Medical Sciences Commons^™

Substance Use And Outcomes Of Left-Sided Valve Replacement In Patients With Infective Endocarditis, Katie J Hogan, Christopher B Sylvester, Travis J Miles, Matthew Wall, Todd K Rosengart, Marc R Moon, Joseph S Coselli, Subhasis Chatterjee, Ravi K Ghanta

Faculty, Staff and Students Publications

BACKGROUND: Rising rates of substance use (SU) have resulted in an increasing need for left-sided valve surgery for SU-associated infective endocarditis (SU-IE). We compared outcomes, readmissions, and costs between IE patients with and without SU-IE in a national cohort.

METHODS: Using the Nationwide Readmissions Database (2016-2018), we identified 10,098 patients with infective endocarditis (IE) who underwent isolated aortic or mitral valve replacement. Outcomes within the same calendar year as the index operation were compared between patients with and without SU-IE. Multivariable logistic regressions were used to identify factors associated with in-hospital mortality and 30-day and 90-day readmissions. Kaplan-Meier analysis and …

Predicting Operative Mortality In Patients Who Undergo Elective Open Thoracoabdominal Aortic Aneurysm Repair, Kyle W Blackburn, Susan Y Green, Allen Kuncheria, Meng Li, Adel M Hassan, Brittany Rhoades, Scott A Weldon, Subhasis Chatterjee, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Background

We have developed a model aimed at identifying preoperative predictors of operative mortality in patients who undergo elective, open thoracoabdominal aortic aneurysm (TAAA) repair. We converted this model into an intuitive nomogram to aid preoperative counseling.

Methods

We retrospectively analyzed data from 2884 elective, open TAAA repairs performed between 1986 and 2023 in a single practice. Using clinical and selected operative variables, we built 4 predictive models: multivariable logistic regression (MLR), random forest, support vector machine, and gradient boosting machine. Each model’s predictive effectiveness was evaluated with the C-statistic. Test C-statistics were computed using an 80:20 cross-validation scheme with …

Steering Research On Mrna Splicing In Cancer Towards Clinical Translation, Olga Anczukow, Frédéric H-T Allain, Brittany L Angarola, Douglas L Black, Angela N Brooks, Chonghui Cheng, Ana Conesa, Edie I Crosse, Eduardo Eyras, Ernesto Guccione, Sydney X Lu, Karla M Neugebauer, Priyanka Sehgal, Xiao Song, Zuzana Tothova, Juan Valcárcel, Kevin M Weeks, Gene W Yeo, Andrei Thomas-Tikhonenko

Faculty, Staff and Students Publications

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers. Correctly interpreting these molecular fingerprints can reveal novel tumour vulnerabilities and untapped therapeutic opportunities. Yet multiple technological challenges, lingering misconceptions, and outstanding questions hinder clinical translation. …

Rfc2 May Contribute To The Pathogenicity Of Williams Syndrome Revealed In A Zebrafish Model, Ji-Won Park, Tae-Ik Choi, Tae-Yoon Kim, Yu-Ri Lee, Dilan Wellalage Don, Jaya K George-Abraham, Laurie A Robak, Cristina C Trandafir, Pengfei Liu, Jill A Rosenfeld, Tae Hyeong Kim, Florence Petit, Yoo-Mi Kim, Chong Kun Cheon, Yoonsung Lee, Cheol-Hee Kim

Faculty, Staff and Students Publications

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate …

Maturity-Onset Diabetes Of The Young: A Proposal For Updated Nomenclature, Mustafa Tosur

Faculty, Staff and Students Publications

Given the contemporary understanding of diabetes genetics, the term "maturity-onset diabetes of the young (MODY)" warrants renaming. I propose adopting the term "monogenic diabetes" in conjunction with the specific gene name.

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Evaluation Of Stress Ulcer Prophylaxis In Pediatric General Medicine Patients After Transfer From The Intensive Care Unit And At Discharge, Lamees Loubani, Jenna W Bartlett, Brent Mothner, Rathi Asaithambi, Surin Lee

Faculty, Staff and Students Publications

OBJECTIVES: The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU.

METHODS: This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge. Patients were excluded if they were receiving …

10 Practical Priorities To Prevent And Manage Serious Allergic Reactions: Ga2len Anacare And Efa Anaphylaxis Manifesto, Antonella Muraro, Debra De Silva, Marcia Podesta, Aikaterini Anagnostou, Victoria Cardona, Susanne Halken, Pete Smith, Luciana Kase Tanno, Paul Turner, Margitta Worm, Montserrat Alvaro-Lozano, Stefania Arasi, Anna Asarnoj, Simona Barni, Kirsten Beyer, Lucy A Bilaver, Andrew Bird, Roberta Bonaguro, Helen A Brough, R Sharon Chinthrajah, Emma E Cook, Céline Demoulin, Antoine Deschildre, Timothy E Dribin, Motohiro Ebisawa, Montserrat Fernandez-Rivas, Alessandro Fiocchi, David M Fleischer, Eleanor Garrow, Jennifer Gerdts, Mattia Giovannini, Kirsi M Järvinen, Mary Kelly, Edward F Knol, Gideon Lack, Francesca Lazzarotto, Thuy-My Le, Stephanie Leonard, Jay Lieberman, Michael Makris, Lianne Mandelbaum, Mary Jane Marchisotto, Gustavo Andres Marino, Francesca Mori, Caroline Nilsson, Anna Nowak-Wegrzyn, Mikaela Odemyr, H N G Oude Elberink, Kati Palosuo, Nandinee Patel, Jennifer Pier, Sung Poblete, Rima Rachid, Pablo Rodríguez Del Río, Maria Said, Hugh A Sampson, Angel Sánchez Sanz, Sabine Schnadt, Fallon Schultz, Alice Toniolo, Julia E M Upton, Carina Venter, Brian P Vickery, Berber Vlieg-Boerstra, Julie Wang, Graham Roberts, Torsten Zuberbier, Ga2len Anacare Centres And Efa

Faculty, Staff and Students Publications

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient-centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness-raising campaigns for …

Understanding Patients’ Experiences During Transitions From One Electronic Health Record To Another: A Scoping Review, Alison M Cogan, Trenton M Haltom, Stephanie L Shimada, Jessica A Davila, Bryan P Mcginn, Gemmae M Fix

Faculty, Staff and Students Publications

Objectives: Identify existing research on impacts of transitions between electronic health record (EHR) systems on patients' healthcare experiences.

Methods: Scoping review. We searched MedLine, OVID, Embase, CINAHL, and PsycInfo databases for articles on patient experiences with EHR-to-EHR transitions.

Results: Three studies met inclusion criteria. All three used validated surveys to compare patient satisfaction with care pre- and post-transition. The surveys did not include specific questions about the EHR transition; one study focused on patient perceptions of provider computer use. Satisfaction levels initially decreased following EHR implementation, then returned to baseline between six and 15 months later in two of three …

Veterans' Experiences Of And Preferences For Patient-Centered, Measurement-Based Ptsd Care, Marcela C Weber, Ashlyn M Jendro, Ellen P Fischer, Karen L Drummond, Trenton M Haltom, Natalie E Hundt, Michael A Cucciare, Jeffrey M Pyne

Faculty, Staff and Students Publications

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Method: Qualitative interviews were conducted with veterans (n=15) with PTSD who had received at least 2 sessions of a TF-EBP.

Measures: Survey …

Percutaneous Mechanical Aspiration For Infective Endocarditis: Proceedings From An Inaugural Multidisciplinary Summit And Comprehensive Review, Lucas X Marinacci, Sanjum S Sethi, Molly L Paras, Abdallah El Sabbagh, Eric A Secemsky, M Rizwan Sohail, Christoph Starck, Benjamin Bearnot, Evin Yucel, Raymond H M Schaerf, Yasir Akhtar, Ahmad Younes, Marquand Patton, Pedro Villablanca, Seenu Reddy, Daniel Enter, John M Moriarty, William Brent Keeling, Stephanie El Hajj Younes, Charles Kiell, Kenneth Rosenfield

Faculty, Staff and Students Publications

The clinical presentation and epidemiology of infective endocarditis (IE) have evolved over time. While the cornerstones of IE treatment remain antimicrobial therapy and surgery, percutaneous mechanical aspiration (PMA) has emerged as an option for carefully selected patients as a complementary modality, based on retrospective data, case series, and expert experience. In this comprehensive review, we summarize the proceedings from an inaugural summit dedicated to the discussion of PMA in the global management of IE, consisting of experts across multiple disciplines from diverse geographic regions and care environments. After conceptualizing the 3 major roles of PMA as a bridge to decision, …

Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek

Faculty, Staff and Students Publications

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, …

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …

Veno-Arterial Partial Pressure Of Carbon Dioxide Difference As A Metric Of Systemic Oxygen Delivery: Insights From A Correlative Meta-Analysis, Rohit S Loomba, Juan S Farias, Fabio Savorgnan, Sebastian Acosta, Saul Flores, Enrique G Villarreal

Faculty, Staff and Students Publications

The assessment of cardiac output and adequacy of systemic oxygen delivery in children after cardiac surgery require the use of an aggregate of hemodynamic monitors and blood tests. There are previously published data regarding the utility of the veno-arterial partial pressure of carbon dioxide difference (AVDco2) to help with this. This study pooled data on the correlation of AVDco2 with other metrics of cardiac output and systemic oxygen delivery such as arteriovenous oxygen saturation difference, venous saturation, and serum lactate. A systematic review of the literature was done to identify studies analyzing the correlation of AVDco2 with other hemodynamic and …

Systemic Sirolimus Therapy Is Associated With Reduced Intervention Frequency In Pulmonary Vein Stenosis, Alyssa B Kalustian, Joseph L Hagan, Paige E Brlecic, Ionela Iacobas, Rachel D Vanderlaan, Joseph Burns, Thao T Wu, Ravi Birla, Sharada Gowda, Manish Bansal, Srinath T Gowda, Lindsay F Eilers, Asra Khan, Juan Pablo Sandoval-Jones, Michiaki Imamura, Yishay Orr, Christopher A Caldarone, Athar M Qureshi

Faculty, Staff and Students Publications

BACKGROUND: Early clinical outcomes data for adjunctive systemic sirolimus therapy (SST) for moderate to severe pediatric pulmonary vein stenosis (PVS) are promising but limited.

OBJECTIVES: The authors aimed to characterize a cohort of patients treated with SST to determine if SST was associated with a reduction in frequency of PVS interventions.

METHODS: Medical records of 45 patients with PVS treated with SST for ≥1 month from 2015 to 2022 were retrospectively reviewed. PVS intervention rates pre-SST and on-SST were compared using generalized Poisson mixed models, accounting for paired intervals within each patient. In addition to an unadjusted model, an adjusted …

Bst2 Facilitates Activation Of Hematopoietic Stem Cells Through Erk Signaling, Marcus A Florez, Apoorva Thatavarty, Duy T Le, Holly A Hill, Youngjae Jeong, Brian M Ho, Pawel Kus, Trisha K Wathan, Bailee N Kain, Shixia Huang, Dongsu Park, Katherine Y King

Faculty, Staff and Students Publications

The proinflammatory cytokine interferon-gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, as it is induced upon interferon stimulation and required for interferon-dependent HSC activation. To identify the mechanism by which BST2 promotes interferon-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knock out (KO) of BST2 in a murine model does not disrupt …

Osteogenesis Imperfecta: Skeletal And Non-Skeletal Challenges In Adulthood, Jannie Dahl Hald, Bente Langdahl, Lars Folkestad, Lena Lande Wekre, Riley Johnson, Sandesh C S Nagamani, Cathleen Raggio, Stuart H Ralston, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a Mendelian connective tissue disorder associated with increased bone fragility and other clinical manifestations most commonly due to abnormalities in production, structure, or post-translational modification of type I collagen. Until recently, most research in OI has focused on the pediatric population and much less attention has been directed at the effects of OI in the adult population. This is a narrative review of the literature focusing on the skeletal as well as non-skeletal manifestations in adults with OI that may affect the aging individual. We found evidence to suggest that OI is a systemic disease which …

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Families’ Experiences Accessing Care After Genomic Sequencing In The Pediatric Cancer Context: “It’S Just Been A Big Juggle”, Blake Vuocolo, Amanda M Gutierrez, Jill O Robinson, Alva M Recinos, Lauren R Desrosiers, Mary A Majumder, Juan Carlos Bernini, Jonathan Gill, Timothy Griffin, Gail E Tomlinson, Kelly Vallance, Amy L Mcguire, D Williams Parsons, Sharon E Plon, Sarah Scollon

Faculty, Staff and Students Publications

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing …

Hands-On Training About Data Clustering With Orange Data Mining Toolbox, Janez Demšar, Blaž Zupan

Faculty, Staff and Students Publications

Data clustering is a core data science approach widely used and referenced in the scientific literature. Its algorithms are often intuitive and can lead to exciting, insightful results that are easy to interpret. For these reasons, data clustering techniques could be the first method encountered in data science training. This paper proposes a hands-on approach to data clustering training suitable for introductory courses. The education approach features problem-based training that starts with the data and gradually introduces various data processing and analysis methods, illustrating them through visual representations of data and models. The proposed training is suitable for a general …

The Clinical Efficacy And Safety Of Bempedoic Acid In Patients At Elevated Risk Of Cardiovascular Disease: A Meta-Analysis Of Randomized Clinical Trials, Ahmed Sayed, Omar Shazly, Leandro Slipczuk, Chayakrit Krittanawong, Farhala Baloch, Salim S Virani

Faculty, Staff and Students Publications

Purpose: Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent.

Methods: We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I2 measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version …

Aging-Associated Mechanisms Of Atrial Fibrillation Progression And Their Therapeutic Potential, Shuai Zhao, Aaron M Johnston, Chi Him Kendrick Yiu, Lucia M Moreira, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.

