Medical Specialties Commons^™

Evidence Of Neurovascular Water Exchange And Endothelial Vascular Dysfunction In Schizophrenia: An Exploratory Study, Eric L Goldwaser, Danny J J Wang, Bhim M Adhikari, Joshua Chiappelli, Xingfeng Shao, Jiaao Yu, Tong Lu, Shuo Chen, Wyatt Marshall, Alexa Yuen, Mark Kvarta, Yizhou Ma, Xiaoming Du, Si Gao, Osamah Saeedi, Heather Bruce, Patrick Donnelly, Hugh O'Neill, Alan R Shuldiner, Braxton D Mitchell, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND AND HYPOTHESIS: Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood-brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD.

STUDY DESIGN: We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = …

Five-Year Follow-Up Of Keynote-087: Pembrolizumab Monotherapy For Relapsed/Refractory Classical Hodgkin Lymphoma, Philippe Armand, Pier Luigi Zinzani, Hun Ju Lee, Nathalie A Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P Vassilakopoulos, Akihiro Tomita, Bastian Von Tresckow, Margaret A Shipp, Alex F Herrera, Jianxin Lin, Eunhee Kim, Samhita Chakraborty, Patricia Marinello, Craig H Moskowitz

Faculty, Staff and Student Publications

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received …

Prospective Assessment Of Inter-Rater Reliability Of A Neonatal Adverse Event Severity Scale., Thomas Salaets, Thierry Lacaze-Masmonteil, Isamu Hokuto, Cheri Gauldin, Amjad Taha, Anne Smits, Liesbeth Thewissen, Ilse Van Horebeek, Armuchou Shoraisham, Khorshid Mohammad, Manami Suzuki, Shiori Komachi, Kurt Michels, Mark A. Turner, Karel Allegaert, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology …

Early Exposure To Added Sugars Via Infant Formula May Explain High Intakes Of Added Sugars During Complementary Feeding Beyond Maternal Modeling., Adrianne K. Griebel-Thompson, Tera L. Fazzino, Emily Cramer, Rocco A. Paluch, Katherine S. Morris, Kai Ling Kong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Research has shown that early exposure to added sugars from table food is related to increased intake of added sugars in later childhood. The earliest window of exposure to added sugars may be in infancy via infant formula. However, beyond the well-established factors of maternal lifestyle and modeling, there is a lack of research examining how exposure to added sugars from infant formula influences infant/toddler added sugar intakes from table foods and sugar sweetened beverages (SSB).

OBJECTIVE: While accounting factors previously associated with infant/toddler added sugar intakes and maternal SSB consumption (proximal measure of maternal modeling), this study aims …

Seamless Phase Ii/Iii Design: A Useful Strategy To Reduce The Sample Size For Dose Optimization, Liyun Jiang, Ying Yuan

Faculty, Staff and Student Publications

Background: The traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.

Methods: We identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.

Results: Phase II/III dose-optimization …

Heart Failure Burden In Oman As A Mid-East Exemplar Versus Global Perspectives: An Integrative Review, Maryam Alharrasi, Chandrani Isac, Joy Kabasindi Kamanyire

Journal of the Saudi Heart Association

Heart failure (HF), a clinical syndrome caused by a structural and functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and pulmonary congestion. This study intends to investigate the state of heart failure (HF) in Oman and assess it in comparison of global trends. Ten published literatures from the past 20 years were included after a thorough search of databases (Arab World Research Source, EBSCOhost, Medline, and Google Scholar). These studies were reviewed considering the global literature. We have observed an increase in HF cases especially in older adults, over the past two decades in Oman. Acute coronary syndrome …

Clinically Conserved Genomic Subtypes Of Gastric Adenocarcinoma, Yun Seong Jeong, Young-Gyu Eun, Sung Hwan Lee, Sang-Hee Kang, Sun Young Yim, Eui Hyun Kim, Joo Kyung Noh, Bo Hwa Sohn, Seon Rang Woo, Moonkyoo Kong, Deok Hwa Nam, Hee-Jin Jang, Hyun-Sung Lee, Shumei Song, Sang Cheul Oh, Jeeyun Lee, Jaffer A Ajani, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately …

Stem-Like Cd4+T Cells In Perivascular Tertiary Lymphoid Structures Sustain Autoimmune Vasculitis, Yuki Sato, Abhinav Jain, Shozo Ohtsuki, Hirohisa Okuyama, Ines Sturmlechner, Yoshinori Takashima, Kevin-Phu C Le, Melanie C Bois, Gerald J Berry, Kenneth J Warrington, Jörg J Goronzy, Cornelia M Weyand

Faculty, Staff and Student Publications

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4+ T cell population with stem cell-like features. CD4+ T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription …

Strategies For Maintaining Brain Health: The Role Of Stroke Risk Factors Unique To Elderly Women, Melvin E Klegerman, Tao Peng, Shao-Ling Huang, Brion Frierson, Melanie R Moody, Hyunggun Kim, David D Mcpherson

Faculty, Staff and Student Publications

We have conducted a stability study of a complex liposomal pharmaceutical product, Atheroglitatide (AGT), stored at three temperatures, 4, 24, and 37 °C, for up to six months. The six parameters measured were functions of liposomal integrity (size and number), drug payload (loading efficiency), targeting peptide integrity (conjugation efficiency and specific avidity), and echogenicity (ultrasound-dependent controlled drug release), which were considered most relevant to the product's intended use. At 4 °C, liposome diameter trended upward, indicative of aggregation, while liposome number per mg lipid and echogenicity trended downward. At 24 °C, peptide conjugation efficiency (CE) and targeting efficiency (TE, specific …

Computed Tomography Tissue Characterization Of Pediatric Cardiac Tumor, Rafael Zonana Amkie, Amulya Buddhavarapu, Mehul D Patel, Bihong Zhao, Dilachew A Adebo

Faculty, Staff and Student Publications

Little is known about tissue characterization of cardiac tumors by dedicated cardiac computed tomography (CT) protocols in pediatric patients. We report using arterial and delayed CT acquisitions to characterize a large left ventricular free wall tumor in a 12-year-old female with congenital mitral insufficiency and an automatic implantable cardioverter defibrillator. (

Multidisciplinary Team Approach To Reduce Unplanned Extubations In The Nicu: Going Back To Basics, Jessica M. Dalton Bsn, Rn, Ccrn, Andrea Konno Msn, Rn, C-Elbw, Rnc-Nic, Dolores T. Suzansky Msn, Rnc-Nic

Department of Pediatrics

No abstract provided.

Integrating Participant Feedback And Concerns To Improve Community And Individual Level Chemical Exposure Assessment Reports, Samantha M Samon, Michael Barton, Kim Anderson, Abiodun Oluyomi, Melissa Bondy, Georgina Armstrong, Diana Rohlman

Faculty, Staff and Students Publications

BACKGROUND: As exposure assessment has shifted towards community-engaged research there has been an increasing trend towards reporting results to participants. Reports aim to increase environmental health literacy, but this can be challenging due to the many unknowns regarding chemical exposure and human health effects. This includes when reports encompass a wide-range of chemicals, limited reference or health standards exist for those chemicals, and/or incompatibility of data generated from exposure assessment tools with published reference values (e.g., comparing a wristband concentration to an oral reference dose).

METHODS: Houston Hurricane Harvey Health (Houston-3H) participants wore silicone wristbands that were analyzed for 1,530 …

Hiv-1 Vpu Protein Forms Stable Oligomers In Aqueous Solution Via Its Transmembrane Domain Self-Association, Saman Majeed, Lan Dang, Md Majharul Islam, Olamide Ishola, Peter P Borbat, Steven J Ludtke, Elka R Georgieva

Faculty, Staff and Students Publications

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key HIV-1 protein. It has been considered exclusively a single-pass membrane protein. Previous observations show that this protein forms stable oligomers in aqueous solution, but details about these oligomers still remain obscure. This is an interesting and rather unique observation, as the number of proteins transitioning between soluble and membrane embedded states is limited. In this study we made use of protein engineering, size exclusion chromatography, cryoEM and electron paramagnetic resonance (EPR) spectroscopy to better elucidate the nature of the soluble oligomers. …

A Pre-Medical Student’S Reconciliation Of Feminist Narratives Regarding Women’S Health: A Consideration Of Perspectives On Childbirth In The U.S., Laura Clayton

sprinkle: an undergraduate journal of feminist and queer studies

Many feminists argue that one major negative aspect of reproductive healthcare in the U.S. is the common over-medicalization of women during childbirth, including potentially unnecessary procedures such as cesarean-section and episiotomy. As a solution, they advocate for increased involvement of midwives in childbirth practices, as midwives allow women to give birth at home with minimal medical intervention. This paper analyzes the benefits of midwifery as well as the current increased risk associated with homebirth in the U.S. Additionally, it questions the damaging stigma associated with assumptions of cesarean-section as a suboptimal outcome. A false dichotomy has developed in our culture …

The Col27a1 And Col11a1 Gene Variants Are Not Associated With The Susceptibility To Anterior Cruciate Ligament Rupture In Polish Athletes, Zhuo Sun, Aleksandra Bojarczuk, Pawel Cieszczyk

Baltic Journal of Health and Physical Activity

Introduction: Sports injuries are the most common cause of anterior cruciate ligament (ACL) ruptures. Previous research has demonstrated links between some of the COL27A1 and COL11A1 genetic variants and musculoskeletal soft tissue injuries. However, no previous research has investigated the COL27A1 rs1570460 and the COL11A1 rs3753841 in the context of ACL rupture in any population. Thus, our study aimed to assess the association between specific single nucleotide polymorphisms (SNPs), i.e., COL27A1 rs946053 and COL11A1 rs3753841, and the occurrence of ACL injury (ACL-I) in a cohort of Polish athletes. Methods: The study enrolled 233 athletes with ACL-I (161 males and …

The Prevention And Cardiac Rehabilitation Group Of The Saudi Heart Association Recommendations Regarding Establishing A Cardiac Rehabilitation Service, Abdulhalim Jamal Kinsara, Raghdah Aljehani, Jadwiga Wolszakiewicz, Adam Staron, Muteb A. Alsulaimy

Journal of the Saudi Heart Association

Cardiac rehabilitation (CR) is a cornerstone in the secondary prevention of cardiovascular disease (CVD). Comprehensive cardiac rehabilitation has obtained the highest class of recommendation and the level of evidence for the treatment of patients with ST-segment elevation myocardial infarction, after myocardial revascularization, with chronic coronary syndromes, and in patients with heart failure (HF). Comprehensive cardiac rehabilitation should be implemented as soon as possible, be multi-phasic, and adjusted to the individual needs of the patient. CR is still suboptimally used, and many cardiac centers do not have such services (2). The provision of CR services should be based on standards and …

Patient-Reported Outcomes Of Omission Of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial, Helen M Johnson, Heather Lin, Yu Shen, Emilia J Diego, Savitri Krishnamurthy, Wei T Yang, Benjamin D Smith, Vicente Valero, Anthony Lucci, Susie X Sun, Simona F Shaitelman, Melissa P Mitchell, Judy C Boughey, Richard L White, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

IMPORTANCE: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.

OBJECTIVE: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).

DESIGN, SETTING, AND PARTICIPANTS: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Prognostic Evaluation Of Re-Resection For Recurrent Glioblastoma Using The Novel Rano Classification For Extent Of Resection: A Report Of The Rano Resect Group, Philipp Karschnia, Antonio Dono, Jacob S Young, Stephanie T Juenger, Nico Teske, Levin Häni, Tommaso Sciortino, Christine Y Mau, Francesco Bruno, Luis Nunez, Ramin A Morshed, Alexander F Haddad, Michael Weller, Martin Van Den Bent, Juergen Beck, Shawn Hervey-Jumper, Annette M Molinaro, Nitin Tandon, Roberta Rudà, Michael A Vogelbaum, Lorenzo Bello, Oliver Schnell, Stefan J Grau, Susan M Chang, Mitchel S Berger, Yoshua Esquenazi, Joerg-Christian Tonn

Faculty, Staff and Student Publications

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome.

METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were …

Effects Of In Utero Etoh Exposure On 18s Ribosomal Rna Processing: Contribution To Fetal Alcohol Spectrum Disorder, Nune Darbinian, Gary L Gallia, Armine Darbinyan, Ekaterina Vadachkoria, Nana Merabova, Amos Moore, Laura Goetzl, Shohreh Amini, Michael E Selzer

Faculty, Staff and Student Publications

Fetal alcohol spectrum disorders (FASD) are leading causes of neurodevelopmental disability. The mechanisms by which alcohol (EtOH) disrupts fetal brain development are incompletely understood, as are the genetic factors that modify individual vulnerability. Because the phenotype abnormalities of FASD are so varied and widespread, we investigated whether fetal exposure to EtOH disrupts ribosome biogenesis and the processing of pre-ribosomal RNAs and ribosome assembly, by determining the effect of exposure to EtOH on the developmental expression of 18S rRNA and its cleaved forms, members of a novel class of short non-coding RNAs (srRNAs). In vitro neuronal cultures and fetal brains (11–22 …

A Two-Step Transcriptome Analysis Of The Human Heart Reveals Broad And Disease-Responsive Expression Of Ectopic Olfactory Receptors, Sadia Ashraf, O Howard Frazier, Sylvia Carranza, David D Mcpherson, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

G-protein-coupled receptors (GPCRs) are critical regulators of cardiac physiology and a key therapeutic target for the treatment of heart disease. Ectopic olfactory receptors (ORs) are GPCRs expressed in extra-nasal tissues which have recently emerged as new mediators in the metabolic control of cardiac function. The goals of this study were to profile OR gene expression in the human heart, to identify ORs dysregulated by heart failure caused by ischemic cardiomyopathy, and to provide evidence suggestive of a role for those altered ORs in the pathogenesis of heart failure. Left ventricular tissue from heart failure patients (

Epidermal Growth Factor Receptor-Targeted Neoantigen Peptide Vaccination For The Treatment Of Non-Small Cell Lung Cancer And Glioblastoma, Fenge Li, Huancheng Wu, Xueming Du, Yimo Sun, Barbara Nassif Rausseo, Amjad Talukder, Arjun Katailiha, Lama Elzohary, Yupeng Wang, Zhiyu Wang, Gregory Lizée

Faculty, Staff and Student Publications

The epidermal growth factor receptor (EGFR) plays crucial roles in several important biological functions such as embryogenesis, epithelial tissue development, and cellular regeneration. However, in multiple solid tumor types overexpression and/or activating mutations of the EGFR gene frequently occur, thus hijacking the EGFR signaling pathway to promote tumorigenesis. Non-small cell lung cancer (NSCLC) tumors in particular often contain prevalent and shared EGFR mutations that provide an ideal source for public neoantigens (NeoAg). Studies in both humans and animal models have confirmed the immunogenicity of some of these NeoAg peptides, suggesting that they may constitute viable targets for cancer immunotherapies. Peptide …

Percutaneous Dilatational Tracheostomy In A Cardiac Surgical Intensive Care Unit: A Single-Center Experience, Vignesh Vudatha, Yahya Alwatari, George Ibrahim, Tayler Jacobs, Kyle Alexander, Carlos Puig-Gilbert, Walker Julliard, Rachit Dilip Shah

Department of Surgery Faculty Papers

BACKGROUND: A significant proportion of cardiac surgery intensive care unit (CSICU) patients require long-term ventilation, necessitating tracheostomy placement. The goal of this study was to evaluate the long-term postoperative outcomes and complications associated with percutaneous dilatational tracheostomy (PDT) in CSICU patients.

METHODS: All patients undergoing PDT after cardiac, thoracic, or vascular operations in the CSICU between January 1, 2013 and January 1, 2021 were identified. They were evaluated for mortality, decannulation time, and complications including bleeding, infection, and need for surgical intervention. Multivariable regression models were used to identify predictors of early decannulation and the complication rate.

RESULTS: Ninety-three patients …

Multiancestry Analysis Of The Hla Locus In Alzheimer’S And Parkinson’S Diseases Uncovers A Shared Adaptive Immune Response Mediated By Hla-Drb1*04 Subtypes, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar De Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, José María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jürgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Børge G Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puerta, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A Ross, Luis Jose Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Eadb, Gr@Ace Study Group, Degesco Consortium, Demgene, Eadi, Gerad, Asian Parkinson’S Disease Genetics Consortium, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole A Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sánchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje Van Der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D Greicius, Emmanuel Mignot

Faculty, Staff and Students Publications

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. …

Genetic Susceptibility To Cognitive Decline Following Craniospinal Irradiation For Pediatric Central Nervous System Tumors, Austin L Brown, Pagna Sok, Kimberly P Raghubar, Philip J Lupo, Melissa A Richard, Alanna C Morrison, Jun J Yang, Clinton F Stewart, Mehmet Fatih Okcu, Murali M Chintagumpala, Amar Gajjar, Lisa S Kahalley, Heather Conklin, Michael E Scheurer

Faculty, Staff and Student Publications

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.

RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at …

Erythrophagocytosis In Autoimmune Immunoglobulin A-Mediated Hemolysis, Jahnavi Gollamudi, Swapan Kumar Dasgupta, Perumal Thiagarajan

Faculty, Staff and Students Publications

INTRODUCTION: Warm antibody-mediated autoimmune hemolysis (WAIHA) is most often due to immunoglobulin G (IgG) antibodies and is detected by direct antiglobulin test (DAT). However, about 10% cases of hemolytic anemia are DAT negative. Herein, we describe a patient with DAT-negative hemolytic anemia due to an anti-IgA antibody. We investigate if isolated IgA can promote erythrophagocytosis.

METHODS: We isolated patient and control IgA on Jacalin agarose. Isolated IgA was used to sensitize healthy ABO/Rh-matched donor red blood cells (RBC). Antibody binding was examined by flowcytometry. The effect of IgA on erythrophagocytosis was evaluated using Macrophage colony stimulating factor 1 (M-CSF)-differentiated autologous …

Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease, Dillon Shapiro, Kwanghyuk Lee, Jennifer Asmussen, Thomas Bourquard, Olivier Lichtarge

Faculty, Staff and Students Publications

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Trends And Associated Factors Of Hiv, Hcv And Syphilis Infection Among Different Drug Users In The China-Vietnam Border Area: An 11-Year Cross-Sectional Study (2010-2020), Tong Luo, Zhaosen Lin, Zhenxian Wu, Ping Cen, Aidan Nong, Rongye Huang, Jianhua Che, Fengfeng Liang, Yuan Yang, Jie Liu, Li Huang, Jie Cai, Yanyun Ou, Li Ye, Lijuan Bao, Bingyu Liang, Hao Liang

Faculty, Staff and Student Publications

BACKGROUND: Data on recent human immunodeficiency virus (HIV), hepatitis C virus (HCV) and syphilis prevalence among drug users in the Southwest China are sparse despite the high burden of drug use. This study aims at assessing the prevalence trends and related factors of HIV, HCV and syphilis infection among different drug users in the China-Vietnam border area.

METHODS: A continuous cross-sectional survey was conducted among drug users from 2010 to 2020 in the China-Vietnam border area. Chi-square trend tests were used to assess the trend of HIV, HCV and syphilis prevalence and the proportion for drug type used by drug …

Uptake Of Hiv Testing And Its Correlates Among Sexually Experienced College Students In Southwestern, China: A Web-Based Online Cross-Sectional Study, Jinfeng He, Ping Cen, Jiao Qin, Weiao Qin, Xiudong Xu, Yuanhong Yang, Jinglan Wu, Mu Li, Rongjing Zhang, Tong Luo, Zhifeng Lin, Xinju Huang, Chuanyi Ning, Hao Liang, Li Ye, Bin Xu, Bingyu Liang

Faculty, Staff and Student Publications

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) is becoming more common among college students in China. However, latest data on the prevalence and correlates of HIV testing among sexually experienced college students is rarely.

METHODS: An online survey was conducted among college students aged 18 years or older using multistage stratified cluster sampling from 16 colleges. Data on socio-demographic, HIV testing, HIV-related awareness, attitudes, sexual education and behaviors were collected. Propensity score matching (PSM) and logistic regression model were used to identify factors associated with HIV testing.

RESULT: A total of 108,987 students participated the survey, of which 13,201 …