Digital Commons Network^™

Acute Myeloid Leukemia: Therapy Resistance And A Potential Role For Tetraspanin Membrane Scaffolds, Muskan Floren, Jennifer M. Gillette

Pathology Research and Scholarship

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family …

Standardizing Definitions Of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, And Donor Chimerism In Allogeneic Hematopoietic Cell Transplantation: A Report On Behalf Of The American Society For Transplantation And Cellular Therapy, Mohamed A Kharfan-Dabaja, Iskra Pusic, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and …

Effective Recruitment Strategies For A Sickle Cell Patient Registry Across Sites From The Sickle Cell Disease Implementation Consortium (Scdic), Rita V Masese, Taniya Varughese, Et Al.

2020-Current year OA Pubs

Sickle cell disease (SCD) is a genetic disorder predominantly affecting people of African descent and is associated with significant morbidity and mortality. To improve SCD outcomes, the National Heart Lung and Blood Institute funded eight centers to participate in the SCD Implementation Consortium. Sites were required to each recruit 300 individuals with SCD, over 20 months. We aim to describe recruitment strategies and challenges encountered. Participants aged 15-45 years with confirmed diagnosis of SCD were eligible. Descriptive statistics were used to analyze the effectiveness of each recruitment strategy. A total of 2432 participants were recruited. Majority (95.3%) were African American. …

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 …

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 …

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

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 …

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

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

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 …

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 …

Long-Term Evaluation Of A Course On Evidence-Based Public Health In The U.S. And Europe, Rebekah R Jacob, Carol A Brownson, Anjali D Deshpande, Amy A Eyler, Kathleen N Gillespie, Jennie Hefelfinger, Paul C Erwin, Marti Macchi, Ross C Brownson

2020-Current year OA Pubs

The evidence-based public health course equips public health professionals with skills and tools for applying evidence-based frameworks and processes in public health practice. To date, training has included participants from all the 50 U.S. states, 2 U.S. territories, and multiple other countries besides the U.S. This study pooled follow-up efforts (5 surveys, with 723 course participants, 2005-2019) to explore the benefits, application, and barriers to applying the evidence-based public health course content. All analyses were completed in 2020. The most common benefits (reported by >80% of all participants) were identifying ways to apply knowledge in their work, acquiring new knowledge, …

Race And Ethnicity Representation In Clinical Trials: Findings From A Literature Review Of Phase I Oncology Trials, D Ross Camidge, Haeseong Park, Karen E Smoyer, Ira Jacobs, Lauren J Lee, Zemfira Askerova, Justin Mcginnis, Yousef Zakharia

2020-Current year OA Pubs

No abstract provided.

Il-7 Expands Lymphocyte Populations And Enhances Immune Responses To Sipuleucel-T In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc), Russell K Pachynski, Chihiro Morishima, Et Al

2020-Current year OA Pubs

BACKGROUND: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).

METHODS: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using …

Phase Ii Study Of Durvalumab Plus Tremelimumab As Therapy For Patients With Previously Treated Anti-Pd-1/Pd-L1 Resistant Stage Iv Squamous Cell Lung Cancer (Lung-Map Substudy S1400f, Nct03373760), Natasha B Leighl, Jeffrey D Bradley, Et Al

2020-Current year OA Pubs

INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)).

METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate …

Efficacy Of Neratinib Plus Capecitabine In The Subgroup Of Patients With Central Nervous System Involvement From The Nala Trial, Sara A Hurvitz, Ron Bose, Et Al

2020-Current year OA Pubs

BACKGROUND: Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C).

MATERIALS AND METHODS: NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m

RESULTS: Of 621 patients enrolled, 101 (16.3%) …

Association Of Low Center Performance Evaluations And Pediatric Heart Transplant Center Behavior In The United States, Shahnawaz Amdani, Gerard Boyle, Joseph Rossano, Janet Scheel, Marc Richmond, Susana Arrigain, Jesse D Schold

2020-Current year OA Pubs

BACKGROUND: To date, no study has evaluated the effects of low center performance evaluations (CPE) on pediatric heart transplant center behavior. We sought to assess the impact of low CPE flags on pediatric heart transplant center listing and transplant volumes and center recipient and donor characteristics.

METHODS: We included centers performing at least 10 pediatric (age <18 years) transplants during the Scientific Registry of Transplant Recipients reporting period January 2009-June 2011 and evaluated consecutive biannual program specific reports until the last reporting period January 2016-June 2018. We evaluated changes in center behavior at following time points: a year before flagging, a year and two years after the flag; and at last reporting period.

