was primarily used in the selection of critical process parameters (CPPs). In this analysis, the primary critical quality attributes (CQA) was set to be the final penicillin yield. After the CPPs were selected by the RF algorithm, we would propose design of experiment (DoE) by using fractional factorial design to establish mathematical relationships between CPPs and CQAs. Among the five RF models, we chose two models before proceeding to the DoE step. One using the …


The Design And Rationale Of A Multicenter Real-World Trial: The Southeastern Collaboration To Improve Blood Pressure Control In The Us Black Belt – Addressing The Triple Threat, Tina O Findley, Hope Northrup Aug 2021

The Design And Rationale Of A Multicenter Real-World Trial: The Southeastern Collaboration To Improve Blood Pressure Control In The Us Black Belt – Addressing The Triple Threat, Tina O Findley, Hope Northrup

Faculty, Staff and Student Publications

The incidence of congenital heart defect (CHD) has increased over the past fifty years, partly attributed to routine fetal anatomical examination by sonography during obstetric care and improvements in ultrasound technology and technique. Fetal findings on ultrasound in addition to maternal biomarkers are the backbone of first- and second-trimester screening for common genetic conditions, namely aneuploidy. Since the introduction of non-invasive prenatal testing (NIPT) using next-generation sequencing to sequence cell-free fetal DNA, the detection rate of common trisomies as well as sex chromosomal aneuploidies have markedly increased. As the use of NIPT continues to broaden, the best means of incorporating …


Double-Blind Randomized Proof-Of-Concept Trial Of Canakinumab In Patients With Covid-19 Associated Cardiac Injury And Heightened Inflammation, Paul C Cremer, Calvin C Sheng, Debasis Sahoo, Siddharth Dugar, Robier Aguillon Prada, Tom Kai Ming Wang, Ossama K Abou Hassan, Jamie Hernandez-Montfort, David A Wolinsky, Daniel A Culver, Prabalini Rajendram, Abhijit Duggal, Danielle M Brennan, Katherine E Wolski, A Michael Lincoff, Steven E Nissen, Venu Menon Aug 2021

Double-Blind Randomized Proof-Of-Concept Trial Of Canakinumab In Patients With Covid-19 Associated Cardiac Injury And Heightened Inflammation, Paul C Cremer, Calvin C Sheng, Debasis Sahoo, Siddharth Dugar, Robier Aguillon Prada, Tom Kai Ming Wang, Ossama K Abou Hassan, Jamie Hernandez-Montfort, David A Wolinsky, Daniel A Culver, Prabalini Rajendram, Abhijit Duggal, Danielle M Brennan, Katherine E Wolski, A Michael Lincoff, Steven E Nissen, Venu Menon

Faculty, Staff and Student Publications

AIMS: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1β, in patients with COVID-19, myocardial injury, and heightened inflammation.

METHODS AND RESULTS: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. …


Underreporting On The Mmpi-2-Rf Extends To Extra-Test Measures Of Suicide Risk, Lauren R Khazem, Katrina A Rufino, Megan L Rogers, Austin J Gallyer, Thomas E Joiner, Joye C Anestis Aug 2021

Underreporting On The Mmpi-2-Rf Extends To Extra-Test Measures Of Suicide Risk, Lauren R Khazem, Katrina A Rufino, Megan L Rogers, Austin J Gallyer, Thomas E Joiner, Joye C Anestis

Staff and Researcher Publications

Detection of under-reporting in suicide risk assessment remains a significant concern in clinical practice. The aim of this research is to examine whether under-reporting based on elevated MMPI-2-RF K-r and L-r scale scores may aid in identifying patients with suppressed scores on SUI and extra-test measures of suicide risk. We anticipated that, in voluntarily admitted psychiatric inpatients (N=1,011) and individuals receiving outpatient services in a university-affiliated psychology clinic (N=521), those indicated as under-reporting would produce lower mean scores across SUI and extra-test measures of suicide risk, and that the magnitudes of the associations between SUI and …


Thromboelastography-Based Profiling Of Coagulation Status In Patients Undergoing Bariatric Surgery: Analysis Of 422 Patients, John C Cowling, Xu Zhang, Kulvinder S Bajwa, Ekatarina G Elliott, Melissa M Felinski, Julie Holihan, Michelle Scerbo, Brad E Snyder, Michael D Trahan, Todd D Wilson, Sharon L Courtney, Connie L Klein, Angielyn R Rivera, Erik B Wilson, Shinil K Shah, Davide Cattano Aug 2021

Thromboelastography-Based Profiling Of Coagulation Status In Patients Undergoing Bariatric Surgery: Analysis Of 422 Patients, John C Cowling, Xu Zhang, Kulvinder S Bajwa, Ekatarina G Elliott, Melissa M Felinski, Julie Holihan, Michelle Scerbo, Brad E Snyder, Michael D Trahan, Todd D Wilson, Sharon L Courtney, Connie L Klein, Angielyn R Rivera, Erik B Wilson, Shinil K Shah, Davide Cattano

Faculty, Staff and Student Publications

Introduction/purpose: Some clinical indicators suggest hypercoagulability/hyperaggregability in patients with morbid obesity. Thromboelastography (TEG®) has been used to profile coagulation status in surgical patients. We aimed to assess coagulation profiles in patients with morbid obesity undergoing bariatric surgery by correlating demographic and patient characteristics to pre-operative TEG® values.

Materials and methods: Pre-operative TEG® values from 422 patients undergoing bariatric surgery were evaluated. TEG® results were analyzed by gender, use of medications known to alter the coagulation profile, and body mass index (BMI).

Results: Patients have a mean of 45.03 ± 11.8 years, female (76.3%), and with a mean BMI of 42 …


Enhancing The Teaching Environment: 3-Year Follow-Up Of A Resident-Led Residents-As-Teachers Program, Bani M Ratan, Grace J Johnson, Amanda C Williams, Jocelyn T Greely, Charlie C Kilpatrick Aug 2021

Enhancing The Teaching Environment: 3-Year Follow-Up Of A Resident-Led Residents-As-Teachers Program, Bani M Ratan, Grace J Johnson, Amanda C Williams, Jocelyn T Greely, Charlie C Kilpatrick

Faculty, Staff and Students Publications

BACKGROUND: Previous faculty-driven residents-as-teachers (RAT) models have had limited efficacy and sustainability.

OBJECTIVE: To evaluate the acceptability and effects of a

METHODS: In October 2016, obstetrics and gynecology (OB/GYN) residents at a large academic institution implemented a resident-led RAT program, consisting of a steering committee of peer-selected residents with 2 faculty mentors who planned education-focused resident didactics and journal clubs, organized resident involvement in clerkship activities, and recognized residents who excelled in teaching as Distinguished Educators (DEs). From July 2016 through June 2019, using the Kirkpatrick Model, we evaluated the program with annual resident surveys assessing self-perception of 13 teaching …


Factors Influencing Emergency Medicine Residency Choice: Diversity, Community, And Recruitment Red Flags, Paul L Weygandt, Laura Smylie, Edgardo Ordonez, Jaime Jordan, Arlene S Chung Aug 2021

Factors Influencing Emergency Medicine Residency Choice: Diversity, Community, And Recruitment Red Flags, Paul L Weygandt, Laura Smylie, Edgardo Ordonez, Jaime Jordan, Arlene S Chung

Faculty, Staff and Students Publications

BACKGROUND: Emergency medicine (EM) applicants consider many factors when selecting residency programs. Prior studies have demonstrated that applicants consider geography as well as modifiable/nonmodifiable program factors. Less attention, however, has been paid to underrepresented groups. Additionally, the prevalence and characteristics of "red flags," or factors that may lead an applicant to lower a program's rank or not rank it at all, remain unknown in EM. Our objective was to describe the factors that influence current EM-bound medical students' residency selection focusing on underrepresented applicants and red flags encountered during the recruitment process.

