Medicine and Health Sciences Commons^™

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmmlafter Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Self-Administered Intranasal Etripamil Using A Symptom-Prompted, Repeat-Dose Regimen For Atrioventricular-Nodal-Dependent Supraventricular Tachycardia (Rapid): A Multicentre, Randomised Trial, Bruce S Stambler, A John Camm, Marco Alings, Paul Dorian, Hein Heidbuchel, Jaco Houtgraaf, Peter R. Kowey, Jose L Merino, Blandine Mondésert, Jonathan P Piccini, Sean D Pokorney, Philip T Sager, Atul Verma, J Marcus Wharton, David B Bharucha, Francis Plat, Silvia Shardonofsky, Michael Chen, James E Ip

Department of Medicine Faculty Papers

BACKGROUND: Etripamil is a fast-acting, intranasally administered calcium-channel blocker in development for on-demand therapy outside a health-care setting for paroxysmal supraventricular tachycardia. We aimed to evaluate the efficacy and safety of etripamil 70 mg nasal spray using a symptom-prompted, repeat-dose regimen for acute conversion of atrioventricular-nodal-dependent paroxysmal supraventricular tachycardia to sinus rhythm within 30 min.

METHODS: RAPID was a multicentre, randomised, placebo-controlled, event-driven trial, conducted at 160 sites in North America and Europe as part 2 of the NODE-301 study. Eligible patients were aged at least 18 years and had a history of paroxysmal supraventricular tachycardia with sustained, symptomatic episodes …

Overactive Bladder Syndrome Symptoms In Youth With Abdominal Pain-Associated Disorders Of Gut-Brain Interaction., Hunter J. Friesen, Pierce Thompson, Jennifer Verrill Schurman, Jennifer Colombo, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

The purpose of the current study was to assess the frequency of overactive bladder syndrome (OBS) symptoms and their relationship to gastrointestinal symptoms in youth with abdominal pain-associated disorders of gut-brain interaction (AP-DGBI). This is a retrospective study of 226 youth diagnosed with an AP-DGBI. As part of standard care, all patients completed a symptom questionnaire regarding gastrointestinal and non-gastrointestinal symptoms including increased urinary frequency, nighttime urination, and urinary urgency. Overall, 54% of patients reported at least one OBS symptom. Increased frequency of urination was reported by 19%, urinary urgency by 34%, and nighttime urination by 36%. Increased frequency of …

A Phase 1/2 Study Of Azacitidine, Venetoclax And Pevonedistat In Newly Diagnosed Secondary Aml And In Mds Or Cmml After Failure Of Hypomethylating Agents, Nicholas J Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax.

METHODS: This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m

FINDINGS: Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61-86 years), and …

Measuring The Effect Of Newborn Screening On Survival After Haematopoietic Cell Transplantation For Severe Combined Immunodeficiency: A 36-Year Longitudinal Study From The Primary Immune Deficiency Treatment Consortium, Monica S Thakar, Brent R Logan, Jennifer M Puck, Elizabeth A Dunn, Rebecca H Buckley, Morton J Cowan, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Sung-Yun Pai, Jennifer Heimall, Sharat Chandra, Christen L Ebens, Deepak Chellapandian, Olatundun Williams, Lauri M Burroughs, Blachy Davila Saldana, Ahmad Rayes, Lisa M Madden, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Geoffrey D E Cuvelier, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Frederick D Goldman, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Jeffrey R Andolina, Xuerong Liu, Roberta E Parrott, Jasmeen Dara, Susan Prockop, Caridad A Martinez, Malika Kapadia, Soma C Jyonouchi, Kathleen E Sullivan, Jack J Bleesing, Sonali Chaudhury, Aleksandra Petrovic, Michael D Keller, Troy C Quigg, Suhag Parikh, Shalini Shenoy, Christine Seroogy, Tamar Rubin, Hélène Decaluwe, John M Routes, Troy R Torgerson, Jennifer W Leiding, Michael A Pulsipher, Donald B Kohn, Linda M Griffith, Elie Haddad, Christopher C Dvorak, Luigi D Notarangelo

