Digital Commons Network^™

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. …

Aging Reduces Motivation Through Decreased Bdnf Expression In The Ventral Tegmental Area, Hanyue Cecilia Lei, Kyle E Parker, Chao-Cheng Kuo, Carla M Yuede, Jordan G Mccall, Shin-Ichiro Imai

2020-Current year OA Pubs

Age-associated reduced motivation is a hallmark of neuropsychiatric disorders in the elderly. In our rapidly aging societies, it is critical to keep motivation levels high enough to promote healthspan and lifespan. However, how motivation is reduced during aging remains unknown. Here, we used multiple mouse models to evaluate motivation and related affective states in young and old mice. We also compared the effect of social isolation, a common stressor in aged populations, to those of aging. We found that both social isolation and aging decreased motivation in mice, but that Bdnf expression in the ventral tegmental area (VTA) was selectively …

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 ± …

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

2020-Current year OA Pubs

No abstract provided.

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 …

Emerging Options And Future Strategies In Immunotherapy For Advanced Lung Squamous-Cell Carcinoma, Y Wang, R Rosell, F R Hirsch, S Lu, R Govindan, K Park, S Peters, J J Zhang

2020-Current year OA Pubs

Advanced-stage lung squamous-cell carcinoma (LUSC) remains a therapeutic challenge. Although immune checkpoint inhibitors (ICIs) have revolutionized LUSC treatment, only a small subset of LUSC patients can achieve durable clinical benefits, underscoring the need for novel strategies. Emerging immunotherapy strategies have demonstrated early evidence of promise for LUSC patients, particularly multi-specific antibodies and fusion proteins, antibody-drug conjugates, adoptive cell therapies, and cancer vaccines. Additionally, advances in multi-omics and artificial intelligence offer potential for precise immunotherapy by deciphering the complex tumor-immune microenvironment and predicting therapeutic responses. The future of LUSC treatment lies in rational multi-target and biological therapies to boost immune cytotoxicity, …

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 …

Finding Significant Hits In Networks: A Network-Based Tool For Analyzing Gene-Level P-Values To Identify Significant Genes Missed By Standard Methods, Sandeep Acharya, Vaha Akbary Moghaddam, Wooseok J Jung, Yu S Kang, Shu Liao, Michael A Province, Michael R Brent

2020-Current year OA Pubs

Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more …

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

Accuracy And Reliability Of Artery-Vein Differentiation In Small-Field Macular Oct Angiography, Haneen Alfauri, Tugce Ilayda Turer, Cyriac Manjaly, Aditya Santoki, Senyue Hao, Marin Woronets, Chao Zhou, Rithwick Rajagopal

2020-Current year OA Pubs

PURPOSE: Accurate artery-vein (AV) differentiation in small-field macular optical coherence tomography angiography (OCTA) remains challenging due to a lack of standardized guidelines. We propose and validate criteria for

APPROACH: Small field-of-view (FOV) OCTA scans were analyzed using established AV criteria for large-field (

RESULTS: A total of 465 vessels from 20 healthy eyes were evaluated across 3 pseudo-branching orders using the criteria for OCTA. Annotators achieved high accuracy (95.1%, 92.3%) and strong intra/inter-rater reliability (

CONCLUSIONS: Accurate and reproducible AV labeling is feasible in

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 …

Cdk4/6 Inhibition Mitigates Chemotherapy-Induced Expansion Of Tp53-Mutant Clonal Hematopoiesis, Irenaeus C C Chan, Giulia Petrone, J Scott Beeler, Duc Tran, Griffen Mustion, Catrina Fronick, Carlos Cruchaga, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Therapy-related myeloid neoplasm (tMN) is a fatal consequence of exposure to cytotoxic therapy administered in the treatment of cancer. Individuals with pre-existing TP53 clonal hematopoiesis (CH) are at high risk of tMN, with avoidance of therapy being the only strategy to reduce tMN risk. Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of …

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.

Signal Peptidase Complex Mediates Rotavirus Vp7 Processing And Virion Assembly, Xuejiao Zhu, Enkai Li, Liliana Sanchez-Tacuba, Wandy Beatty, Bin Li, Siyuan Ding

2020-Current year OA Pubs

For viruses that replicate in the proximity of or bud at the endoplasmic reticulum (ER) associated membranes, proper processing of their glycoproteins is critical for successful infection. Rotavirus outer capsid protein VP7 is an ER-resident protein. However, its N-terminal signal peptide is removed by an unknown proteolytic mechanism. In this study, we leveraged tandem affinity purification followed by high-resolution mass spectrometry to profile host proteins that interact with VP7. We identified members of the signal peptidase complex (SPC) family as important host factors that facilitate rotavirus infection. CRISPR knockout or siRNA knockdown of distinct SPC subunits resulted in significant decrease …

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 …

Intraocular Amyloidosis Presenting With Secondary Glaucoma: A Clinical-Pathologic Report And Literature Review, Joseph B Lin, James C Liu, Rajendra S Apte, George J Harocopos

2020-Current year OA Pubs

PURPOSE: We describe a case of intraocular amyloidosis presenting as secondary glaucoma, highlighting the clinical presentation and pathologic correlates. We also review the medical literature on all prior reported cases and discuss the diagnostic challenges pertinent to this particular case.

OBSERVATIONS: We report the case of a 72-year-old man presenting with medically intractable elevations of intraocular pressure. On clinical examination, the anterior segment was unremarkable, but there were significant vitreous opacities. The patient underwent tube shunt surgery, and a simultaneous aqueous humor biopsy was acellular and nondiagnostic. A subsequent pars plana vitrectomy demonstrated amyloid aggregates on histology. Mass spectrometric analysis …

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 …

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 …

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 …

Parkinson's Disease As A Somato-Cognitive Action Network Disorder, Jianxun Ren, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Parkinson's disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms

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 …

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 …

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 …

Active Bone Marrow Dose Reconstruction In A Large-Scale Cohort Study Of Cancer Patients Treated With Photon Radiotherapy, Keith T Griffin, Kishan J Pithadia, Yeon Soo Yeom, Lior Braunstein, Kelly L Bolton, Lindsay M Morton, Choonsik Lee

2020-Current year OA Pubs

BACKGROUND: Previous studies have investigated the dose-response relationship between external beam radiotherapy (EBRT) and leukemia by reconstructing the mean active bone marrow (ABM) dose as part of the exposure assessment. However, no prior study has leveraged electronic medical records (EMR) to reconstruct ABM dose and dose-volume in an EBRT patient population.

PURPOSE: To support future studies on the relationship between radiation exposure and adverse health effects among EBRT patients, we demonstrate methods to retrospectively calculate ABM dose and dose-volume metrics in a large patient cohort using EMR.

METHODS: We retrieved complete EMR for 639 individuals (five pediatric and 634 adult) …

Single Zonular Fiber Extraction And Characterization: A Platform For Biomechanical, Biochemical And Structural Analyses, Riley Forinash, Sean Staggs, Steven Bassnett, Juan Rodriguez

2020-Current year OA Pubs

Zonular fibers are essential for suspending the lens within the eye and, in primates, for transmitting forces generated by the ciliary body to drive ocular accommodation. Despite their biomechanical importance, the response of these fibers to sudden strains, and the molecular basis of their exceptional durability remain poorly understood. This is due, in part, to the absence of tools for studying them in isolation. Here, we present a custom-built, cost-effective apparatus designed to isolate, manipulate, and characterize individual zonular fibers under controlled physical and chemical conditions. The apparatus enables quantification of elastic moduli, stress-relaxation behavior, Poisson's ratio, and response to …

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 …