RESULTS: During our study period, 24 pediatric centers were non-flagged and 6 were flagged. Compared to non-flagged centers, there was a decline in candidate listings in flagged centers at the last reporting period (mean increase of 5.5 ± 12.4 listings vs"?> mean decrease of …

Extracorporeal Photopheresis To Attenuate Decline In Lung Function Due To Refractory Obstructive Allograft Dysfunction, Epi Study Group, Chadi A Hage, Suresh Vedantham, Mary Clare Derfler, Paul Commean, Ed Spitznagel, Jeff Atkinson, George Despotis, Et Al.

2020-Current year OA Pubs

BACKGROUND: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV

STUDY DESIGN AND METHODS: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV

RESULTS: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion …

De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer

2020-Current year OA Pubs

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in …

Tumor-On-Chip Modeling Of Organ-Specific Cancer And Metastasis, Nuala Del Piccolo, Venktesh S Shirure, Ye Bi, S Peter Goedegebuure, Sepideh Gholami, Christopher C W Hughes, Ryan C Fields, Steven C George

2020-Current year OA Pubs

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology - a requirement for the development of more effective therapies for these patients - remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. …

Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

2020-Current year OA Pubs

IMPORTANCE: In the treatment of type 2 diabetes, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas-the second most widely used antihyperglycemic class after metformin-is lacking.

OBJECTIVE: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study used data from the US Department of Veterans Affairs compared the use of SGLT2 inhibitors vs sulfonylureas in individuals receiving metformin for treatment of type 2 diabetes. A total of 23 870 individuals with new use of …

Changes In The Gut Microbiome Influence The Hypoglycemic Effect Of Metformin Through The Altered Metabolism Of Branched-Chain And Nonessential Amino Acids, Yujin Lee, Andrew Hyoungjin Kim, Eunwoo Kim, Seunghwan Lee, Kyung-Sang Yu, In-Jin Jang, Jae-Yong Chung, Joo-Youn Cho

2020-Current year OA Pubs

AIMS: Although metformin has been reported to affect the gut microbiome, the mechanism has not been fully determined. We explained the potential underlying mechanisms of metformin through a multiomics approach.

METHODS: An open-label and single-arm clinical trial involving 20 healthy Korean was conducted. Serum glucose and insulin concentrations were measured, and stool samples were collected to analyze the microbiome. Untargeted metabolomic profiling of plasma, urine, and stool samples was performed by GC-TOF-MS. Network analysis was applied to infer the mechanism of the hypoglycemic effect of metformin.

RESULTS: The relative abundances of Escherichia, Romboutsia, Intestinibacter, and Clostridium were changed by metformin …

Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group

Open Access Publications

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.

METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study …

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

Effects Of A Dvd-Delivered Randomized Controlled Physical Activity Intervention On Functional Health In Cancer Survivors, Elizabeth A Salerno, Neha P Gothe, Jason Fanning, Lindsay L Peterson, Graham A Colditz, Edward Mcauley

2020-Current year OA Pubs

BACKGROUND: Supervised physical activity interventions improve functional health during cancer survivorship, but remain costly and inaccessible for many. We previously reported on the benefits of a DVD-delivered physical activity program (FlexToBa™) in older adults. This is a secondary analysis of the intervention effects among cancer survivors in the original sample.

METHODS: Low active, older adults who self-reported a history of cancer (N = 46; M time since diagnosis = 10.7 ± 9.4 years) participated in a 6-month, home-based physical activity intervention. Participants were randomized to either the DVD-delivered physical activity program focused on flexibility, toning, and balance (FlexToBa™; n = …

Impact Of Amerind Ancestry And Fads Genetic Variation On Omega-3 Deficiency And Cardiometabolic Traits In Hispanic Populations, Chaojie Yang, Brian Hallmark, Jin Choul Chai, Timothy D O'Connor, Lindsay M Reynolds, Alexis C Wood, Michael Seeds, Yii-Der Ida Chen, Lyn M Steffen, Michael Y Tsai, Robert C Kaplan, Martha L Daviglus, Lawrence J Mandarino, Amanda M Fretts, Rozenn N Lemaitre, Dawn K Coletta, Sarah A Blomquist, Laurel M Johnstone, Chandra Tontsch, Qibin Qi, Ingo Ruczinski, Stephen S Rich, Rasika A Mathias, Floyd H Chilton, Ani Manichaikul

