Digital Commons Network^™

Tunneling Nanotube-Like Structures Regulate Distant Cellular Interactions During Heart Formation, Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia-Ling Wu, Hongyan Guo, Trang Le Nu Huyen, Yi Zheng, Zhen-Chuan Fan, Weinian Shou, Robert J Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I Serysheva, Alan R Burns, Leo Q Wan, Bin Zhou, Sylvia M Evans, Mingfu Wu

Faculty, Staff and Student Publications

In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and …

Preoperative Brain Volume Loss Is Associated With Postoperative Delirium In Advanced Heart Failure Patients Supported By Left Ventricular Assist Device, Iván Murrieta-Álvarez, Jacob P Scioscia, José M Benítez-Salazar, Jason Uwaeze, Zicheng Xu, Guangyao Zheng, Shiyi Li, Vladimir Braverman, Carl P Walther, Alexis E Shafii, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Delirium is a common neurological complication in patients with advanced heart failure (ADHF) following left ventricular assist device (LVAD) implantation, significantly impacting recovery. This study aimed to analyze non-contrast computed tomography (CT) scans of the brain in ADHF patients undergoing LVAD implantation to determine the association between pre-existing brain atrophy and postoperative delirium. A study involving 166 ADHF patients was conducted from March 2020 to July 2023. Non-contrast CT scans were analyzed using advanced quantitative neuroimaging techniques before implantation. The primary marker assessed was the lateral ventricle fraction (LVF), with secondary markers including cortical gray matter fraction (cGMF), white matter …

Exploration Of Working Memory Retrieval Stage For Mild Cognitive Impairment: Time-Varying Causality Analysis Of Electroencephalogram Based On Dynamic Brain Networks, Yi Jiang, Zhiwei Guo, Xiaobo Zhou, Ning Jiang, Jiayuan He

Faculty, Staff and Student Publications

Background: Mild Cognitive Impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and Alzheimer's disease (AD). Its management is crucial for it helps intervene and slow the progression of cognitive decline to AD. However, the understanding of the MCI mechanism is not completely clear. As working memory (WM) damage is a common symptom of MCI, this study focused on the core stage of WM, i.e., the memory retrieval stage, to investigate information processing and the causality relationships among brain regions based on electroencephalogram (EEG) signals.

Method: 21 MCI and 20 normal cognitive control (NC) participants …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

Faculty, Staff and Student Publications

Background: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

Methods: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Developing A Novel Index For Individual-Level Social Determinants And Cardiovascular Diseases In The Coronary Artery Risk Development In Young Adults (Cardia) Study, Tao Gao, Yinan Zheng, Brian Joyce, Lei Liu, Lili Liu, Catarina Kiefe, Sarah Forrester, Bing Yu, Ankeet Bhatt, Penny Gordon-Larsen, Donald Lloyd-Jones, Kai Zhang, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDH) have been found to contribute to cardiovascular risk and the development of cardiovascular disease (CVD). However, few studies have examined early-life exposure to SDH and the combined effect of multiple SDH measures on CVD. There is an urgent need to develop an SDH index for use in practice and clinical settings.

METHODS: A total of 3189 participants from the CARDIA Study who had chest CT scans at the year-25 (Y25) visit were included in this study. Personal and parental SDH measures, including education, occupation, income, financial strain, and childhood family environment, were obtained through …

Associations Of Sociodemographic, Clinical Factors And Hla-B Alleles With Enthesitis And Peripheral Arthritis In Patients With Ankylosing Spondylitis, Benjamin Sornrung Naovarat, Lianne Gensler, Michael Ward, Mark Hwang, Amirali Tahanan, Mohammad Hossein Rahbar, Mariko Ishimori, Minjae Lee, Matthew A Brown, Michael H Weisman, John D Reveille

Faculty, Staff and Student Publications

Objectives: Factors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).

Methods: Patients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.

Results: Those with peripheral …

Factors Influencing Cyanoacrylate Tissue Adhesive Outcomes For Corneal Thinning And Perforation, Anjali Om, Anjali Badami, Yuqing Wang, Xiangqin Cui, Soroosh Behshad, Joung Kim, Praneetha Thulasi

2020-Current year OA Pubs

No abstract provided.

Recessive Genetic Contribution To Congenital Heart Disease In 5,424 Probands, Weilai Dong, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands. Rare damaging RGs were estimated to contribute to at least 2.2% of CHD, with greater enrichment among laterality phenotypes (5.4%) versus other subsets (1.4%). Among 108 curated human recessive CHD genes, there were 66 RGs, with 54 in 11 genes with >1 RG, 12 genes with 1 RG, and …

Metabolic Signatures In Adipose Tissue Linking Lipophilic Persistent Organic Pollutant Mixtures To Blood Pressure Five Years After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Douglas I Walker, Brittney O Baumert, Hongxu Wang, Jesse A Goodrich, Sarah Rock, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Scott M Bartell, Stavra Xanthakos, Xiangping Lin, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Michele A La Merill, Erika Garcia, Max T Aung, Sandrah P Eckel, Rob Mcconnell, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Persistent organic pollutants (POPs) are lipophilic environmental contaminants accumulated in the adipose tissue. Weight loss interventions, such as bariatric surgery, can mobilize POPs from adipose tissue into the bloodstream. We hypothesized that this mobilization could contribute to increases in blood pressure among 57 adolescents with severe obesity undergoing bariatric surgery. POPs and metabolic features were measured from visceral adipose tissue collected during surgery using gas and liquid chromatography, coupled with high-resolution mass spectrometry. Blood pressure was assessed at baseline, 6 months, and 5 years post-surgery. We used quantile g-computation to estimate associations of POP mixtures with blood pressure changes. With …

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …

Augmented Expression Of Superoxide Dismutase 2 Mitigates Progression And Rupture Of Experimental Abdominal Aortic Aneurysm, Huimin Yan, Ying Hu, Yang Lyu, Antonina Akk, Angela C Hirbe, Samuel A Wickline, Hua Pan, Elisha D O Roberson, Christine T N Pham

2020-Current year OA Pubs

No abstract provided.

Incidence And Correlates Of High-Grade Chemotherapy-Induced Peripheral Neuropathy In Patients With Lung Cancer, Mitchell S Von Itzstein, Sawsan Rashdan, Suzanne E Dahlberg, David E Gerber, Alan B Sandler, Joan H Schiller, David H Johnson, Yating Wang, Zhuoxin Sun, Suresh S Ramalingam

Faculty, Staff and Student Publications

Background: High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.

Methods: We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic …

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-Of-Life Evaluation And 2-Year Outcomes Of Bmt Ctn 1703., Shernan G Holtan, Javier Bolaños-Meade, Monzr M Al Malki, Juan Wu, Carrie L Kitko, Ran Reshef, Andrew R Rezvani, Brian C Shaffer, Melhem M Solh, Janny M Yao, Lyndsey Runaas, Hany Elmariah, Karilyn T Larkin, Najla El Jurdi, Mahasweta Gooptu, Alison W Loren, Aric C Hall, Amin M Alousi, Omer Jamy, William Clark, Leslie Kean, Ami S Bhatt, Miguel-Angel Perales, Kristy Applegate, Yvonne Adeduni Efebera, Eric Leifer, Richard J Jones, Mary M Horowitz, Deborah Mattila, Wael Saber, Mehdi Hamadani, Michael J Martens

Oncology Articles

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant. PRO scores …

Nad+ Prevents Chronic Kidney Disease By Activating Renal Tubular Metabolism, Bryce A. Jones, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood. Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulated renal PPARα signaling and restored FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing showed …

Multi-Ancestry Transcriptome-Wide Association Studies Of Cognitive Function, White Matter Hyperintensity, And Alzheimer's Disease, Dima L Chaar, Zheng Li, Lulu Shang, Scott M Ratliff, Thomas H Mosley, Sharon L R Kardia, Wei Zhao, Xiang Zhou, Jennifer A Smith

Faculty, Staff and Student Publications

Genetic variants increase the risk of neurocognitive disorders in later life, including vascular dementia (VaD) and Alzheimer's disease (AD), but the precise relationships between genetic risk factors and underlying disease etiologies are not well understood. Transcriptome-wide association studies (TWASs) can be leveraged to better characterize the genes and biological pathways underlying genetic influences on disease. To date, almost all existing TWASs on VaD and AD have been conducted using expression studies from individuals of a single genetic ancestry, primarily European. Using the joint likelihood-based inference framework in Multi-ancEstry TRanscriptOme-wide analysis (METRO), we leveraged gene expression data from European ancestry (EA) …

Comparison Between Maia And Mp-3 In Healthy Subjects And Patients With Diabetes, Diabetic Retinopathy, And Age-Related Macular Degeneration, Anna Marmalidou, Haleema Siddiqui, Muhammad Usman Jamil, Kwang Min Woo, Antonio Yaghy, A. Yasin Alibhai, Hiroyuki Takahashi, Stephanie Kaiser, Keith Effert, Peter Zhao, Shilpa Desai, Christopher Robinson, Jay Duker, Nadia Waheed

SKMC Student Presentations and Publications

PURPOSE: The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.

METHODS: This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to …

Exploring Social Impairment In Those With Opioid Use Disorder: Linking Impulsivity, Childhood Trauma, And The Prefrontal Cortex, Thais Costa Macedo De Arruda, Laura Sinko, Paul Regier, Altona Tufanoglu, Adrian Curtin, Anne M. Teitelman, Hasan Ayaz, Peter F. Cronholm, Anna Rose Childress

College of Nursing Faculty Papers & Presentations

BACKGROUND: Challenges with social functioning, which is a hallmark of opioid use disorder (OUD), are a drawback in treatment adherence and maintenance. Yet, little research has explored the underlying mechanisms of this impairment. Impulsivity and corresponding neural alterations may be at the center of this issue. Childhood adversity, which has been linked to both impulsivity and poorer treatment outcomes, could also affect this relationship. This study explores the relationship between impulsivity, social functioning, and their neural correlates in the prefrontal cortex, while examining the potential moderating effects of childhood trauma in individuals recovering from OUD.

METHODS: Participants with (N = …

Connectome-Based Predictive Modeling Of Ptsd Development Among Recent Trauma Survivors, Ziv Ben-Zion, Alexander J Simon, Matthew Rosenblatt, Nachshon Korem, Or Duek, Israel Liberzon, Arieh Y Shalev, Talma Hendler, Ifat Levy, Ilan Harpaz-Rotem, Dustin Scheinost

Staff and Researcher Publications

Importance: The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments.

Objective: To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors.

Design, setting, and participants: This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative …

Assessment Of The Sensitivity Of A Smartphone App To Assist Patients In The Identification Of Stroke And Myocardial Infarction: Cross-Sectional Study, Amar Dhand, Rama Mangipudi, Anubodh S Varshney, Jonathan R Crowe, Andria L Ford, Nancy K Sweitzer, Min Shin, Samuel Tate, Haissam Haddad, Michael E Kelly, James Muller, Jay S Shavadia

2020-Current year OA Pubs

BACKGROUND: Most people do not recognize symptoms of neurological and cardiac emergencies in a timely manner. This leads to delays in hospital arrival and reduced access to therapies that can open arteries. We created a smartphone app to help patients and families evaluate if symptoms may be high risk for stroke or heart attack (myocardial infarction, MI). The ECHAS (Emergency Call for Heart Attack and Stroke) app guides users to assess their risk through evidence-based questions and a test of weakness in one arm by evaluating finger-tapping on the smartphone.

OBJECTIVE: This study is an initial step in the accuracy …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Just As Expected? Older Adults’ Aging Expectations Are Associated With Subjective Cognition, Nikki Hill, Sakshi Bhargava, Justin Do, Emily Bratlee-Whitaker, Monique Brown, Renata Komalasari, Rachel Wu, Jacqueline Mogle

SKMC Student Presentations and Publications

OBJECTIVES: This study investigated the relationship between older adults' expectations regarding aging and subjective cognition. Specifically, we examined whether the three domains of aging expectations (physical health, mental health, and cognitive function) were associated with two aspects of subjective cognition: current subjective cognition and subjective cognitive decline (SCD).

METHOD: An online survey was conducted among U.S. adults aged 65-90 (N = 581; M_age=71.4, SD ± 4.81; 51% female). Measures included the 12-item Expectations Regarding Aging scale, the 8-item PROMIS Cognitive Abilities scale (current subjective cognition), and the 12-item Everyday Cognition scale (SCD). We used generalized linear models …

Ethnoracial Disparities In Gray Matter Atrophy Are Mediated By Structural Disconnectivity In Multiple Sclerosis, Ahmed Bayoumi, Joseph A Thomas, Breanna R Alonzo, Juan Jimenez, Christopher M Orlando, Carlos A Pérez, Khader M Hasan, Jerry S Wolinsky, John A Lincoln

Faculty, Staff and Student Publications

Objective: To investigate ethnoracial disparities in gray matter (GM) atrophy, the contribution of white matter lesions and consequent structural disconnectivity among patients with multiple sclerosis (MS).

Methods: This retrospective study included 297 patients with MS (pwMS), 98 Hispanic/Latinx (H-MS), 82 non-Hispanic Black (B-MS), and 117 non-Hispanic White (W-MS). GM atrophy was assessed using univariate, voxel-based morphometry, and multivariate techniques, source-based morphometry. Structural disconnectivity secondary to white matter lesions was evaluated using the network modification tool. Mediation analyses explored relationships between ethnoracial groups, white matter lesions, structural disconnectivity, and gray matter atrophy.

Results: B-MS and H-MS generally exhibited greater gray matter …

Training Protocol And Calibration Of The International Caries Detection And Assessment System In A School-Based Clinical Trial Of Elementary School-Age Children, Jose-Miguel Yamal, Dania Mofleh, Ru-Jye Chuang, Mengxi Wang, Kila Johnson, Alejandra Garcia-Quintana, Tolulope Titiloye, Suchitra Nelson, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting.

Methods: ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Genetic Characterization Of A Large Cohort Of Individuals With A Clinical Suspicion Of Hypophosphatasia In The United States., Eric T. Rush, Guillermo Del Angel, Juan Dong, Toby Bates, Robert D. Steiner, Allison Cox

Manuscripts, Articles, Book Chapters and Other Papers

Hypophosphatasia (HPP) is a rare metabolic disease resulting from variants in ALPL, inherited in an either autosomal recessive or autosomal dominant manner. Sponsored clinical ALPL testing was offered in the US for individuals with a clinical suspicion of HPP. Gene variants were assessed to determine the likelihood of identifying disease-causing variants, uncover genotype-phenotype relationships, and for further understanding of ALPL variants in the US HPP population. Variants were detected by Sanger sequencing and classified as pathogenic or likely pathogenic (P/LP; positive test result), variant(s) of uncertain significance (indeterminate test result), benign or likely benign (negative test result), or no variants …

Difference-Makers For Collecting Sexual Orientation And Gender Identity Data In Oncology Settings, Mandi L Pratt-Chapman, Edward J Miech, Megan A Mullins, Shine Chang, Gwendolyn P Quinn, Shail Maingi, Matthew B Schabath, Charles Kamen

Faculty, Staff and Student Publications

Purpose: The purpose of this analysis was to identify key difference-making conditions that distinguish oncology institutions that collect sexual orientation and gender identity (SOGI) data across a sample of American Society of Clinical Oncology (ASCO) members.

Methods: From October to November 2020, an anonymous 54-item web-based survey was distributed to ASCO members. Coincidence analysis was used to identify difference-making conditions for the collection of SOGI data.

Results: ASCO members' responses to just three items consistently distinguished practices that reported collecting both SO and GI data (n = 25) from those who did not (n = 20): (1)."Do you ask your …

Wmh Contributions To Cognitive Impairment: Rationale And Design Of The Diverse Vcid Study, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason Hinman, David K Johnson, Danielle Harvey, Myriam Fornage

Faculty, Staff and Student Publications

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter …

American Association Of Physicists In Medicine (Aapm) Chapter Climate Check: Mixed Methods Analysis Of Survey Responses, Ashley J Cetnar, Ghada Aldosary, Meghan C Koo, Holly Lincoln, Angélica Pérez-Andújar, Surendra Prajapati, Samantha J Simiele, Kristi R G Hendrickson

Faculty, Staff and Student Publications

Introduction: The American Association of Physicists in Medicine (AAPM) recently shared results and recommendations from its first Equity, Diversity, and Inclusion (EDI) Climate Survey, which was designed to assess the climate at the workplace, the AAPM organization, and the AAPM regional chapter level. This work further explores the status of EDI at the regional chapter level.

Methods: AAPM's EDI Survey was distributed to 5500 members and had a response rate of 25%. In the survey, three open-ended comment boxes were provided for feedback, including one for regional AAPM members. Sixty-four percent of respondents indicated they were part of a regional …

Psychometric Evaluation Of The Scleroderma Skin Questionnaire: A Novel Patient-Reported Outcome For Skin Disease In Patients With Systemic Sclerosis, Jeong Min Yu, John M Vanburen, Angela Child, Jessica S Alvey, Lisa A Mandl, Laura C Pinheiro, Shervin Assassi, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Brian Skaug, Virginia D Steen, Elizabeth R Volkmann, Jessica K Gordon

Faculty, Staff and Student Publications

Objective: We aimed to evaluate the psychometric properties of the Scleroderma Skin Questionnaire (SSQ), a novel patient-reported outcome (PRO) to assess systemic sclerosis (SSc)-related skin symptoms.

Methods: Participants were recruited from the SSc Collaborative National Quality and Efficacy Registry (CONQUER). Internal consistency was determined using Cronbach α and McDonald ω total (ωt). The correlation of the SSQ was assessed with the modified Rodnan skin score (mRSS), physician global assessment (PGA), Scleroderma Health Assessment Questionnaire, 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and patient global assessment to assess criterion, convergent, and divergent validity. Correlations were also assessed between patients' self-reported recall …

A Combination Of Low Doses Of Lithium And Valproate Improves Cognitive Outcomes After Mild Traumatic Brain Injury, John B Redell, Mark E Maynard, Michael J Hylin, Kimberly N Hood, Andrea Sedlock, Dragan Maric, Jing Zhao, Anthony N Moore, Badrinath Roysam, Shibani Pati, Pramod K Dash

Faculty, Staff and Student Publications

The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + …