Medicine and Health Sciences Commons^™

Identification Of Atypical Pediatric Diabetes Mellitus Cases Using Electronic Medical Records, Marcela F Astudillo, William E Winter, Liana K Billings, Raymond Kreienkamp, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur

Faculty, Staff and Students Publications

INTRODUCTION: There are no established methods to identify children with atypical diabetes for further study. We aimed to develop strategies to systematically ascertain cases of atypical pediatric diabetes using electronic medical records (EMR).

RESEARCH DESIGN AND METHODS: We tested two strategies in a large pediatric hospital in the USA. Strategy 1: we designed a questionnaire to rule out typical diabetes and applied it to the EMR of 100 youth with diabetes. Strategy 2: we built three electronic queries to generate reports of three atypical pediatric diabetes phenotypes: unknown type, type 2 diabetes (T2D) diagnosed(AbNegT1D).

RESULTS: Strategy 1 identified six cases …

Total Retinal Thickness Is An Important Factor In Evaluating Diabetic Retinal Neurodegeneration, Noor-Us-Sabah Ahmad, Kristen Staggers, Kyungmoo Lee, Nitish Mehta, Amitha Domalpally, Benjamin J Frankfort, Yao Liu, Roomasa Channa

Faculty, Staff and Students Publications

OBJECTIVE: Macular retinal nerve fibre layer (mRNFL) and ganglion cell-inner plexiform layer thickness (GC-IPL) measurements are important markers of diabetic retinal neurodegeneration (DRN). In this cross-sectional study, we aimed to quantify the contribution of total retinal thickness (TRT) and other factors in the variation of mRNFL and GC-IPL thickness among participants with diabetes.

METHODS AND ANALYSIS: We used macular-centred spectral domain-optical coherence tomography scans from participants with diabetes in the UK Biobank. Two multiple linear regression models (prior to and after adjusting for TRT) were used to determine factors associated with mRNFL and GC-IPL thicknesses. A p value of less …

Homozygous Variants In Wdr83os Lead To A Neurodevelopmental Disorder With Hypercholanemia, Scott Barish, Sheng-Jia Lin, Reza Maroofian, Alper Gezdirici, Hamoud Alhebby, Aurélien Trimouille, Marta Biderman Waberski, Tadahiro Mitani, Ilka Huber, Kristian Tveten, Øystein L Holla, Øyvind L Busk, Henry Houlden, Ehsan Ghayoor Karimiani, Mehran Beiraghi Toosi, Reza Shervin Badv, Paria Najarzadeh Torbati, Fatemeh Eghbal, Javad Akhondian, Ayat Al Safar, Abdulrahman Alswaid, Giovanni Zifarelli, Peter Bauer, Dana Marafi, Jawid M Fatih, Kevin Huang, Cassidy Petree, Daniel G Calame, Charlotte Von Der Lippe, Fowzan S Alkuraya, Sami Wali, James R Lupski, Gaurav K Varshney, Jennifer E Posey, Davut Pehlivan

Faculty, Staff and Students Publications

WD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of …

Management Of Aorto-Right Ventricular Fistulas After Tavr, Ricardo Chia, Chamaka Kalutota, Kerry Cao, Steven Douedi, William Chang, Dominic Pinciotti, Mohammad Beizaeipour, Jennifer Joiner, Daniel Ice, Ronald Ross, Richard Kovach, Chunguang Chen, Muhammad Raza

Division of Cardiology Faculty Papers

This clinical case series reviews the diagnosis and management of aorto-right ventricular fistulas post-transcatheter aortic valve replacement, highlighting 3 cases. We emphasize early detection, individualized treatment strategies, and the role of multidisciplinary heart teams in achieving favorable outcomes. Comprehensive imaging and procedural planning are crucial for successful intervention and management of this rare complication.

Validation Of An Artificial Intelligence-Based Prognostic Biomarker In Patients With Oligometastatic Castration-Sensitive Prostate Cancer, Jarey H. Wang, Matthew P. Deek, Adrianna A. Mendes, Yang Song, Amol Shetty, Soha Bazyar, Kim Van Der Eecken, Emmalyn Chen, Timothy N. Showalter, Trevor J. Royce, Tamara Todorovic, Huei-Chung Huang, Scott A. Houck, Rikiya Yamashita, Ana P. Kiess, Daniel Y. Song, Tamara Lotan, Theodore Deweese, Luigi Marchionni, Lei Ren, Amit Sawant, Nicole L. Simone, Alejandro Berlin, Cem Onal, Andre Esteva, Felix Y. Feng, Phuoc T. Tran, Philip Sutera, Piet Ost

Department of Radiation Oncology Faculty Papers

BACKGROUND: There is a need for clinically actionable prognostic and predictive tools to guide the management of oligometastatic castration-sensitive prostate cancer (omCSPC).

METHODS: This is a multicenter retrospective study to assess the prognostic and predictive performance of a multimodal artificial intelligence biomarker (MMAI; the ArteraAI Prostate Test) in men with omCSPC (n = 222). The cohort also included 51 patients from the STOMP and ORIOLE phase 2 clinical trials which randomized patients to observation versus metastasis-directed therapy (MDT). MMAI scores were computed from digitized histopathology slides and clinical variables. Overall survival (OS) and time to castration-resistant prostate cancer (TTCRPC) were …

Evaluation Of Sirtuin 1 As A Predictor Of Cardiovascular Outcomes In Diabetic Patients With Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Michele Santoro, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly …

Failure In A Population: Tauopathy Disrupts Homeostatic Set-Points In Emergent Dynamics Despite Stability In The Constituent Neurons, James N Mcgregor, Clayton A Farris, Sahara Ensley, Aidan Schneider, Leandro J Fosque, Chao Wang, Elizabeth I Tilden, Yuqi Liu, Jianhong Tu, Halla Elmore, Keenan D Ronayne, Ralf Wessel, Kiran Bhaskaran-Nair, David M Holtzman, Keith B Hengen, Et Al.

2020-Current year OA Pubs

Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal …

High Incidence And Geographic Distribution Of Cleft Palate In Finland Are Associated With The Irf6 Gene, Fedik Rahimov, Pekka Nieminen, Priyanka Kumari, Emma Juuri, Tiit Nikopensius, Kitt Paraiso, Jakob German, Antti Karvanen, Mart Kals, Abdelrahman G Elnahas, Juha Karjalainen, Mitja Kurki, Aarno Palotie, Estonian Biobank Research Team, Finngen, Arja Heliövaara, Tõnu Esko, Sakari Jukarainen, Priit Palta, Andrea Ganna, Anjali P Patni, Daniel Mar, Karol Bomsztyk, Julie Mathieu, Hannele Ruohola-Baker, Axel Visel, Walid D Fakhouri, Brian C Schutte, Robert A Cornell, David P Rice

Faculty, Staff and Student Publications

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence …

Volumetric Body Composition Analysis Of The Cancer Genome Atlas Reveals Novel Body Composition Traits And Molecular Markers Associated With Renal Carcinoma Outcomes, Olesya Mironchuk, Andrew L Chang, Farzaneh Rahmani, Kaitlyn Portell, Elena Nunez, Zack Nigogosyan, Da Ma, Karteek Popuri, Vincent Tze Yang Chow, Mirza Faisal Beg, Jingqin Luo, Joseph E Ippolito

2020-Current year OA Pubs

Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric …

Induction Of A Distinct Macrophage Population And Protection From Lung Injury And Fibrosis By Notch2 Blockade, Mayra Cruz Tleugabulova, Meizi Liu, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, …

Understanding The Impact Of Covid-19 On Yoga Instruction: Examining Teaching Methodology, Class Components, And Injury Patterns In The Northeastern Us, Sojung Kim, June Solow, Donald H Lein, Harshvardhan Singh

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVES: This study aimed to examine the impact of COVID-19 on the perspectives of yoga instructors (YIs) regarding teaching methodology, class components, and yoga-related injuries among their clients DESIGN: A cross-sectional design in this study.

SETTING: A total of 407 YIs from Northeastern United States completed a customized, web-based survey.

MAIN OUTCOME MEASURES: Chi-square tests were carried out to determine changes in yoga teaching format before and during the pandemic, as well as the counts of yoga related injuries between face-to-face (FtoF) and online teaching format. Independent t tests were used to compare the characteristics of yoga teaching elements.

RESULTS: …

Multi-Omic Human Pancreatic Islet Endoplasmic Reticulum And Cytokine Stress Response Mapping Provides Type 2 Diabetes Genetic Insights., Eishani K Sokolowski, Romy Kursawe, Vijay Selvam, Redwan M Bhuiyan, Asa Thibodeau, Chi Zhao, Cassandra N Spracklen, Duygu Ucar, Michael L. Stitzel

Faculty Research 2024

Endoplasmic reticulum (ER) and inflammatory stress responses contribute to islet dysfunction in type 2 diabetes (T2D). Comprehensive genomic understanding of these human islet stress responses and whether T2D-associated genetic variants modulate them is lacking. Here, comparative transcriptome and epigenome analyses of human islets exposed ex vivo to these stressors revealed 30% of expressed genes and 14% of islet cis-regulatory elements (CREs) as stress responsive, modulated largely in an ER- or cytokine-specific fashion. T2D variants overlapped 86 stress-responsive CREs, including 21 induced by ER stress. We linked the rs6917676-T T2D risk allele to increased islet ER-stress-responsive CRE accessibility and allele-specific β …

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Alan Braverman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

METHODS AND RESULTS: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ

CONCLUSIONS: Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor-β pathway genes, particularly

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Jennifer R Landes, Wannes Renders, Laura Muiño Mosquera, Julie De Backer, David W Jantzen, Anji T Yetman, Gisela Teixido-Tura, Arturo Evangelista, Richmond Jeremy, Edward G Jones, Shaine Morris, Tam Doan, Maral Ouzonian, Alan Braverman, Guillaume Jondeau, Olivier Milleron, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) …

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

What Makes An Effective Chief Of Pediatric Cardiology: Insights From Chiefs Of North American Pediatric Programs, Michael E. Kim, Wayne Franklin, Anne M. Dubin, Jeffrey J. Kim, Shubhayan Sanatani, R. Krishna Kumar, Shubhika Srivastava, Thomas R. Kimball, Mark Lewin, Joseph Rossano, Colin J. Mcmahon

Department of Medicine Faculty Papers

BACKGROUND: Although the position of a pediatric cardiology chief is often seen as the apex of one's academic career, its roles, responsibilities, and qualifications are not well defined in the literature. This study was done to gain further insight of the role and attributes of a pediatric cardiology chief by surveying those who are currently serving the position across North American centers.

METHODS AND RESULTS: This was a mixed-methods study with a survey given to North American pediatric cardiology chiefs at programs with fellowship training programs. The survey was a semistructured questionnaire that was independently reviewed by 3 cardiologists. Smaller …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica Ryu, Yoshina Gautam, Diana Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David Relman, Ahmed Shibl, Jeevan Bahadur Sherchand, Aashish Jha, Emily Davenport

SKMC Student Presentations and Publications

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Race And Ethnicity, Gender, And Promotion Of Physicians In Academic Medicine, Lauren Clark, Elena Shergina, Nathalia Machado, Taneisha S Scheuermann, Nasrin Sultana, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: The ranks of academic physicians do not reflect the diversity of the US population. To create a diverse and effective medical workforce, it is important to know the extent to which gender, race and ethnicity, and the intersection of these factors are associated with career advancement.

OBJECTIVE: To assess whether race and ethnicity and gender are associated with appointment to or promotion within academic medicine.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Association of American Medical Colleges data on graduates of all US MD-granting medical schools from 1979 to 2019 merged with faculty appointment data since 2000. Data …

Performance Of Risk Models For Antimicrobial Resistance In Adult Patients With Sepsis, M Cristina Vazquez Guillamet, Hanyang Liu, Andrew Atkinson, Victoria J Fraser, Chenyang Lu, Marin H Kollef

2020-Current year OA Pubs

IMPORTANCE: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals.

OBJECTIVE: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. …

Nepali Oral Microbiomes Reflect A Gradient Of Lifestyles From Traditional To Industrialized, Erica P Ryu, Yoshina Gautam, Diana M Proctor, Dinesh Bhandari, Sarmila Tandukar, Meera Gupta, Guru Prasad Gautam, David A Relman, Ahmed A Shibl, Jeevan Bahadur Sherchand, Aashish R Jha, Emily R Davenport

Faculty, Staff and Student Publications

Background: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called "vanishing microbiomes" potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes …

Federally Qualified Health Centers And Performance Of Medicare Accountable Care Organizations, Kun Li, Yucheng Hou, Frank Mcstay, Jonathan Gonzalez-Smith, Robert S Saunders

Faculty, Staff and Student Publications

IMPORTANCE: Federally qualified health centers (FQHCs) have increasingly participated in the Medicare Shared Savings Program (MSSP) accountable care organizations (ACOs), one of the most widespread value-based programs. Although FQHCs may strengthen ACOs' ability to provide affordable care to diverse Medicare beneficiaries, evidence on ACOs' performance by FQHC participation is limited.

OBJECTIVES: To compare beneficiary characteristics, utilization, expenditure, and quality between ACOs with and without FQHC participation and assess changes in ACO performance after including first FQHCs.

DESIGN, SETTING, AND PARTICIPANTS: Using MSSP public use files, this cross-sectional study compared performance of ACOs that always had FQHC participation with ACOs that …

Genetic Risk Factors Underlying White Matter Hyperintensities And Cortical Atrophy, Yash Patel, Jean Shin, Eeva Sliz, Ariana Tang, Aniket Mishra, Rui Xia, Edith Hofer, Hema Sekhar Reddy Rajula, Ruiqi Wang, Frauke Beyer, Katrin Horn, Max Riedl, Jing Yu, Henry Völzke, Robin Bülow, Uwe Völker, Stefan Frenzel, Katharina Wittfeld, Sandra Van Der Auwera, Thomas H Mosley, Vincent Bouteloup, Jean-Charles Lambert, Geneviève Chêne, Carole Dufouil, Christophe Tzourio, Jean-François Mangin, Rebecca F Gottesman, Myriam Fornage, Reinhold Schmidt, Qiong Yang, Veronica Witte, Markus Scholz, Markus Loeffler, Gennady V Roshchupkin, M Arfan Ikram, Hans J Grabe, Sudha Seshadri, Stephanie Debette, Tomas Paus, Zdenka Pausova

Faculty, Staff and Student Publications

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. …

Age-Related Decline In Blood-Brain Barrier Function Is More Pronounced In Males Than Females In Parietal And Temporal Regions, Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial …

Impa1-Derived Inositol Maintains Stemness In Castration-Resistant Prostate Cancer Via Impdh2 Activation, Che-Chia Hsu, Guihua Wang, Chien-Feng Li, Xian Zhang, Zhen Cai, Tingjin Chen, Bo-Syong Pan, Rajesh Kumar Manne, Gagan Deep, Haiwei Gu, Yuzhuo Wang, Danni Peng, Vasudevarao Penugurti, Xiaobo Zhou, Zhigang Xu, Zhongzhu Chen, Ming Chen, Andrew J Armstrong, Jiaoti Huang, Hong-Yu Li, Hui-Kuan Lin

Faculty, Staff and Student Publications

Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance. Notably, conditional Impa1 knockout in the prostate abrogates the pool and properties of PCSCs to orchestrate CRPC progression and prolong the survival of TRAMP mice. IMPA1-derived inositol serves as a cofactor that directly binds to and activates IMPDH2, which synthesizes guanylate nucleotides for maintaining PCSCs with ARlow/- …

The Utilization Of Echocardiography In Children With Staphylococcus Aureus Bacteremia, Richard Bui, Lauren M Sommer, Meghan Walther, Kristina G Hulten, Jesus G Vallejo, Sheldon L Kaplan, J Chase Mcneil

Faculty, Staff and Students Publications

The need for echocardiography in pediatric Staphylococcus aureus bacteremia (SAB) remains uncertain. We reviewed 331 pediatric SAB cases. Nine subjects, all with comorbidities, met the echocardiogram criteria for infective endocarditis (IE). IE was associated with congenital heart disease and prolonged bacteremia, suggesting that echocardiography is unnecessary in most children with SAB.

Nerve Injury Inhibits Oprd1 And Cnr1 Transcription Through Rest In Primary Sensory Neurons, Ashok Subedi, Asieh Etemad, Aadhya Tiwari, Yuying Huang, Biji Chatterjee, Samantha M Mcleod, Yungang Lu, Diangelo Gonzalez, Krishna Ghosh, Mario Sirito, Sanjay K Singh, Elisa Ruiz, Sandra L Grimm, Cristian Coarfa, Hui-Lin Pan, Sadhan Majumder

Faculty, Staff and Students Publications

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and …

Data-Driven Cutoff Selection For The Patient Health Questionnaire-9 Depression Screening Tool, Brooke Levis, Parash Mani Bhandari, Dipika Neupane, Suiqiong Fan, Ying Sun, Chen He, Yin Wu, Ankur Krishnan, Zelalem Negeri, Mahrukh Imran, Danielle B Rice, Kira E Riehm, Marleine Azar, Alexander W Levis, Jill Boruff, Pim Cuijpers, Simon Gilbody, John P A Ioannidis, Lorie A Kloda, Scott B Patten, Roy C Ziegelstein, Daphna Harel, Yemisi Takwoingi, Sarah Markham, Sultan H Alamri, Dagmar Amtmann, Bruce Arroll, Liat Ayalon, Hamid R Baradaran, Anna Beraldi, Charles N Bernstein, Arvin Bhana, Charles H Bombardier, Ryna Imma Buji, Peter Butterworth, Gregory Carter, Marcos H Chagas, Juliana C N Chan, Lai Fong Chan, Dixon Chibanda, Kerrie Clover, Aaron Conway, Yeates Conwell, Federico M Daray, Janneke M De Man-Van Ginkel, Jesse R Fann, Felix H Fischer, Sally Field, Jane R W Fisher, Daniel S S Fung, Bizu Gelaye, Leila Gholizadeh, Felicity Goodyear-Smith, Eric P Green, Catherine G Greeno, Brian J Hall, Liisa Hantsoo, Martin Härter, Leanne Hides, Stevan E Hobfoll, Simone Honikman, Thomas Hyphantis, Masatoshi Inagaki, Maria Iglesias-Gonzalez, Hong Jin Jeon, Nathalie Jetté, Mohammad E Khamseh, Kim M Kiely, Brandon A Kohrt, Yunxin Kwan, Maria Asunción Lara, Holly F Levin-Aspenson, Shen-Ing Liu, Manote Lotrakul, Sonia R Loureiro, Bernd Löwe, Nagendra P Luitel, Crick Lund, Ruth Ann Marrie, Laura Marsh, Brian P Marx, Anthony Mcguire, Sherina Mohd Sidik, Tiago N Munhoz, Kumiko Muramatsu, Juliet E M Nakku, Laura Navarrete, Flávia L Osório, Brian W Pence, Philippe Persoons, Inge Petersen, Angelo Picardi, Stephanie L Pugh, Terence J Quinn, Elmars Rancans, Sujit D Rathod, Katrin Reuter, Alasdair G Rooney, Iná S Santos, Miranda T Schram, Juwita Shaaban, Eileen H Shinn, Abbey Sidebottom, Adam Simning, Lena Spangenberg, Lesley Stafford, Sharon C Sung, Keiko Suzuki, Pei Lin Lynnette Tan, Martin Taylor-Rowan, Thach D Tran, Alyna Turner, Christina M Van Der Feltz-Cornelis, Thandi Van Heyningen, Paul A Vöhringer, Lynne I Wagner, Jian Li Wang, David Watson, Jennifer White, Mary A Whooley, Kirsty Winkley, Karen Wynter, Mitsuhiko Yamada, Qing Zhi Zeng, Yuying Zhang, Brett D Thombs, Andrea Benedetti, Depression Screening Data (Depressd) Phq Group

Faculty, Staff and Students Publications

IMPORTANCE: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

OBJECTIVE: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

DESIGN, SETTING, AND PARTICIPANTS: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 …

Differences In Brain Volume In Military Service Members And Veterans After Blast-Related Mild Tbi: A Limbic-Cenc Study, Emily L Dennis, Jared A Rowland, Carrie Esopenko, Nicholas J Tustison, Mary R Newsome, Elizabeth S Hovenden, Brian B Avants, Jessica Gill, Sidney R Hinds, Kimbra Kenney, Hannah M Lindsey, Sarah L Martindale, Mary Jo Pugh, Randall S Scheibel, Pashtun-Poh Shahim, Robert Shih, James R Stone, Maya Troyanskaya, William C Walker, Kent Werner, Gerald E York, David X Cifu, David F Tate, Elisabeth A Wilde

Faculty, Staff and Students Publications

Importance: Blast-related mild traumatic brain injuries (TBIs), the "signature injury" of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear.

Objective: To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members.

Design, setting, and participants: Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in …

Post-Artesunate Delayed Hemolysis In Pediatric Malaria Patients In The United States, Sesh A Sundararaman, Karen L Hanze Villavicencio, Brianne Roper, Ziyi Wang, Amy K F Davis, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Gail F Shust, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Post-artesunate delayed hemolysis (PADH) occurred in 6 of 24 children treated with artesunate for severe malaria in the United States; however, severe hemolysis requiring hospitalization or transfusion was rare. In children in the United States treated with artesunate, counseling, and symptom monitoring may be preferred to weekly laboratory surveillance for PADH.

Characterization Of Driver Mutations Identifies Gene Signatures Predictive Of Prognosis And Treatment Sensitivity In Multiple Myeloma, Jian-Rong Li, Abinand Krishna Parthasarathy, Aravind Singaram Kannappan, Shahram Arsang-Jang, Jing Dong, Chao Cheng

Faculty, Staff and Students Publications

In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 …