Children’s Nutrition Research Center Staff Publications

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much …

Altered Neuronal Physiology, Development, And Function Associated With A Common Chromosome 15 Duplication Involving Chrna7, Kesavan Meganathan, Ramachandran Prakasam, Dustin Baldridge, Paul Gontarz, Bo Zhang, Fumihiko Urano, Azad Bonni, Susan E Maloney, Tychele N Turner, James E Huettner, John N Constantino, Kristen L Kroll

2020-Current year OA Pubs

BACKGROUND: Copy number variants (CNVs) linked to genes involved in nervous system development or function are often associated with neuropsychiatric disease. While CNVs involving deletions generally cause severe and highly penetrant patient phenotypes, CNVs leading to duplications tend instead to exhibit widely variable and less penetrant phenotypic expressivity among affected individuals. CNVs located on chromosome 15q13.3 affecting the alpha-7 nicotinic acetylcholine receptor subunit (CHRNA7) gene contribute to multiple neuropsychiatric disorders with highly variable penetrance. However, the basis of such differential penetrance remains uncharacterized. Here, we generated induced pluripotent stem cell (iPSC) models from first-degree relatives with a 15q13.3 duplication and …

Predictors Of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion., Trevor Simard, Richard G Jung, Kyle Lehenbauer, Kerstin Piayda, Radoslaw Pracoń, Gregory G Jackson, Eduardo Flores-Umanzor, Laurent Faroux, Kasper Korsholm, Julian K R Chun, Shaojie Chen, Moniek Maarse, Kristi Montrella, Zakeih Chaker, Jocelyn N Spoon, Luigi E Pastormerlo, Felix Meincke, Abhishek C Sawant, Carmen M Moldovan, Mohammed Qintar, Mehmet K Aktas, Luca Branca, Andrea Radinovic, Pradhum Ram, Rayan S El-Zein, Thomas Flautt, Wern Yew Ding, Bassel Sayegh, Tomás Benito-González, Oh-Hyun Lee, Solomon O Badejoko, Christina Paitazoglou, Nabeela Karim, Ahmed M Zaghloul, Himanshu Agrawal, Rachel M Kaplan, Oluseun Alli, Aamir Ahmed, Hussam S Suradi, Bradley P Knight, Venkata M Alla, Sidakpal S Panaich, Tom Wong, Martin W Bergmann, Rashaad Chothia, Jung-Sun Kim, Armando Pérez De Prado, Raveen Bazaz, Dhiraj Gupta, Miguel Valderrabano, Carlos E Sanchez, Mikhael F El Chami, Patrizio Mazzone, Marianna Adamo, Fred Ling, Dee Dee Wang, William O'Neill, Wojtek Wojakowski, Ashish Pershad, Sergio Berti, Daniel Spoon, Akram Kawsara, George Jabbour, Lucas V A Boersma, Boris Schmidt, Jens Erik Nielsen-Kudsk, Josep Rodés-Cabau, Xavier Freixa, Christopher R Ellis, Laurent Fauchier, Marcin Demkow, Horst Sievert, Michael L Main, Benjamin Hibbert, David R Holmes, Mohamad Alkhouli

Heart and Vascular Articles

BACKGROUND: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited.

OBJECTIVES: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT.

METHODS: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT.

RESULTS: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the …

Integrated Single-Cell Atlas Of Endothelial Cells Of The Human Lung, Jonas C Schupp, Taylor S Adams, Carlos Cosme, Micha Sam Brickman Raredon, Yifan Yuan, Norihito Omote, Sergio Poli, Maurizio Chioccioli, Kadi-Ann Rose, Edward P Manning, Maor Sauler, Giuseppe Deiuliis, Farida Ahangari, Nir Neumark, Arun C Habermann, Austin J Gutierrez, Linh T Bui, Robert Lafyatis, Richard W Pierce, Kerstin B Meyer, Martijn C Nawijn, Sarah A Teichmann, Nicholas E Banovich, Jonathan A Kropski, Laura E Niklason, Dana Pe'er, Xiting Yan, Robert J Homer, Ivan O Rosas, Naftali Kaminski

Faculty, Staff and Student Publications

BACKGROUND: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium.

METHODS: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species …

Potential Benefits Of Bovine Colostrum In Pediatric Nutrition And Health, Per Torp Sangild, Caitlin Vonderohe, Valeria Melendez Hebib, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing …