Medicine and Health Sciences Commons^™

Hormonal And Circuit Mechanisms Controlling Female Sexual Behavior, Sayaka Inoue

2020-Current year OA Pubs

Sexual behavior is crucial for reproduction in many animals. In many vertebrates, females exhibit sexual behavior only during a brief period surrounding ovulation. Over the decades, studies have identified the roles of ovarian sex hormones, which peak in levels around the time of ovulation, and the critical brain regions involved in the regulation of female sexual behavior. Modern technical innovations have enabled a deeper understanding of the neural circuit mechanisms controlling this behavior. In this review, I summarize our current knowledge and discuss the neural circuit mechanisms by which female sexual behavior occurs in association with the ovulatory phase of …

Awareness, Access, And Communication: Provider Perspectives On Early Intervention Services For Children With Sickle Cell Disease, Andrew M Heitzer, Erin Macarthur, Mollie Tamboli, Ashley Wilson, Jane S Hankins, Catherine R Hoyt

2020-Current year OA Pubs

PURPOSE: This study aimed to identify determinants influencing the utilization of early intervention services among young children with sickle cell disease (SCD) based on perspectives from medical and early intervention providers.

DESIGN AND METHODS: Early intervention and medical providers from the catchment area surrounding St. Jude Children's Research Hospital and Washington University were recruited (20 total providers). Interviews were completed over the phone and audio recorded. All interviews were transcribed verbatim, coded, and analyzed using inductive thematic analysis.

RESULTS: Three overarching themes were identified from both groups: Awareness (e.g., lack of awareness about the EI system and SCD), Access (e.g., …

Ddr2-Regulated Arginase Activity In Ovarian Cancer-Associated Fibroblasts Promotes Collagen Production And Tumor Progression, Favour A Akinjiyan, Zainab Ibitoye, Peinan Zhao, Leah P Shriver, Gary J Patti, Gregory D Longmore, Katherine C Fuh

2020-Current year OA Pubs

Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, …

Transcription Factor Interactions Explain The Context-Dependent Activity Of Crx Binding Sites, Kaiser J. Loell, Ryan Z. Friedman, Connie A. Myers, Joseph C. Corbo, Barak A. Cohen, Michael A. White

2020-Current year OA Pubs

The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while …

Educating Future Generations Of Surgeons Across Borders: Novel Global Linked Hybrid Live Cadaveric Peripheral Nerve Surgical Training Course, Abdus S Burahee, Liron S. Duraku, Caroline A. Hundepool, Kyle R Eberlin, Amy Moore, Christopher J. Dy, Shalimar Abdullah, Vaikunthan Rajaratnam, J. Michiel Zuidam, Dominic M. Power

2020-Current year OA Pubs

BACKGROUND: This study aimed to evaluate a novel, multi-site, technology-facilitated education and training course in peripheral nerve surgery. The program was developed to address the training gaps in this specialized field by integrating a structured curriculum, high-fidelity cadaveric dissection, and surgical simulation with real-time expert guidance.

METHODS: A collaboration between the Global Nerve Foundation and Esser Masterclass facilitated the program, which was conducted across three international sites. The curriculum was developed by a panel of experienced peripheral nerve surgeons and included both text-based and multimedia resources. Participants' knowledge and skills were assessed using pre- and postcourse questionnaires.

RESULTS: A total …

Responsive Neurostimulation For People With Drug-Resistant Epilepsy And Autism Spectrum Disorder, Madeline C. Fields, Emily A. Johnson, John Zempel, Et Al.

2020-Current year OA Pubs

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System.

METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and …

Everything But The Kitchen Sink: An Analysis Of Bacterial And Chemical Contaminants Found In Syringe Residue From People Who Inject Drugs, John A Wildenthal, Drew J Schwartz, Nathanial S Nolan, Lingxia Zhao, John I Robinson, Erin Jones, Raagini Jawa, Jeffrey P Henderson, Laura R Marks

2020-Current year OA Pubs

BACKGROUND: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

METHODS: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry.

RESULTS: Bacteria were cultured from 58.75% of 160 syringes …

Sc2menetdrug: A Computational Tool To Uncover Inter-Cell Signaling Targets And Identify Relevant Drugs Based On Single Cell Rna-Seq Data, Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David Denardo, William Hawkins, Ryan C. Fields, Fuhai Li

2020-Current year OA Pubs

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling …

A Feasibility Trial Of Skin Surface Motion-Gated Stereotactic Body Radiotherapy For Treatment Of Upper Abdominal Or Lower Thoracic Targets Using A Novel O-Ring Gantry, Kendall Kiser, Joshua Schiff, Eric Laugeman, Taeho Kim, Olga Green, Casey Hatscher, Hyun Kim, Shahed Badiyan, Matthew Spraker, Pamela Samson, Clifford Robinson, Alex Price, Lauren Henke

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: A novel O-ring gantry can deliver stereotactic body radiation therapy (SBRT) with artificial intelligence-facilitated, CT-guided online plan adaptation. It gates mobile targets by optically monitoring skin surface motion. However, this gating solution has not been clinically validated. We conducted a trial to evaluate the feasibility of optical skin surface-guided gating for patients with mobile upper abdominal or lower thoracic malignancies treated with SBRT on this platform (NCT05030454).

MATERIALS AND METHODS: Ten patients who were prescribed SBRT to a thoracic or abdominal target and were capable of breath-hold for at least 17 s enrolled. They received SBRT in …

Sirtuin3 Ensures The Metabolic Plasticity Of Neurotransmission During Glucose Deprivation, Anupama Tiwari, Arsalan Hashemiaghdam, Marissa A Laramie, Dario Maschi, Tristaan Haddad, Marion I Stunault, Carmen Bergom, Ali Javaheri, Vitaly Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in the brain plummets, forcing neurons to utilize alternative fuels. However, the molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate that glucose-deprived neurons activate the CREB and PGC1α transcriptional program, which induces expression of the mitochondrial deacetylase Sirtuin 3 (Sirt3) both in vitro and in vivo. We show that Sirt3 localizes to axonal mitochondria and stimulates mitochondrial oxidative capacity in hippocampal nerve terminals. Sirt3 plays an essential role in sustaining synaptic transmission in the absence of glucose …

Pectoral Muscle Removal In Mammogram Images: A Novel Approach For Improved Accuracy And Efficiency, Simin Chen, Debbie L Bennett, Graham A Colditz, Shu Jiang

2020-Current year OA Pubs

PURPOSE: Accurate pectoral muscle removal is critical in mammographic breast density estimation and many other computer-aided algorithms. We propose a novel approach to remove pectoral muscles form mediolateral oblique (MLO) view mammograms and compare accuracy and computational efficiency with existing method (Libra).

METHODS: A pectoral muscle identification pipeline was developed. The image is first binarized to enhance contrast and then the Canny algorithm was applied for edge detection. Robust interpolation is used to smooth out the pectoral muscle region. Accuracy and computational speed of pectoral muscle identification was assessed using 951 women (1,902 MLO mammograms) from the Joanne Knight Breast …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Samuel Klein, Et Al.

2020-Current year OA Pubs

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

Characterization Of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels In Oligodendrocytes., Kyle A Lyman, Ye Han, Andrew P Robinson, Samuel E Weinberg, Daniel W Fisher, Robert J Heuermann, Reagan E Lyman, Dong Kyu Kim, Andreas Ludwig, Navdeep S Chandel, Mark D Does, Stephen D Miller, Dane M Chetkovich

2020-Current year OA Pubs

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I

Lung Lymphatic Endothelial Cells Undergo Inflammatory And Prothrombotic Changes In A Model Of Chronic Obstructive Pulmonary Disease, Anjali Trivedi, Tyler M Lu, Barbara Summers, Kihwan Kim, Alexander J Rhee, Sean Houghton, Derek E Byers, Raphaël Lis, Hasina Outtz Reed

2020-Current year OA Pubs

The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin …

In Vivo Measurement Of Pediatric Extracorporeal Oxygenator Insensible Losses; A Single Center Pilot Study, Tess L Suttles, John Poe, Tara M Neumayr, Ahmed S Said

2020-Current year OA Pubs

INTRODUCTION: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous

METHODS: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow.