Faculty, Staff and Students Publications

Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by …

Thermosensitive And Antioxidant Wound Dressings Capable Of Adaptively Regulating Tgfβ Pathways Promote Diabetic Wound Healing, Hong Niu, Ya Guan, Ting Zhong, Liang Ma, Mohamed Zayed, Jianjun Guan

2020-Current year OA Pubs

Various therapies have been utilized for treating diabetic wounds, yet current regiments do not simultaneously address the key intrinsic causes of slow wound healing, i.e., abnormal skin cell functions (particularly migration), delayed angiogenesis, and chronic inflammation. To address this clinical gap, we develop a wound dressing that contains a peptide-based TGFβ receptor II inhibitor (PTβR2I), and a thermosensitive and reactive oxygen species (ROS)-scavenging hydrogel. The wound dressing can quickly solidify on the diabetic wounds following administration. The released PTβR2I inhibits the TGFβ1/p38 pathway, leading to improved cell migration and angiogenesis, and decreased inflammation. Meanwhile, the PTβR2I does not interfere with …

Proteome Wide Association Studies Of Lrrk2 Variants Identify Novel Causal And Druggable Proteins For Parkinson's Disease, Bridget Phillips, Daniel Western, Lihua Wang, Jigyasha Timsina, Yichen Sun, Priyanka Gorijala, Chengran Yang, Anh Do, Niko-Petteri Nykänen, John C Morris, Suzanne E Schindler, Anne M Fagan, Joel S Perlmutter, Laura Ibanez, Richard J Perrin, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Common and rare variants in the LRRK2 locus are associated with Parkinson's disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of …

Development Of A Covid-19 Vulnerability Index (Cvi) For The Counties And Residents Of New Jersey, Usa., Remo Disalvatore, Sarah K Bauer, Jeong Eun Ahn, Kauser Jahan

Henry M. Rowan College of Engineering Departmental Research

The coronavirus disease 2019, or COVID-19, has impacted countless aspects of everyday life since it was declared a global pandemic by the World Health Organization in March of 2020. From societal to economic impacts, COVID-19 and its variants will leave a lasting impact on our society and the world. During the height of the pandemic, it became increasingly evident that indices, such as the Center for Disease Control's (CDC) Social Vulnerability Index (SVI), were instrumental in predicting vulnerabilities within a community. The CDC's SVI provides important estimates on which communities will be more susceptible to 'hazard events' by compiling a …

A Short Report On The Impact Of Judo On Behaviors And Social Skills Of Children With Autism Spectrum Disorder., Blake S. Lockard, Marissa Dallara, Chasity O'Malley

HPD Articles

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by communication difficulty and social deficits. The current treatment employs the use of psychosocial therapy and medication as well as alternative treatments. This is a pilot study that assessed whether participation in judo improved behavior and social skills in children with ASD.

METHODS: Twenty-four students from the Riverside Youth Judo Club were included in the study, after obtaining consent from their parents to participate. Inclusion criteria included participation in judo classes for more than one month and diagnosis of ASD and/or a developmental disability. Parent(s) of the children signed a …

Intensity Modulated Bolus Electron Conformal Therapy (Im-Bect): Methods For Quality Assurance Of Prime Intensity Modulators And Evaluation Of Planned Im-Bect Dose Distributions, Andrew S. Mcguffey

LSU Doctoral Dissertations

Purpose: Intensity-modulated bolus electron conformal therapy (IM-BECT) shapes homogeneous dose distributions to superficial, irregularly-shaped target volumes, avoiding nearby critical structures. This dissertation provides research useful for translating IM-BECT to the radiotherapy clinic by: (1) developing and testing a factory quality assurance (QA) method for fabricated Passive Radiotherapy Intensity Modulator for Electrons (PRIME) devices and (2) verifying an IM-BECT planning and delivery process using end-to-end tests.

Methods: The IM-BECT planning and delivery process determines beam parameters and treatment devices (cutout, bolus, PRIME device) using .decimal’s (Sanford, FL) ElectronRT (eRT) planning system; calculates dose using a pencil-beam redefinition algorithm modified for PRIME …

Structural Insights Into Rna Bridging Between Hiv-1 Vif And Antiviral Factor Apobec3g, Takahide Kouno, Satoshi Shibata, Megumi Shigematsu, Jaekyung Hyun, Tae Gyun Kim, Hiroshi Matsuo, Matthias Wolf

Computational Medicine Center Faculty Papers

Great effort has been devoted to discovering the basis of A3G-Vif interaction, the key event of HIV's counteraction mechanism to evade antiviral innate immune response. Here we show reconstitution of the A3G-Vif complex and subsequent A3G ubiquitination in vitro and report the cryo-EM structure of the A3G-Vif complex at 2.8 Å resolution using solubility-enhanced variants of A3G and Vif. We present an atomic model of the A3G-Vif interface, which assembles via known amino acid determinants. This assembly is not achieved by protein-protein interaction alone, but also involves RNA. The cryo-EM structure and in vitro ubiquitination assays identify an adenine/guanine base …

The Relationship Between Changes In Neighborhood Physical Environment And Changes In Physical Activity Among Children: A Prospective Cohort Study, Francesco Acciai, Robin S Deweese, Kristen Lloyd, Michael J Yedidia, Michelle Kennedy, Katherine Isselmann Disantis, David Tulloch, Punam Ohri-Vachaspati

College of Population Health Faculty Papers

BACKGROUND: Physical activity (PA) is associated with positive health outcomes over the entire life course. Many community-based interventions that promote PA focus on implementing incremental changes to existing facilities and infrastructure. The objective of this study was to determine if such upgrades were associated with increases in children's PA.

METHODS: Two cohorts of 3- to 15-year-old children (n = 599) living in 4 low-income New Jersey cities were followed during 2- to 5-year periods from 2009 to 2017. Data on children's PA were collected at 2 time points (T1 and T2) from each cohort using telephone survey of parents; data …

Opportunistic Detection Of Type 2 Diabetes Using Deep Learning From Frontal Chest Radiographs, Ayis Pyrros, Stephen M. Borstelmann, Ramana Mantravadi, Zachary Zaiman, Kaesha Thomas, Brandon Price, Eugene Greenstein, Nasir Siddiqui, Melinda Willis, Ihar Shulhan, John Hines-Shah, Jeanne M. Horowitz, Paul Nikolaidis, Matthew P. Lungren, Jorge Mario Rodríguez-Fernández, Judy Wawira Gichoya, Sanmi Koyejo, Adam E. Flanders, Nishith Khandwala, Amit Gupta, John W. Garrett, Joseph Paul Cohen, Brian T. Layden, Perry J. Pickhardt, William Galanter

Department of Radiology Faculty Papers

Deep learning (DL) models can harness electronic health records (EHRs) to predict diseases and extract radiologic findings for diagnosis. With ambulatory chest radiographs (CXRs) frequently ordered, we investigated detecting type 2 diabetes (T2D) by combining radiographic and EHR data using a DL model. Our model, developed from 271,065 CXRs and 160,244 patients, was tested on a prospective dataset of 9,943 CXRs. Here we show the model effectively detected T2D with a ROC AUC of 0.84 and a 16% prevalence. The algorithm flagged 1,381 cases (14%) as suspicious for T2D. External validation at a distinct institution yielded a ROC AUC of …

Mitophagy Promotes Resistance To Bh3 Mimetics In Acute Myeloid Leukemia, Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis

Faculty, Staff and Student Publications

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 …

Using Predictive Validity To Compare Associations Between Brain Damage And Behavior, John F Magnotti, Jaclyn S Patterson, Tatiana T Schnur

