Medicine and Health Sciences Commons^™

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

The Toxicology Investigators Consortium 2023 Annual Report, Adrienne Hughes, Alexandra Amaducci, Sharan L Campleman, Shao Li, Mari Costantini, Meghan B Spyres, Hannah Spungen, Jessica Kent, Alyssa Falise, Rachel Culbreth, Paul M Wax, Jeffery Brent, Kim Aldy, Toxicology Investigators Consortium Study Group

Faculty, Staff and Student Publications

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the …

Late Subsequent Leukemia After Childhood Cancer: A Report From The Childhood Cancer Survivor Study (Ccss), Taumoha Ghosh, Geehong Hyun, Rikeenkumar Dhaduk, Miriam Conces, Michael A Arnold, Rebecca M Howell, Tara O Henderson, Aaron Mcdonald, Leslie L Robison, Yutaka Yasui, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Subsequent short-latency leukemias are well-described among survivors of childhood cancer. However, late (5-14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort.

Methods: Subsequent leukemias, among 25,656 five-year survivors, were self-reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures.

Results: Seventy-seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Optical Genome Mapping Improves The Accuracy Of Classification, Risk Stratification, And Personalized Treatment Strategies For Patients With Acute Myeloid Leukemia, Sanam Loghavi, Qing Wei, Farhad Ravandi, Andres E Quesada, Mark J Routbort, Shimin Hu, Gokce A Toruner, Sa A Wang, Wei Wang, Roberto N Miranda, Shaoying Li, Jie Xu, Courtney D Dinardo, Naval Daver, Tapan M Kadia, Ghayas C Issa, Hagop M Kantarjian, L Jeffrey Medeiros, Guilin Tang

Faculty, Staff and Student Publications

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four …

Interest In And Willingness To Use Prep: A Cross-Sectional Study Of Individuals With Problematic Substance Use Residing In A High Hiv Prevalence Jurisdiction, Angela M Heads, Constanza De Dios, Kaixuan An, Jin H Yoon, Robert Suchting, Adrienne Gilmore-Thomas, Joy M Schmitz

Faculty, Staff and Student Publications

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting …

The Undiagnosed Diseases Network: Characteristics Of Solvable Applicants And Diagnostic Suggestions For Nonaccepted Ones, John J Mulvihill, Laura Findley, Weihong Ni, Janet S Sinsheimer, F Session Cole, Cecilia Esteves, Jonathan A Bernstein, John H Newman, Matthew T Wheeler, Jill R Mokry, Undiagnosed Diseases Network

Faculty, Staff and Students Publications

Purpose: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)?

Methods: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either …

15-Gene Expression Profile And Prame As Integrated Prognostic Test For Uveal Melanoma: First Report Of Collaborative Ocular Oncology Group Study No. 2 (Coog2.1), J William Harbour, Kisha D Piggott, Et Al.

2020-Current year OA Pubs

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and

Early Detection Of Malignant And Premalignant Peripheral Nerve Tumors Using Cell-Free Dna Fragmentomics, R Taylor Sundby, Paul A Jones, Divya Srihari, Amy E Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, John S A Chrisinger, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

PURPOSE: Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.

EXPERIMENTAL DESIGN: cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: …

Adherence To Hygiene Protocols And Doxycycline Therapy In Ameliorating Lymphatic Filariasis Morbidity In An Endemic Area Post-Interruption Of Disease Transmission In Ghana, Linda Batsa Debrah, Philip J Budge, Et Al.

2020-Current year OA Pubs

Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular …

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity In Outcomes Between Use Of Matched Or Mismatched Unrelated Donors, Brian C Shaffer, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 …

Body Mass Index And Postacute Sequelae Of Sars-Cov-2 Infection In Children And Young Adults, Ting Zhou, Chongliang Luo, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear.

OBJECTIVE: To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with …

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …

Long-Term Efficacy And Safety Of Cannabidiol In Patients With Tuberous Sclerosis Complex: 3-Year Results From The Cannabidiol Expanded Access Program, Arie Weinstock, E Martina Bebin, Daniel Checketts, Gary D Clark, Jerzy P Szaflarski, Laurie E Seltzer, Elizabeth A Thiele, Farhad Sahebkar

Faculty, Staff and Students Publications

OBJECTIVE: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.

METHODS: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. …

The Association Between Vaso/Pressin And Adverse Kidney Outcomes In Children And Young Adults Requiring Vasopressors On Continuous Renal Replacement Therapy, Denise C Hasson, Katja M Gist, Jangdong Seo, Erin K Stenson, Aaron Kessel, Taiki Haga, Sara Lafever, Maria Jose Santiago, Matthew Barhight, David Selewski, Zaccaria Ricci, Nicholas J Ollberding, Natalja L Stanski, The Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Disease (We-Rock) Collaborative

Faculty, Staff and Students Publications

OBJECTIVES: Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults.

DESIGN: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study.

SETTING: Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021.

PATIENTS/SUBJECTS: Patients younger than 25 years receiving CRRT for acute kidney injury and/or …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester B B Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia R Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Anne Stevenson, Charles R J C Newton, Dan J Stein, Elizabeth G Atkinson, Emanuel K Mwesiga, Joseph Kyebuzibwa, Lori B Chibnik, Lukoye Atwoli, Mark Baker, Melkam Alemayehu, Rehema M Mwende, Rocky E Stroud, Solomon Teferra, Stella Gichuru, Symon M Kariuki, Zukiswa Zingela, Moffat Nyirenda, Segun Fatumo, Dickens H Akena

Faculty, Staff and Students Publications

IMPORTANCE: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups.

OBJECTIVE: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …

Corticosteroid Burst Therapy In Patients With Acute Heart Failure: Design Of The Cortahf Pilot Study, Gad Cotter, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality …

Continuous Kidney Replacement Therapy And Survival In Children And Young Adults: Findings From The Multinational We-Rock Collaborative, Michelle C Starr, Katja M Gist, Huaiyu Zang, Nicholas J Ollberding, Shanthi Balani, Andrea Cappoli, Eileen Ciccia, Catherine Joseph, Aadil Kakajiwala, Aaron Kessel, Melissa Muff-Luett, María J Santiago Lozano, Matthew Pinto, Stephanie Reynaud, Sonia Solomon, Cara Slagle, Rachana Srivastava, Weiwen V Shih, Tennille Webb, Shina Menon

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival.

STUDY DESIGN: Retrospective multicenter cohort study.

SETTING & PARTICIPANTS: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases).

EXPOSURE: CKRT for acute kidney injury or volume overload.

OUTCOMES: Death before intensive care unit (ICU) discharge.

ANALYTICAL APPROACH: Descriptive …

Awareness Of, Willingness To Use, And Experiences With Pre-Exposure Prophylaxis Among Youth In Nigeria, Titilola Gbaja-Biamila, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria.

METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for …

Treatment Outcomes Among Patients With A Positive Candida Culture Close To Randomization Receiving Rezafungin Or Caspofungin In The Restore Study, Alex Soriano, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before …

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Axatilimab In Recurrent Or Refractory Chronic Graft-Versus-Host Disease, Daniel Wolff, Iskra Pusic, Et Al.

2020-Current year OA Pubs

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.

METHODS: In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg …

Generalized Encoding Of The Relative Subjective Value Of Cognitive Effort In The Dorsal Acc, Jennifer L Crawford, Rachel E Brough, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a …

Association Between Non-Injection Drug Use And Hepatitis C Infection Among Hiv-Negative Men Who Have Sex With Men, Jing Zhao, Charles Green, Christine Markham, Kayo Fujimoto, Alan G Nyitray, Lu-Yu Hwang

Faculty, Staff and Student Publications

Background: Prior research predominantly examined the association between HIV-positive men who have sex with men (MSM) or those using injection drugs and hepatitis C virus (HCV) infection. However, limited attention has been given to understanding the association among HIV-negative MSM who do not inject drugs. This gap leaves apportion of the population unexamined, potentially overlooking important factor that may contribute to the transmission and prevalence of HCV. This study aims to investigate the relationship between non-injection drug use and HCV infection in this population.

Methods: In this cross-sectional study, we analyzed data on 118 MSM who reported use of non-injection …

Variants In Lrrc7 Lead To Intellectual Disability, Autism, Aggression And Abnormal Eating Behaviors, Jana Willim, Weimin Yuan, Anika Lindsey, Omar Itani, Gary A Silverman, Stephen C Pak, Tim Schedl, Et Al.

2020-Current year OA Pubs

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca

Substitution Of A Single Non-Coding Nucleotide Upstream Of Tmem216 Causes Non-Syndromic Retinitis Pigmentosa And Is Associated With Reduced Tmem216 Expression, Samantha Malka, Pooja Biswas, Anne-Marie Berry, Riccardo Sangermano, Mukhtar Ullah, Siying Lin, Matteo D'Antonio, Aleksandr Jestin, Xiaodong Jiao, Mathieu Quinodoz, Lori Sullivan, Jessica C Gardner, Emily M Place, Michel Michaelides, Karolina Kaminska, Omar A Mahroo, Elena Schiff, Genevieve Wright, Francesca Cancellieri, Veronika Vaclavik, Cristina Santos, Atta Ur Rehman, Sudeep Mehrotra, Hafiz Muhammad Azhar Baig, Muhammad Iqbal, Muhammad Ansar, Luisa Coutinho Santos, Ana Berta Sousa, Viet H Tran, Hiroko Matsui, Anjana Bhatia, Muhammad Asif Naeem, Shehla J Akram, Javed Akram, Sheikh Riazuddin, Carmen Ayuso, Eric A Pierce, Alison J Hardcastle, S Amer Riazuddin, Kelly A Frazer, J Fielding Hejtmancik, Carlo Rivolta, Kinga M Bujakowska, Gavin Arno, Andrew R Webster, Radha Ayyagari

Faculty, Staff and Student Publications

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation …

Different Sensory Information Is Used For State Estimation When Stationary Or Moving., Aaron Wong, Alyssa Eyssalenne, Luke Carter, Amanda S Therrien

Moss-Magee Rehabilitation Papers

The accurate estimation of limb state is necessary for movement planning and execution. While state estimation requires both feedforward and feedback information, we focus here on the latter. Prior literature has shown that integrating visual and proprioceptive feedback improves estimates of static limb position. However, differences in visual and proprioceptive feedback delays suggest that multisensory integration could be disadvantageous when the limb is moving. We formalized this hypothesis by modeling feedback-based state estimation using the long-standing maximum likelihood estimation model of multisensory integration, which we updated to account for sensory delays. Our model predicted that the benefit of multisensory integration …

Intracellular Islatravir-Triphosphate Half-Life Supports Extended Dosing Intervals, Xiaowei Zang, Wendy Ankrom, Walter K. Kraft, Ryan Vargo, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t½) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 …

Social Vulnerability And Sickle Cell Disease Mortality In The Us, Jia Yi Tan, Boon Jian San, Yong-Hao Yeo, Kok Hoe Chan, Hamid S Shaaban, Daniel E Ezekwudo, Modupe Idowu

Faculty, Staff and Student Publications

Importance: Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies.

Objective: To investigate the association of SDOH with SCD mortality rates from 2016 to 2020.

Design, setting, and participants: This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into …

Prognostic Impact Of Notch1 Intracellular Domain, P63, And C-Myc In Lacrimal Gland Adenoid Cystic Carcinoma, Jiawei Zhao, Michelle D Williams, Mike Hernandez, Grace Kuang, Hila Goldberg, Janet Fan, Jing Ning, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

PURPOSE: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC).

METHODS: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC.

RESULTS: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none …