RESULTS AND DISCUSSION: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m

Active Transfer Learning For Audiogram Estimation, Hossana Twinomurinzi, Herman Myburgh, Dennis L Barbour

2020-Current year OA Pubs

Computational audiology (CA) has grown over the last few years with the improvement of computing power and the growth of machine learning (ML) models. There are today several audiogram databases which have been used to improve the accuracy of CA models as well as reduce testing time and diagnostic complexity. However, these CA models have mainly been trained on single populations. This study integrated contextual and prior knowledge from audiogram databases of multiple populations as informative priors to estimate audiograms more precisely using two mechanisms: (1) a mapping function drawn from feature-based homogeneous Transfer Learning (TL) also known as Domain …

Case Report: Long-Term Follow-Up Of Patients Who Received A Fimch Vaccine For Prevention Of Recurrent Urinary Tract Infections Caused By Antibiotic Resistant Enterobacteriaceae: A Case Report Series, Elise Perer, Helen Stacey, Terri Eichorn, Heidi Hughey, Julie Lawrence, Eric Cunningham, Mark O'Neil Johnson, Kevin Bacon, Andrew Kau, Scott J Hultgren, Thomas M Hooton, Jennifer L Harris

2020-Current year OA Pubs

Urinary tract infections (UTI) caused by carbapenem-resistant Enterobacteriaceae (CRE) are considered one of the most urgent health threats to humans according to the Centers for Disease Control (CDC), and the World Health Organization (WHO). A FimCH Vaccine expanded access study is being conducted in patients with a history of antibiotic resistant UTIs who are considered to be at risk for development of CRE UTI. This case series describes the clinical, safety and immunogenicity findings for four participants who received a FimCH four-vaccine series. Participants were followed for 12 months after administration of the fourth vaccine for safety, general health status …

Covid-19 Vaccination In Patients With Inborn Errors Of Immunity Reduces Hospitalization And Critical Care Needs Related To Covid-19: A Usidnet Report, John Mcdonnell, Alexa Michelle Altman Doss, Caroline C. Horner, Dayne H. Voelker, Et Al.

2020-Current year OA Pubs

No abstract provided.

Recruiting A Prospective Community Cohort To Study Alzheimer's Disease And Structural And Social Determinants Of Health Among Adults Racialized As Black: The Arches Cohort, Alexis I B Walker, Jean-Francois Trani, Christian F Banks, Samantha A Murphy, Wenqing Zha, Monique M Williams, Gregory S Day, Yiqi Zhu, Beau M Ances, Carl V Hill, Darrell L Hudson, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study.

METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop.

RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking …

Cognitive And Functional Performance And Plasma Biomarkers Of Early Alzheimer's Disease In Down Syndrome, Emily K Schworer, Beau M Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.

METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and …

Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill

2020-Current year OA Pubs

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study.

Script-Based Implementation Of Automatic Grid Placement For Lattice Stereotactic Body Radiation Therapy, Wesley W Tucker, Thomas R Mazur, Matthew C Schmidt, Jessica Hilliard, Shahed Badiyan, Matthew B Spraker, James A Kavanaugh

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: Spatially fractionated radiation therapy (SFRT) has demonstrated promising clinical response in treating large tumors with heterogeneous dose distributions. Lattice stereotactic body radiation therapy (SBRT) is an SFRT technique that leverages inverse optimization to precisely localize regions of high and lose dose within disease. The aim of this study was to evaluate an automated heuristic approach to sphere placement in lattice SBRT treatment planning.

MATERIALS AND METHODS: A script-based algorithm for sphere placement in lattice SBRT based on rules described by protocol was implemented within a treatment planning system. The script was applied to 22 treated cases and …

Pathfinder: A Novel Graph Transformer Model To Infer Multi-Cell Intra- And Inter-Cellular Signaling Pathways And Communications, Jiarui Feng, Haoran Song, Michael Province, Guangfu Li, Philip R O Payne, Yixin Chen, Fuhai Li

2020-Current year OA Pubs

Recently, large-scale scRNA-seq datasets have been generated to understand the complex signaling mechanisms within the microenvironment of Alzheimer's Disease (AD), which are critical for identifying novel therapeutic targets and precision medicine. However, the background signaling networks are highly complex and interactive. It remains challenging to infer the core intra- and inter-multi-cell signaling communication networks using scRNA-seq data. In this study, we introduced a novel graph transformer model, PathFinder, to infer multi-cell intra- and inter-cellular signaling pathways and communications among multi-cell types. Compared with existing models, the novel and unique design of PathFinder is based on the divide-and-conquer strategy. This model …

Transcriptomic Profiling Of Thymic Dysregulation And Viral Tropism After Neonatal Roseolovirus Infection, Andrei Belean, Eden Xue, Benjamin Cisneros, Elisha D O Roberson, Michael A Paley, Tarin M Bigley

2020-Current year OA Pubs

INTRODUCTION: Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation.

METHODS: In the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study …

Dendritic Cell Subsets And Implications For Cancer Immunotherapy, Michael Y Chen, Felicia Zhang, Simon Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

Dendritic cells (DCs) play a central role in the orchestration of effective T cell responses against tumors. However, their functional behavior is context-dependent. DC type, transcriptional program, location, intratumoral factors, and inflammatory milieu all impact DCs with regard to promoting or inhibiting tumor immunity. The following review introduces important facets of DC function, and how subset and phenotype can affect the interplay of DCs with other factors in the tumor microenvironment. It will also discuss how current cancer treatment relies on DC function, and survey the myriad ways with which immune therapy can more directly harness DCs to enact antitumor …

Pd-L1 Has A Heterogeneous And Dynamic Expression In Gastric Cancer With Implications For Immunopet, Dina Ibrahim, Cristina Simó, Emma L Brown, Shayla Shmuel, Sandeep Surendra Panikar, Alex Benton, Rachel Deweerd, Farrokh Dehdashti, Haeseong Park, Patrícia M R Pereira

2020-Current year OA Pubs

INTRODUCTION: This study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells.

METHODS: Dynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both

RESULTS: Consistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared …

Unmet Patient Needs In Monocarboxylate Transporter 8 (Mct8) Deficiency: A Review, Andrew J Bauer, Bethany Auble, Amy L Clark, Tina Y Hu, Amber Isaza, Kyle P Mcnerney, Daniel L Metzger, Lindsey Nicol, Samuel R Pierce, Richard Sidlow

2020-Current year OA Pubs

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the

Examining Heterogeneity In Dementia Using Data-Driven Unsupervised Clustering Of Cognitive Profiles, Sayantan Kumar, Inez Y. Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Philip R. O. Payne

2020-Current year OA Pubs

Dementia is characterized by a decline in memory and thinking that is significant enough to impair function in activities of daily living. Patients seen in dementia specialty clinics are highly heterogenous with a variety of different symptoms that progress at different rates. Recent research has focused on finding data-driven subtypes for revealing new insights into dementia's underlying heterogeneity, rather than assuming that the cohort is homogenous. However, current studies on dementia subtyping have the following limitations: (i) focusing on AD-related dementia only and not examining heterogeneity within dementia as a whole, (ii) using only cross-sectional baseline visit information for clustering …

Health System Barriers To Hypertension Care In Peru: Rapid Assessment To Inform Organizational-Level Change, Kendra N. Williams, Lindsay J. Underhill, Lisa De Las Fuentes, Elvin H. Geng, Victor G. Davila-Roman, Et Al.

2020-Current year OA Pubs

Traditional patient- and provider-level hypertension interventions have proven insufficient to halt hypertension as the leading cause of morbidity and mortality globally. Systems-level interventions are required to address factors challenging hypertension control across a social ecological framework, an under-studied topic particularly salient in low- and middle-income countries (LMICs) such as Peru. To inform such interventions, we sought to identify key health systems barriers to hypertension care in Puno, Peru. A participatory stakeholder workshop (October 2021) and 21 in-depth interviews (October 2021-March 2022) were conducted with 55 healthcare professionals (i.e., doctors, nurses, midwives, dentists, nutritionists), followed by a deductive qualitative analysis of …

Neurocognitive Outcome In Children With Sickle Cell Disease After Myeloimmunoablative Conditioning And Haploidentical Hematopoietic Stem Cell Transplantation: A Non-Randomized Clinical Trial, Suzanne Braniecki, Shalini Shenoy, Robert C Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes.

OBJECTIVES: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time.

METHODS: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD …