Digital Commons Network^™

Atypical Superotemporal Iris And Retinal Coloboma, Katina N Patterson, Margaret M Reynolds, Gregg T Lueder

2020-Current year OA Pubs

PURPOSE: To report our findings in a patient with an atypical case of supertemporal iris and retinal coloboma, and to assess its systemic associations and potential genetic causes.

OBSERVATIONS: A premature female infant born at 31 weeks gestation presented a left eye superotemporal coloboma affecting both the iris and retina. Systemic abnormalities included a left multicystic kidney, hypoplastic left kidney, atrial septal defect, ventricular septal defect, and mild pulmonary valve stenosis. Whole genome sequencing and mitochondrial deoxyribonucleic acid (DNA) sequencing were performed, and both returned negative results.

CONCLUSIONS AND IMPORTANCE: The absence of genetic findings from the negative results of …

Recent Trends In The Utilization Of Molecular Breast Imaging In The United States, Ria Dave, Lin Gu, Heather V Garrett, Debbie Bennett, Dustin Stwalley, Sydney Singer, Sherwin Chiu, Michelle V Lee

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to assess trends in Molecular Breast Imaging (MBI) utilization among privately insured women in the United States (U.S.) from 2017 to 2022.

METHODS: The utilization of MBI among women aged 25-64 years from January 1, 2017, to December 31, 2022, was obtained using the Merative MarketScan Commercial Database. MBI utilization was captured from the outpatient services file using Current Procedural Terminology (CPT) or Healthcare Common Procedure Coding System (HCPCS) codes for MBI.

RESULTS: During the 6-year retrospective claims analysis, 3024 study-eligible women underwent 3648 MBI exams. The overall trend in MBI utilization was …

Single-Cell Multi-Omic Techniques Highlight The Diverse Composition And Intercellular Interactions Of The Vestibular Schwannoma Tumor Microenvironment, Shree S Pari, Sangami Pugazenthi, Albert H Kim, Bhuvic Patel

2020-Current year OA Pubs

Vestibular schwannomas (VS) are tumors arising from Schwann cells of the vestibulocochlear nerve, often leading to hearing loss, gait imbalance, and other neurological complications. Recently, molecular profiling of VS using bulk and single-cell transcriptional and epigenetic approaches has reshaped our understanding of VS pathogenesis and challenged the long-standing view of VS being molecularly homogeneous. These integrative, multi-omic approaches reveal significant differences within VS and highlight diverse Schwann cell subpopulations and their interactions with the tumor microenvironment. Interestingly, these analyses also uncover 2 molecularly distinct groups of VS, one containing Schwann cells with an "Injury-like" phenotype that drives VS progression through …

Bacterial Immune Activation Via Supramolecular Assembly With Phage Triggers, Tong Zhang, Yifei Lyu, Christina R Beck, Naseer Iqbal, Renee Barbosa, Alireza Ghanbarpour, Michael T Laub

2020-Current year OA Pubs

Bacteria use diverse mechanisms to protect themselves against phages

Comparison Of Variant Callers Using 60 532 Multi-Ancestry Whole Genome Sequences, Hufeng Zhou, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Whole genome sequencing (WGS) studies play a pivotal role in studying the genetic underpinnings of human diseases and traits. High quality and reproducible variant calling is the cornerstone for the success of downstream analyses, including WGS association studies and polygenic risk prediction. This paper compares the data quality, performance, and concordance of two widely used WGS variant callers, the Genome Analysis Toolkit (GATK) and Variant Tool set that discovers short variants (VT), using 60 532 multi-ancestry whole genomes sequenced by the Centers for Common Disease Genomics (CCDGs) of the NHGRI Genome Sequencing Program. Our findings show that both QCed GATK …

Astrocyte-Specific Deletion Of Lrrc8a Causes Neurological Dysfunction But Not Chronic White Matter Edema, Sven Kerst, Leoni Hoogterp, Marjolein Breur, Gemma M Van Rooijen-Van Leeuwen, Marianna Bugiani, Rajan Sah, Huibert D Mansvelder, Marjo S Van Der Knaap, Rogier Min

2020-Current year OA Pubs

Volume-regulated anion channels (VRACs) are central to cell volume homeostasis. They mediate swelling-induced efflux of chloride and organic osmolytes to drive regulatory volume decrease. In the brain, VRACs have been proposed to play a key role in astrocytic volume regulation. Genetic defects in astrocytic VRAC modulating proteins (MLC1, GlialCAM, Aquaporin-4, GPRC5B) cause the leukodystrophy Megalencephalic leukoencephalopathy with subcortical cysts (MLC), characterized by chronic white matter edema and myelin vacuolization. Disrupted VRAC activity in MLC-patient-derived lymphoblasts and primary astrocytes from MLC mice further supports a pathogenic link between defective VRAC activity and MLC. Here, we studied the physiological and pathological consequences …

Increased Clinical Frailty Is Associated With Aortic-Related Mortality Following Fenestrated And Branched Endovascular Repair For Thoracoabdominal Aortic Aneurysm, Silvia Chen, Elizabeth Ramirez, Blake E Murphy, Anjali Sribalaskandarajah, Martin Bunker, Joel Kruger, Karina A Newhall, Rebecca A Sorber, Sara L Zettervall, Matthew P Sweet

2020-Current year OA Pubs

OBJECTIVE: Clinical frailty is associated with reduced long-term survival after fenestrated and branched endovascular aortic repair (F/BEVAR). This study assesses the impact of phenotypic clinical frailty on perioperative outcomes and cause of death following F/BEVAR for thoracoabdominal aortic aneurysm.

METHODS: Patients who underwent F/BEVAR at a single institution from 2012 to 2024 were identified. The clinical frailty scale (CFS) was used to determine phenotypic frailty. Patients with a preoperative CFS of ≥4 (vulnerable) and a CFS of < 4 were compared. We used χ

RESULTS: We included 233 patients; 60 (25.8%) had a CFS of ≥4 and 173 (74.2%) had a CFS of < 4. Patients with a CFS of ≥4 were more likely to have chronic obstructive pulmonary disease (53% vs 27%) and were treated for slightly larger aneurysms (72 mm vs 68 mm; P = .04). There were no differences in symptomatic presentation, aneurysm extent, or operative complexity between patient groups. Additionally, there were no differences in perioperative complications including 30-day mortality, stroke, and spinal cord ischemia. Patients with a CFS of ≥4 had an increased length of hospitalization (11.3 days vs 6.9 days; P < .01) and were less likely to return to preoperative functional status (62.7% vs 86.1%; P < .01). The 3-year all-cause and aortic-related mortality rates were 35.2% and 5.7%, respectively. Patients with a CFS of ≥4 had a lower survival at 1 year (74% vs 89%), 3 years (39% vs 73%), and 5 years (25% vs 56%), compared with patients with a CFS of < 4 (P < .01). The most common causes of death among both groups were pulmonary comorbidities (14.0%), oncologic conditions (14.0%), cardiovascular comorbidities (11.2%), and procedure-related complications (11.2%). Patients with a CFS of ≥4 were more likely to die from aortic-related mortality (10.3% vs 5.9%; P = .02), pulmonary comorbidities (15.4 vs 13.2%; P = .04), systemic decline (7.7% vs 1.5%; P = .02), and infection (12.8% vs 7.4%; P = .03). Aortic-related mortality for the entire patient cohort was 2.2% and 5.7% at 1 year and 3 years, respectively. Aortic-related deaths among clinically frail patients were often due to an inability to tolerate further aortic operations (eg, arch repair), and secondary to follow-up nonadherence in patients with a CFS of < 4.

CONCLUSIONS: In an expanded …

The Win Ratio For Evaluating Edoxaban Vs Dalteparin For Cancer-Associated Venous Thromboembolism: An Analysis Of The Randomized Hokusai Venous Thromboembolism Cancer Trial, Nick Van Es, Luuk J J Scheres, Kristen M Sanfilippo, Harry Büller, Marc Carrier, Marcello Di Nisio, Michael Grosso, Renato D Lopes, William F Mcintyre, Bjorn Redfors, Annelise Segers, Peter Verhamme, Jeffrey I Weitz, Patrick M Bossuyt, Deborah M Siegal

2020-Current year OA Pubs

BACKGROUND: The Hokusai Venous Thromboembolism (VTE) Cancer trial demonstrated that edoxaban was noninferior to dalteparin for the treatment of cancer-associated venous VTE.

OBJECTIVES: We reanalyzed the trial using the win ratio, an approach that evaluates a composite of outcomes in a hierarchical order.

METHODS: Forty-nine thrombosis experts ranked 10 outcomes in order of clinical importance from all-cause death (most important) to clinically relevant nonmajor bleeding (least important). We performed unmatched pairwise comparisons between participants on edoxaban and those on dalteparin at 6- and 12-month follow-up. Within each pair, edoxaban was assigned a win, loss, or tie according to the hierarchy …

Longitudinal Analysis Of Rotator Cuff Repair: Joint Kinematics And Clinical Outcomes, Sujata Khandare, Rebekah L Lawrence, Alena Jalics, Roger Zauel, Vasilios Moutzouros, Eric C Makhni, Stephanie Muh, Michael J Bey

2020-Current year OA Pubs

BACKGROUND: Rotator cuff repair is a common surgical procedure, but postoperative outcomes can be highly variable, and postoperative repair tissue healing remains a significant clinical challenge. Furthermore, the biomechanical effects of rotator cuff repair are not fully understood.

METHODS: Twenty-two participants scheduled for arthroscopic rotator cuff repair were evaluated preoperatively and at 3, 12, and 24 months postsurgery. The following data were recorded at each time point: glenohumeral and scapulothoracic kinematics, shoulder strength, and patient-reported measures of pain and function. Postoperative repair integrity was assessed via magnetic resonance imaging at 3 months and 24 months postsurgery.

RESULTS: At 3 months …

Piezo Mechanosensitivity In Chondrocytes Is Differentially Modulated By L-Type And T-Type Voltage-Sensitive Ion Channels, Alireza Savadipour, Gabrielle K Marushack, Robert J Nims, Jaquelin M Garcia-Castorena, Wolfgang Liedtke, Farshid Guilak

2020-Current year OA Pubs

OBJECTIVE: One of the primary factors contributing to OA development is altered or excessive mechanical stress on the joint, which chondrocytes sense in part through the PIEZO mechanosensitive ion channels. These channels activate signaling pathways that result in joint inflammation and cartilage degeneration. In addition to PIEZO channels, voltage-gated calcium (Ca

DESIGN: To better understand the relationship between PIEZO1 and VGCCs, we quantified porcine chondrocytes' intracellular Ca

RESULTS: In primary chondrocytes, nifedipine, an L-type VGCC blocker, reduced PIEZO1 sensitivity to both mechanical compression and pharmacological agonism, while NNC-55, a T-type VGCC blocker, increased PIEZO1 activation in response to both stimuli. …

Synovial Fibroblast Responses To Different Types Of Injury Resulting In Cartilage Repair Or Osteoarthritis, Fraser L Collins, Alexander J Knights, Tristan Maerz, Anke J Roelofs, Cosimo De Bari

2020-Current year OA Pubs

OBJECTIVE: Single-cell RNA-sequencing (scRNA-seq) has advanced our understanding of the heterogeneity of synovial fibroblasts and their roles in tissue repair and osteoarthritis. Here, we compared the fibroblast responses to different types and duration of joint injury in mice.

DESIGN: Published scRNA-seq data of synovial fibroblasts from a model of joint surface injury (JSI, day 6) and two post-traumatic osteoarthritis models, destabilisation of the medial meniscus (DMM, day 7 and 2 months) and anterior cruciate ligament rupture (ACLR, day 7 and day 28), were integrated and analysed using clustering, DEG, gene-set enrichment, regulon, pseudotime trajectory and cell-cycle analyses.

RESULTS: The response …

From Damage Signals To Immune Modulators: Oxidized Lipids In Immunometabolic Inflammation, Neetu Srivastava, Xiaoxiao Wan

2020-Current year OA Pubs

Oxidized lipids, once viewed as byproducts of oxidative stress, are now recognized as critical mediators linking metabolism, redox imbalance, and immunity. Generated through enzymatic and nonenzymatic oxidation of polyunsaturated fatty acids, oxidized phospholipids, lipid aldehydes, and oxidized lipoproteins act as context-dependent signals regulating immune activation, resolution, and metabolic adaptation. In metabolic inflammation, these lipids engage scavenger and Toll-like receptors to influence macrophage polarization, dendritic-cell function, and T-cell differentiation. Their context and concentration determine whether oxidized lipids amplify inflammation or promote immune tolerance. Accumulation of these species connects oxidative stress to immune dysfunction, contributing to diseases, such as atherosclerosis, obesity, diabetes, …

Patient And Chondral Defect-Specific Characteristics And Associated Matrix-Induced Autologous Chondrocyte Implantation Conversion Rates Following Biopsy, Derrick M Knapik, Daniel C Touhey, S Ryan Pierson, Christopher K Bozorgmehr, Matthew V Smith, Matthew J Matava, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Focal chondral defects in the knee lead to swelling, discomfort, and mechanical symptoms, resulting in disability and loss of function. Matrix-induced autologous chondrocyte implantation (MACI) has emerged as a viable treatment option, with satisfactory clinical outcomes reported compared with microfracture. Patient and lesion-specific variables associated with MACI after biopsy remain largely underreported.

PURPOSE: To examine patient- and defect-specific characteristics associated with conversion to MACI after biopsy from a single institution.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: A retrospective chart review of prospectively collected data from June 2018 to March 2025 was performed. Inclusion criteria included patients …

Trajectories And Predictors Of Activity Participation Among People With Parkinson Disease: A 3-Year Longitudinal Study, Moon Young Kim, Yejin Lee, Carolyn M Baum, Lisa T Connor, Chih-Hung Chang, Linda Tickle-Degnen, Erin R Foster

2020-Current year OA Pubs

OBJECTIVE: To investigate how participation changes over time among individuals with Parkinsondisease (PD) and identify factors influencing these changes, focusing on impairment level and social factors.

DESIGN: Secondary analysis of a 3-year prospective cohort study of social self-management of PD. Data were collected during 4 in-person assessments conducted at baseline and then annually thereafter. Multilevel modeling was used to analyze data from the 4 time points.

SETTING: Department of Occupational Therapy Research Laboratory and Department of Neurology Movement Disorder Clinic.

PARTICIPANTS: A total of 86 individuals (N = 86) with idiopathic PD (Hoehn & Yahr stages I-IV; mean age ± …

Real-World Experience With Selexipag In Patients With Pulmonary Arterial Hypertension: Treatment Patterns And Outcomes Across Baseline Risk Strata (Sphere And Exposure Studies), Pilar Escribano Subias, Murali M Chakinala, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment strategies for pulmonary arterial hypertension (PAH) depend on patients' 1-year mortality risk; however, real-world practices and outcomes remain inadequately described.

OBJECTIVE: We aimed to investigate real-world experience with selexipag, an oral selective prostacyclin I2 receptor agonist used to treat PAH.

METHODS: This analysis of two large, prospective, observational studies: SPHERE (NCT03278002; USA; completed) and EXPOSURE (EUPAS19085; Europe and Canada; ongoing, data cutoff November 2021) included adults newly initiating selexipag with follow-up available.

RESULTS: Of 1366 selexipag users, 894 met eligibility criteria. At selexipag initiation, the median (Q1-Q3) age was 61 (48-70) years and the time since diagnosis was …

Bach2 Regulates T Cell Lineage State To Enhance Car T Cell Function, Tien-Ching Chang, Amanda Heard, John Lattin, John M Warrington, Amanda Barrett, Jack H Landmann, Yangdon Tenzin, Vishaal Ganesh, Bryant Thompson, Sadia Afrin, Deepesh Kumar Gupta, Ju-Fang Chang, Julie Ritchey, Mehmet Emrah Selli, Yu-Sung Hsu, A J Federico, Avery Horn, Michael P Meers, John F Dipersio, Nathan Singh, Et Al.

2020-Current year OA Pubs

Nearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as 'tonic signaling'. Tonic signaling of CARs containing 41BB domains enhances T cell fitness and function, in contrast to the exhaustion driven by CD28-containing CARs. Here we show that 41BB induces BACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 successfully prevented exhaustion but locked CAR T cells in a quiescent state. We linked BACH2 to a degradation domain to tune BACH2, enabling us to prevent exhaustion while enabling potent effector function that broadly enhanced the long-term efficacy of CAR T cells …

Mapping Charge Interactions In Intrinsically Disordered Proteins, Michael Phillips, Andrea Holla, Magdalena Wojtas, Aritra Chowdhury, Andrea Sottini, Sebastian L B König, Natalie Mutter, Nick Lamb, Jonathan Huihui, Monika Lopko, Andrea Soranno, Daniel Nettels, Andrzej Ożyhar, Benjamin Schuler, Kingshuk Ghosh

2020-Current year OA Pubs

Intrinsically disordered proteins (IDPs) are often rich in charged residues, and electrostatic interactions have a pronounced effect on their conformational distributions, interactions and functions. However, attaining quantitative understanding of electrostatics is challenging because of the sequence-specific arrangement of charges in the chain, the long-range nature of electrostatic interactions, charge screening, and the condensation of counterions-effects that all need to be taken into account self-consistently. Here, analytically tractable quantitative models are developed to predict ensemble average distances between any pair of residues in IDPs as a function of sequence and salt concentration, explicitly considering charge patterning. These models are tested systematically …

Durability Of Efficacy, Safety, And Quality Of Life 5 Years After Valoctocogene Roxaparvovec Gene Transfer For Severe Hemophilia A: Final Phase 3 Gener8-1 Trial Results, Andrew D Leavitt, Elaine Majerus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Valoctocogene roxaparvovec, a gene therapy for severe hemophilia A, enables endogenous factor VIII (FVIII) expression and confers bleed control.

OBJECTIVES: To present the final 5-year efficacy and safety results from the phase 3 GENEr8-1 trial.

METHODS: Adult men (

RESULTS: Median follow-up was 261.1 weeks; 128 of 134 participants completed the study. For the 112 participants who enrolled from a previous noninterventional study (rollover population), mean ABR for treated bleeds declined by 83.3% (

CONCLUSION: Valoctocogene roxaparvovec provides durable hemostatic efficacy, FVIII activity, and improved health-related quality of life for ≥5 years, with no new safety signals.

Reimagining Nerve Injury Care Through Digital Twins: A Conceptual Framework, Ethan Blum, Christopher J Dy

2020-Current year OA Pubs

No abstract provided.

A Quantitative Cell-Based Reporter Links Tdp-43 Aggregation And Dysfunction To Define Pathogenic Mechanisms, Lohany Diax Mamede, Miwei Hu, Jaime Vaquer-Alicea, Amanda R. Titus, Patricia M. Passos, Erica Lantelme, Rachel L French, Paige A. Kirschner, Marc I. Diamond, Timothy M. Miller, Yuna M. Ayala

2020-Current year OA Pubs

TDP-43 pathology is a hallmark of fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and limbic-predominant age-related TDP-43-encephalopathy (LATE). In affected patients, cytoplasmic TDP-43 aggregates are accompanied by disruption of its normal nuclear localization and function. Because TDP-43 is an RNA binding protein that controls transcript processing, including repression of cryptic exon splicing, its loss leads to dysregulation of gene expression. Despite its central significance in disease, the connection between TDP-43 aggregation and dysfunction remains poorly understood, and models to study the underlying mechanisms are limited. Here, we characterize a robust and quantitative cell-based reporter that captures …

Predicting Onset Of Symptomatic Alzheimer's Disease With Plasma P-Tau217 Clocks, Kellen K Petersen, Yan Li, Chengjie Xiong, Benjamin Saef, Carlos Cruchaga, Eric Mcdade, David M Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler, Et Al.

2020-Current year OA Pubs

Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimer's disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible. Using longitudinal plasma %p-tau217 (the ratio of phosphorylated to non-phosphorylated tau at position 217) from two independent cohorts (n = 258 and n = 345), clock models were used to estimate the age at plasma %p-tau217 positivity. The estimated …

Comparing Ckd Populations With T1d And T2d: A Perspective Based On The Fine-One And Fidelity Populations, Hiddo J L Heerspink, Janet B Mcgill, Et Al.

2020-Current year OA Pubs

Chronic kidney disease (CKD) is a common comorbidity of both type 1 diabetes (T1D) and type 2 diabetes (T2D) and is associated with increased mortality, end-stage kidney disease and cardiovascular disease risk. Despite standard-of-care treatment with renin-angiotensin system inhibitors added to blood pressure and glycaemic control, people with CKD and T1D have a residual risk of CKD progression. Advances in therapeutic management have been limited over the past 3 decades, especially compared with CKD in T2D, for which new treatment options have emerged in the last 5 years. In this review article we discuss the similarities and differences between T1D …

What Constitutes Risk In Implementation Research? Perspectives From A Qualitative Key-Informant Study, Emmanuel K Tetteh, Gifty Aboagye-Mensah, Nwaliweaku Anidi, Elvin H Geng, Byron J Powell, Enola K Proctor, Mark D Huffman, Alison L Antes

2020-Current year OA Pubs

BACKGROUND: As implementation research increasingly occurs within routine care settings, determining what constitutes minimal risk is critical to ensuring that ethical oversight is appropriate and proportional. Current regulatory definitions often do not reflect the unique features of implementation studies, including implementation strategy-related risks and system-level effects. Yet, little empirical evidence exists on how researchers themselves interpret minimal risk in this context.

METHODS: We conducted semi-structured qualitative interviews with 11 key informants, including investigators with experience in domestic and global implementation research. Participants were recruited through purposive sampling. Interviews explored how participants interpret the concept of minimal risk, identify risk-related concerns, …

Recognizing Structural And Social Determinants Of Health In The Diagnosis And Care Of Dementia, Shana D Stites, Sharnita Midgett, Nisha Patel, Kimberly Halberstadter, Rosalie Schumann, Marissa L Streitz, Yidan Shi, John C Morris, Jason Flatt, Crystal M Glover, Dawn Mechanic-Hamilton

2020-Current year OA Pubs

Structural and social determinants of health are environmental conditions that affect individuals' health and functioning across the life course. These determinants are salient factors at the apex of individual psychology, community variables, and larger sociological factors, exerting prominent effects on individuals' wellbeing. The National Institute on Aging seeks to understand their influence on aging and Alzheimer's disease. We propose that the benefits of doing so may reach beyond knowledge of disease mechanisms - it may also improve clinical outcomes. We describe efforts introducing structural and social determinants of health data into the national network of Alzheimer's disease research centers. We …

Laser Interstitial Thermal Therapy And Adjuvant Pembrolizumab In Recurrent High-Grade Astrocytoma: A Phase 1/Randomized Phase 2b Trial, Jian L Campian, Omar H Butt, Yifei Xu, Jingxia Liu, William A Leidig, Tanner Johanns, George Ansstas, Alice Y Zhou, Sangami Pugazenthi, Jiayi Huang, Milan G Chheda, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response. A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582 ) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose. The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed …

Regional Brain Age Is Decreased In Children With Sickle Cell Anemia, Amy E Mirro, Landon C Power, Jinli Wang, Paula Germino-Watnick, Heather Roberts, Yonca Cam, Kristin P Guilliams, Slim Fellah, Yasheng Chen, Hongyu An, Jin-Moo Lee, Andria L Ford, Melanie E Fields

2020-Current year OA Pubs

DeepBrainNet, a machine learning tool, uses magnetic resonance imaging (MRI) to predict an individual's brain age, allowing calculation of the brain age gap (predicted chronological age) for use as a biomarker of brain health. We tested the DeepBrainNet tool in sickle cell anemia (SCA) on 210 brain MRIs from 130 children (90 with SCA; 40 healthy controls) to investigate the hypothesis that children with SCA would have a younger predicted brain age than healthy controls as an index of aberrant brain development. DeepBrainNet estimates brain age from 80 axial slices of each brain, with the median used as global brain …

Benefit Of Rituximab Maintenance After First-Line Bendamustine-Rituximab In Patients With Mantle Cell Lymphoma, Yucai Wang, Imran A Nizamuddin, Brad S Kahl, Et Al.

2020-Current year OA Pubs

The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient …

Ketogenic Diet Dampens Excitatory Neurotransmission By Shrinking Synaptic Vesicle Pools, Marion I Stunault, Pan-Yue Deng, Anjali Yadav, Erica M Periandri, Francisca N De Luna Vitorino, Michael B Thomsen, Jasmin Sponagel, Amelia J Barfield, Renzelle J Ponce, Layla Foroughi, Benjamin A Garcia, Gabor Egervari, Vitaly A Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Ketogenic diet (KD) is used for the treatment of drug-resistant childhood epilepsy and has been proposed to improve outcomes in neurodegenerative diseases. However, the mechanisms by which KD alters brain circuitry remain unclear. Here, we investigated the impact of KD on hippocampal function through integrative analysis of gene expression and neurotransmission. We found that KD induces extensive transcriptional reprogramming, including altered expression of numerous synaptic genes. Proteomic and genomic profiling revealed significant changes in histone modifications, particularly at promoters of KD-regulated genes. Electrophysiological recordings showed that KD reduces excitatory synaptic gain and short-term plasticity at CA3-CA1 synapses, dampening the summation …

Estimating The Baseline Age When Longitudinal Changes In Biomarkers Accelerate: Application To An Imaging Study Of Preclinical Alzheimer Disease, Chengjie Xiong, Folasade Agboola, Jingqin Luo

2020-Current year OA Pubs

BACKGROUND: Biomarkers are routinely measured from human biospecimens and imaging scans in Alzheimer disease (AD) research. Age is a well-known risk factor for AD. Detecting the baseline age at which the longitudinal change in biomarkers starts to accelerate is important to design preventive interventions. METHODS: We analyzed longitudinal biomarker data by a random intercept and random slope model where the slope (longitudinal rate of change) was modeled as a piecewise linear and continuous function of baseline age. We proposed to estimate the baseline age at the intersection of the two linear functions by multiple methods: maximum (profile) likelihood, minimum squared …

Applying Frame-Is To Characterize Provider-Led Adaptations To A Cervical Cancer Prevention Intervention In Kenya, Harriet Fridah Adhiambo, Katherine Thomas, Megan M Coe, Lynda Oluoch, Valary Ihaji, Mary Bernadette Kerubo, Alex Kinyua, Sarah Njoroge, Kenneth Ngure, Michelle Shin, Thomas A Odeny, Bryan Weiner, Nelly Mugo, Sarah Gimbel

2020-Current year OA Pubs

BACKGROUND: Implementation strategies that are contextually refined are essential for optimizing the delivery of evidence-based interventions (EBI) to prevent cervical cancer in low-resource settings. This paper reports the application of the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) to capture and disseminate strategy adaptations made to a single-visit, screen-and-treat approach with thermal ablation (SV-SAT + TA) strategy aimed at establishing sustainable cervical cancer prevention services in Kenya.

METHODS: A FRAME-IS-based tracking spreadsheet was developed to document bundled site-specific implementation strategy adaptations and across 10 facilities. Data was collected during technical assistants' (TAs) site visits, phone calls, …