Cardiovascular Disease Risk In South Asians In The Baylor Scott And White Health Dilwale Registry, Anandita Agarwala, Priyanka Satish, Tsung-Wei Ma, Preethi Ravindranathan, Aashna Vajramani, Noah Balarbar, Charles Brumley, Abhishek Gami, Khurram Nasir, Vijay Nambi, Javed Butler, Jaideep Patel

Faculty, Staff and Students Publications

Background: Despite implementation of preventive interventions targeting cardiovascular disease (CVD), atherosclerotic CVD (ASCVD) remains a major public health concern in the South Asian (SA) population.

Objectives: The purpose of this study was to assess the risk factor prevalence and ASCVD outcomes in SA population in the United States.

Methods: The DIL Wellness and Arterial health Longitudinal Evaluation registry collected data retrospectively on SA adult patients receiving care in the Baylor Scott & White Healthcare system. Overall and sex stratified analyses were performed to assess the prevalence of traditional CVD risk factors and adverse ASCVD events.

Results: A total of 31,781 …

Health Implications Of Racial Differences In Serum Growth Differentiation Factor Levels Among Men With Obesity, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Elliot Ballato, Georgia Colleluori, Maryam Tetlay, Dennis Tan Villareal, Sanjay Mediwala, Rui Chen, Clifford Qualls, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Growth differentiation factor (GDF15) has been considered a biomarker and recently a hormonal driver for diseases in different populations. However, the role of GDF15 as a biomarker of health outcomes in obese men from different racial/ethnic background has not been evaluated. The objective of this study was to investigate the racial/ethnic differences on the relationship between GDF15 and markers of glucometabolic status, hormonal profile, body composition and bone mineral density (BMD) in obese men. One hundred ninety-three obese men from diverse racial/ethnic backgrounds were enrolled. BMD and body composition were measured by dual energy X-ray absorptiometry. Serum GDF15, osteocalcin, C-terminal …

Cadasil: A Notch3-Associated Cerebral Small Vessel Disease, Lamei Yuan, Xiangyu Chen, Joseph Jankovic, Hao Deng

Faculty, Staff and Students Publications

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of …

Normative Neuroimaging Library: Designing A Comprehensive And Demographically Diverse Dataset Of Healthy Controls To Support Traumatic Brain Injury Diagnostic And Therapeutic Development, Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R Mccauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas

Faculty, Staff and Students Publications

The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and …

Retinal Ganglion Cell Circuits And Glial Interactions In Humans And Mice, Kang-Chieh Huang, Mohamed Tawfik, Melanie A Samuel

Faculty, Staff and Students Publications

Retinal ganglion cells (RGCs) are the brain's gateway for vision, and their degeneration underlies several blinding diseases. RGCs interact with other neuronal cell types, microglia, and astrocytes in the retina and in the brain. Much knowledge has been gained about RGCs and glia from mice and other model organisms, often with the assumption that certain aspects of their biology may be conserved in humans. However, RGCs vary considerably between species, which could affect how they interact with their neuronal and glial partners. This review details which RGC and glial features are conserved between mice, humans, and primates, and which differ. …

Analysis Of Dna Methylation In Gliomas: Assessment Of Preanalytical Variables, Karol Bomsztyk, Daniel Mar, Oleg Denisenko, Suzanne Powell, Monika Vishnoi, Zheng Yin, Jennifer Delegard, Caroline Hadley, Nitin Tandon, Akash J Patel, Anoop P Patel, Richard G Ellenbogen, Rohan Ramakrishna, Robert C Rostomily

Faculty, Staff and Students Publications

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was …

A Reproducible Pipeline For Parcellation Of The Anterior Limb Of The Internal Capsule, Karianne Sretavan, Henry Braun, Zoe Liu, Daniel Bullock, Tara Palnitkar, Remi Patriat, Jayashree Chandrasekaran, Samuel Brenny, Matthew D Johnson, Alik S Widge, Noam Harel, Sarah R Heilbronner

Faculty, Staff and Students Publications

Background: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions.

Methods: Following algorithm development and refinement, we analyzed 43 …

Maternal Glycemic Status And Longitudinal Fetal Body Composition And Organ Volumes Based On Three-Dimensional Ultrasonography, Kathryn A Wagner, Jessica L Gleason, Zhen Chen, Cuilin Zhang, Stefanie N Hinkle, Dian He, Wesley Lee, Roger B Newman, John Owen, Daniel W Skupski, William A Grobman, Seth Sherman, Fasil Tekola-Ayele, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objective: Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown.

Research design and methods: We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse U.S. singleton pregnancy cohort (2015-2019). Women were diagnosed with GDM, impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Up to five 3D ultrasound scans measured fetal body composition and organ volumes; trajectories were modeled using linear mixed models. Overall and weekly mean differences in fetal 3D trajectories were …