Faculty, Staff and Student Publications

Lesion-behavior mapping (LBM) provides a statistical map of the association between voxel-wise brain damage and individual differences in behavior. To understand whether two behaviors are mediated by damage to distinct regions, researchers often compare LBM weight outputs by either the Overlap method or the Correlation method. However, these methods lack statistical criteria to determine whether two LBM are distinct versus the same and are disconnected from a major goal of LBMs: predicting behavior from brain damage. Without such criteria, researchers may draw conclusions from numeric differences between LBMs that are irrelevant to predicting behavior. We developed and validated a predictive …

Comutations And Krasg12c Inhibitor Efficacy In Advanced Nsclc, Marcelo V Negrao, Haniel A Araujo, Giuseppe Lamberti, Alissa J Cooper, Neal S Akhave, Teng Zhou, Lukas Delasos, J Kevin Hicks, Mihaela Aldea, Gabriele Minuti, Jacobi Hines, Jacqueline V Aredo, Michael J Dennis, Turja Chakrabarti, Susan C Scott, Paolo Bironzo, Matthias Scheffler, Petros Christopoulos, Albrecht Stenzinger, Jonathan W Riess, So Yeon Kim, Sarah B Goldberg, Mingjia Li, Qi Wang, Yun Qing, Ying Ni, Minh Truong Do, Richard Lee, Biagio Ricciuti, Joao Victor Alessi, Jing Wang, Blerina Resuli, Lorenza Landi, Shu-Chi Tseng, Mizuki Nishino, Subba R Digumarthy, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Ara A Vaporciyan, George R Blumenschein, Jianjun Zhang, Dwight H Owen, Collin M Blakely, Giannis Mountzios, Catherine A Shu, Christine M Bestvina, Marina Chiara Garassino, Kristen A Marrone, Jhanelle E Gray, Sandip Pravin Patel, Amy L Cummings, Heather A Wakelee, Juergen Wolf, Giorgio Vittorio Scagliotti, Federico Cappuzzo, Fabrice Barlesi, Pradnya D Patil, Leylah Drusbosky, Don L Gibbons, Funda Meric-Bernstam, J Jack Lee, John V Heymach, David S Hong, Rebecca S Heist, Mark M Awad, Ferdinandos Skoulidis

Faculty, Staff and Student Publications

Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, …

Long Covid Clinical Phenotypes Up To 6 Months After Infection Identified By Latent Class Analysis Of Self-Reported Symptoms, Michael Gottlieb, Erica S. Spatz, Huihui Yu, Lauren E Wisk, Joann G. Elmore, Nicole L. Gentile, Mandy Hill, Ryan M. Huebinger, Ahamed H. Idris, Efrat M. Kean, Katherine Koo, Shu-Xia Li, Samuel Mcdonald, Juan Carlos C Montoy, Graham Nichol, Kelli N. O'Laughlin, Ian D. Plumb, Kristin L. Rising, Michelle Santangelo, Sharon Saydah, Ralph C. Wang, Arjun Venkatesh, Kari A. Stephens, Robert A. Weinstein

Department of Emergency Medicine Faculty Papers

BACKGROUND: The prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection.

METHODS: This was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related …

Effect Of Total Population, Population Density And Weighted Population Density On The Spread Of Covid-19 In Malaysia, Hui Shan Wong, Md Zobaer Hasan, Omar Sharif, Azizur Rahman

School of Mathematical & Statistical Sciences Faculty Publications

Since November 2019, most countries across the globe have suffered from the disastrous consequences of the Covid-19 pandemic which redefined every aspect of human life. Given the inevitable spread and transmission of the virus, it is critical to acknowledge the factors that catalyse transmission of the disease. This research investigates the relation of the external demographic parameters such as total population, population density and weighted population density on the spread of Covid-19 in Malaysia. Pearson correlation and simple linear regression were utilized to identify the relation between the population-related variables and the spread of Covid-19 in Malaysia using data from …

Proportion Of Physicians Who Treat Patients With Greater Social And Clinical Risk And Physician Inclusion In Medicare Advantage Networks, Jung Ho Gong, Kenton J Johnston, David J Meyers

2020-Current year OA Pubs

IMPORTANCE: Medicare Advantage (MA) plans are expanding rapidly, now serving 50% of all Medicare enrollees. Little is known about how inclusion rates of physicians in MA plan networks vary by the social and clinical risks of their patients.

OBJECTIVE: To examine the association of physicians caring for patients with higher levels of social and clinical risk in traditional Medicare (TM) with the likelihood of inclusion in MA plan networks.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated the number of patients of physicians participating in TM Part B in 2019. The data analysis was conducted between June 2022 and March …

Membrane Translocation Process Revealed By In Situ Structures Of Type Ii Secretion System Secretins, Zhili Yu, Yaoming Wu, Muyuan Chen, Tong Huo, Wei Zheng, Steven J Ludtke, Xiaodong Shi, Zhao Wang

Faculty, Staff and Students Publications

The GspD secretin is the outer membrane channel of the bacterial type II secretion system (T2SS) which secrets diverse toxins that cause severe diseases such as diarrhea and cholera. GspD needs to translocate from the inner to the outer membrane to exert its function, and this process is an essential step for T2SS to assemble. Here, we investigate two types of secretins discovered so far in Escherichia coli, GspDα, and GspDβ. By electron cryotomography subtomogram averaging, we determine in situ structures of key intermediate states of GspDα and GspDβ in the translocation process, with resolution ranging from 9 Å …

Vitamin B2 Enables Regulation Of Fasting Glucose Availability, Peter M Masschelin, Pradip Saha, Scott A Ochsner, Aaron R Cox, Kang Ho Kim, Jessica B Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L Lorenzi, Alli M Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D Moore, Scott A Summers, Neil J Mckenna, Sean M Hartig

Faculty, Staff and Students Publications

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2-deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPARα, including those required for gluconeogenesis. We also found …

Endothelial Cell Cd36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Transfer And Circulating Fatty Acid Levels, V S Peche, T A Pietka, M Jacome-Sosa, D Samovski, H Palacios, G Chatterjee-Basu, A C Dudley, W Beatty, G A Meyer, I J Goldberg, N A Abumrad

2020-Current year OA Pubs

Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80-100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking …

Cardiovascular Toxicities After Anthracycline And Vegf-Targeted Therapies In Adolescent And Young Adult Cancer Survivors, Jeannette R Wong-Siegel, Robert J Hayashi, Randi Foraker, Joshua D Mitchell

2020-Current year OA Pubs

BACKGROUND: Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood.

OBJECTIVE: This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy.

METHODS: Data were extracted from electronic medical records over a fourteen-year period at a single institution. …

Strength Training: An Inquiry Of Females Perceptions, Laura A. Richardson, Victoria R. Kanel, Alexandria L. Rellinger, Susan E. Ramlo, Carrie L. Fister

Topics in Exercise Science and Kinesiology

Topics in Exercise Science and Kinesiology Volume 4: Issue 1, Article 10, 2023. While traditionally considered a male-dominated activity, women have increasingly embraced strength training. Although strength training has numerous physical and mental benefits to women, their subjective decision-making about using strength training have not been investigated thoroughly, especially using a unique methodology, Q, that is designed specifically to study subjectivity such as viewpoints and decision-making. There is limited research focused on females’ viewpoints about strength training. Capturing feelings and perceptions females have towards resistance training in an objective manner requires a specialized, mixed method called Q methodology [Q] that …

Incidence And Risk Factors For Chylothorax After Pediatric Heart Surgeries: Retrospective Analysis Of A Large Institution Database​, ​Muhammad Shahzad, Yasser Abdulrhman Alheraish, ​​Bushra ​ Algethami, ​​Patricia ​ Machado, Reem Mohamed Essa Beheri, Gamal Mohamed, Fared Khouqeer, Zohair Al Halees

Journal of the Saudi Heart Association

Background: Risk factors for postoperative chylothorax in children who had cardiothoracic procedures are not always clear. Due to complex course in post-operative care, It’s always challenging to find the risk factors, and their management. Objective: The aim of our study was to identify the incidence, risk factors and effective treatment approaches for chylothorax after pediatric heart surgery. Methods: Children who had the cardiac surgery and subsequently developed chylothorax were included in the study. The ratio of the experimental group to the control group was 1:2. Decannulations of extracorporeal membrane oxygenation (ECMO) were not included in the analysis of patient outcomes. …

Medical School Watercooler Newsletter - July 6, 2023, Lindsey Lyle

Watercooler Newsletter

This is the July 6, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents include:

• Pathology residents present research at annual forum
• Basic medical sciences student wins travel award to national conference
• Fellowship-trained gastroenterologist joins internal medicine faculty
• Neurology resident elected to roles at national and state level

Michigancovid19outbreakreportcollection, Michigan Department Of Health & Human Services

Michigan COVID-19 Outbreak Reports

This is a zipped file of all the pdfs uploaded to this collection, spanning from 2020-08-20 through 2023-04-27 for the overall outbreak reports, 2020-09-14 through 2022-06-13 for school outbreak reports, and 2022-06-21 through 2023-04-25 for ISD K-12 outbreak reports.

The zip file also includes a comma separated file that lists the metadata for each file, including the file name within the Michigan COVID-19 Outbreak Reports ScholarWorks Collection (ScholarWorksFileTitle), the archived URL (InternetArchiveLink), the description of the file within the Michigan COVID-19 Outbreak Reports ScholarWorks Collection (ScholarWorksAbstract), and any additional comments about the file within the Michigan COVID-19 Outbreak Reports ScholarWorks …

Specialized Late Cingulo-Opercular Network Activation Elucidates The Mechanisms Underlying Decisions About Ambiguity, Jordan E. Pierce, Nathan M. Petro, Elizabeth Clancy, Caterina Gratton, Steven E. Petersen, Maital Neta

Center for Brain, Biology, and Behavior: Faculty Publications

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In …

Michigancovid19vaccinecollection, Michigan Department Of Health & Human Services

Michigan COVID-19 Vaccine Data

This is a zipped file of all the pdfs uploaded to this collection, spanning from 2020-12-16 through 2023-04-26. It also includes a few additional pdfs: 2020-10-16_Michigan_COVIDVaccination_Plan.pdf; 2020-12-13_Michigan_COVIDVaccination_PrioritizationGuidance.pdf; 2020-12-13_Michigan_COVIDVaccine_FAQ.pdf; 2020-12-13_Michigan_COVIDVaccine_Infograph.pdf; 2021-01-21_Michigan_COVIDVaccine_Locations.pdf.

The zip file also includes a comma separated file that lists the metadata for each file, including the file name within the Michigan COVID-19 Vaccine Data ScholarWorks Collection (ScholarWorksFileTitle), the archived URL (InternetArchiveLink), the description of the file within the Michigan COVID-19 Vaccine Data ScholarWorks Collection (ScholarWorksAbstract), and any additional comments about the file within the Michigan COVID-19 Vaccine Data ScholarWorks Collection (ScholarWorksComments).

High-Performing Conductive Hydrogels For Wearable Applications., Hossein Omidian, Sumana Dey Chowdhury

HPD Articles

Conductive hydrogels have gained significant attention for their extensive applications in healthcare monitoring, wearable sensors, electronic devices, soft robotics, energy storage, and human-machine interfaces. To address the limitations of conductive hydrogels, researchers are focused on enhancing properties such as sensitivity, mechanical strength, electrical performance at low temperatures, stability, antibacterial properties, and conductivity. Composite materials, including nanoparticles, nanowires, polymers, and ionic liquids, are incorporated to improve the conductivity and mechanical strength. Biocompatibility and biosafety are emphasized for safe integration with biological tissues. Conductive hydrogels exhibit unique properties such as stretchability, self-healing, wet adhesion, anti-freezing, transparency, UV-shielding, and adjustable mechanical properties, making …