METHODS: We conducted a mixed-methods survey study of …


A Novel Incremental Simulation Of Facial Changes Following Orthognathic Surgery Using Fem With Realistic Lip Sliding Effect, Daeseung Kim, Tianshu Kuang, Yriu L Rodrigues, Jaime Gateno, Steve G F Shen, Xudong Wang, Kirhyn Stein, Hannah H Deng, Michael A K Liebschner, James J Xia Aug 2021

A Novel Incremental Simulation Of Facial Changes Following Orthognathic Surgery Using Fem With Realistic Lip Sliding Effect, Daeseung Kim, Tianshu Kuang, Yriu L Rodrigues, Jaime Gateno, Steve G F Shen, Xudong Wang, Kirhyn Stein, Hannah H Deng, Michael A K Liebschner, James J Xia

Faculty, Staff and Students Publications

Accurate prediction of facial soft-tissue changes following orthognathic surgery is crucial for surgical outcome improvement. We developed a novel incremental simulation approach using finite element method (FEM) with a realistic lip sliding effect to improve the prediction accuracy in the lip region. First, a lip-detailed mesh is generated based on accurately digitized lip surface points. Second, an improved facial soft-tissue change simulation method is developed by applying a lip sliding effect along with the mucosa sliding effect. Finally, the orthognathic surgery initiated soft-tissue change is simulated incrementally to facilitate a natural transition of the facial change and improve the effectiveness …


Utilizing Structured Worksheets To Strengthen Resident Teaching On The Ob/Gyn Clerkship, Matthew R Carroll, Charlie C Kilpatrick, Grace Johnson, Neelima Sukhavasi, Bani M Ratan Aug 2021

Utilizing Structured Worksheets To Strengthen Resident Teaching On The Ob/Gyn Clerkship, Matthew R Carroll, Charlie C Kilpatrick, Grace Johnson, Neelima Sukhavasi, Bani M Ratan

Faculty, Staff and Students Publications

OBJECTIVE: To determine if structured worksheets can aid resident teaching on the obstetrics and gynecology (OB/GYN) clerkship.

DESIGN: We developed structured worksheets to aid residents in teaching medical students. In this pilot study, we measured the impact of the material by conducting end of clerkship focus groups between October 2017 to June 2018 and administering surveys to medical students who had recently completed the clerkship. We performed analyses of the focus group transcriptions for positive and negative themes and analyzed questionnaire data utilizing unpaired t-test and chi-square test to determine whether resident use of structured worksheets influenced student perception of …


Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky Aug 2021

Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky

Faculty, Staff and Students Publications

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite …


Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown Aug 2021

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …


Cd148 Deficiency In Fibroblasts Promotes The Development Of Pulmonary Fibrosis, Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W Ryter, Kevin Xiong, Sarah G Chu, Xiaoli Liu, Bonna Ith, Lindsay J Celada, Freddy Romero, Matthew J Robertson, Anthony J Esposito, Sergio Poli, Souheil El-Chemaly, Mark A Perrella, Yuanyuan Shi, James Whiteford, Ivan O Rosas Aug 2021

Cd148 Deficiency In Fibroblasts Promotes The Development Of Pulmonary Fibrosis, Konstantin Tsoyi, Xiaoliang Liang, Giulia De Rossi, Stefan W Ryter, Kevin Xiong, Sarah G Chu, Xiaoli Liu, Bonna Ith, Lindsay J Celada, Freddy Romero, Matthew J Robertson, Anthony J Esposito, Sergio Poli, Souheil El-Chemaly, Mark A Perrella, Yuanyuan Shi, James Whiteford, Ivan O Rosas

Faculty, Staff and Students Publications

Rationale: CD148/PTRJ (receptor-like protein tyrosine phosphatase η) exerts antifibrotic effects in experimental pulmonary fibrosis via interactions with its ligand syndecan-2; however, the role of CD148 in human pulmonary fibrosis remains incompletely characterized.

Objectives: We investigated the role of CD148 in the profibrotic phenotype of fibroblasts in idiopathic pulmonary fibrosis (IPF).

Methods: Conditional CD148 fibroblast-specific knockout mice were generated and exposed to bleomycin and then assessed for pulmonary fibrosis. Lung fibroblasts (mouse lung and human IPF lung), and precision-cut lung slices from human patients with IPF were isolated and subjected to experimental treatments. A CD148-activating 18-aa mimetic peptide (SDC2-pep) derived from …


Deep Learning-Based Mixed-Dimensional Gaussian Mixture Model For Characterizing Variability In Cryo-Em, Muyuan Chen, Steven J Ludtke Aug 2021

Deep Learning-Based Mixed-Dimensional Gaussian Mixture Model For Characterizing Variability In Cryo-Em, Muyuan Chen, Steven J Ludtke

Faculty, Staff and Students Publications

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. Cryogenic electron microscopy (cryo-EM) provides direct visualization of individual macromolecules sampling different conformational and compositional states. While numerous methods are available for computational classification of discrete states, characterization of continuous conformational changes or large numbers of discrete state without human supervision remains challenging. Here we present e2gmm, a machine learning algorithm to determine a conformational landscape for proteins or complexes using a three-dimensional Gaussian mixture model mapped onto two-dimensional particle images in known orientations. Using a deep neural network architecture, e2gmm can automatically resolve the …


Rare Silent Ischemic Ventricular Septal Aneurysm And Rupture: A Multimodality Diagnostic Approach, Hong Loan Nguyen, Nicolas Palaskas, Nasser Lakkis, Rashed Tabbaa Aug 2021

Rare Silent Ischemic Ventricular Septal Aneurysm And Rupture: A Multimodality Diagnostic Approach, Hong Loan Nguyen, Nicolas Palaskas, Nasser Lakkis, Rashed Tabbaa

Faculty, Staff and Students Publications

A multimodality approach in addition to high level of clinical suspicion and thorough physical examination is important in the diagnosis and management of left ventricular aneurysm and rupture after a silent inferior infarction.


Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald Aug 2021

Thioredoxin Reductase Is A Major Regulator Of Metabolism In Leukemia Cells, Sheelarani Karunanithi, Ruifu Liu, Yongchun Hou, Giancarlo Gonzalez, Natasha Oldford, Anne Jessica Roe, Nethrie Idipilly, Kalpana Gupta, Chandra Sekhar Amara, Satwikreddy Putluri, Grace Kyueun Lee, Juan Valentin-Goyco, Lindsay Stetson, Stephen A Moreton, Vasanta Putluri, Shyam M Kavuri, Yogen Saunthararajah, Marcos De Lima, Gregory P Tochtrop, Nagireddy Putluri, David N Wald

Faculty, Staff and Students Publications

Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML …


Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li Aug 2021

Neurovascular Regulation In Diabetic Retinopathy And Emerging Therapies, Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for …


The Cgas–Sting Pathway In Diabetic Retinopathy And Age-Related Macular Degeneration, Shannon Erhardt, Mingjie Zheng, Xiaolei Zhao, Tram P Le, Tina O Findley, Jun Wang Jul 2021

The Cgas–Sting Pathway In Diabetic Retinopathy And Age-Related Macular Degeneration, Shannon Erhardt, Mingjie Zheng, Xiaolei Zhao, Tram P Le, Tina O Findley, Jun Wang

Faculty, Staff and Student Publications

The neural crest (NC) is a multipotent and temporarily migratory cell population stemming from the dorsal neural tube during vertebrate embryogenesis. Cardiac neural crest cells (NCCs), a specified subpopulation of the NC, are vital for normal cardiovascular development, as they significantly contribute to the pharyngeal arch arteries, the developing cardiac outflow tract (OFT), cardiac valves, and interventricular septum. Various signaling pathways are shown to orchestrate the proper migration, compaction, and differentiation of cardiac NCCs during cardiovascular development. Any loss or dysregulation of signaling pathways in cardiac NCCs can lead to abnormal cardiovascular development during embryogenesis, resulting in abnormalities categorized as …


Guest Editors' Introduction, Susan Pacheco, Ruth A. Etzel Jul 2021

Guest Editors' Introduction, Susan Pacheco, Ruth A. Etzel

Journal of Applied Research on Children: Informing Policy for Children at Risk

No abstract provided.


Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Karen L Weis, Tony T Yuan, Katherine C Walker, Thomas F Gibbons, Wenyaw Chan Jul 2021

Associations Between Physiological Biomarkers And Psychosocial Measures Of Pregnancy-Specific Anxiety And Depression With Support Intervention, Karen L Weis, Tony T Yuan, Katherine C Walker, Thomas F Gibbons, Wenyaw Chan

Faculty, Staff and Student Publications

Stress and anxiety significantly impact the hypothalamic-pituitary axis, and in pregnancy, the subsequent maternal-fetal response can lead to poor outcomes. The objective of this study was to assess the association between psychosocial measures of pregnancy-specific anxiety and physiologic inflammatory responses. Specifically, to determine the effectiveness of the Mentors Offering Maternal Support (M-O-M-S