Digital Commons Network^™

High-Density Lipoprotein-Associated Cholesterol Abnormalities In A Clinical Outcomes Study Of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2, Zoe White, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limb-girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, DYSF. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.

METHODS: Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated …

Muscle Biopsy Findings In Valosin-Containing Protein Multisystem Proteinopathy, Marianela Schiava, Manouela V. Valtcheva, Conrad Weihl, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Valosin Containing Protein-associated multisystem proteinopathy (VCP-MSP) is a progressive, autosomal dominant disorder caused by pathogenic variants in the VCP gene, resulting in a heterogeneous clinical presentation. Muscle biopsy findings are characteristic but not pathognomonic. This study aimed to comprehensively analyse VCP-related myopathology and explore correlations with clinical phenotypes, genetic variants, and disease progression.

METHODS: Muscle biopsy images and data were collected retrospectively from adults (≥18 years) with pathogenic or likely pathogenic VCP variants enrolled in the VCP Multicentre International Study. Biopsy data were standardized using the "Common Data Elements for Muscle Biopsy Reporting." Variations in biopsy findings …

The Global Neurodegeneration Proteomics Consortium: Biomarker And Drug Target Discovery For Common Neurodegenerative Diseases And Aging, Farhad Imam, Muhammad Ali, Carlos Cruchaga, Chengran Yang, Et Al.

2020-Current year OA Pubs

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the …

Characteristics Of Responders To Interventions For Parkinson Disease: A Scoping Systematic Review, Sidney T. Baudendistel, Gammon M Earhart

2020-Current year OA Pubs

AIMS: The purpose of this review is to identify the characteristics of responders in interventions targeting motor function for individuals with Parkinson disease.

MATERIALS & METHODS: The primary search included, 'Parkinson' + 'responder.' A second, broader, search further included 'response' + 'responsiveness' + 'responsive.' Records were sorted by intervention: neuromodulation, pharmaceutical, physical, and placebo.

RESULTS: Thirteen studies were identified in the primary and 19 studies in the secondary search, culminating in 120 characteristics. For neuromodulation interventions, responders were younger at onset, more responsive to levodopa, and had more difficulties with activities of daily living. Responders to pharmaceuticals were younger at …

Echollm: Extracting Echocardiogram Entities With Light-Weight, Open-Source Large Language Models, Jonathan Chi, Yazan Rouphail, Ethan Hillis, Ningning Ma, An Nguyen, Jane Wang, Mackenzie Hofford, Aditi Gupta, Patrick G Lyons, Adam Wilcox, Albert M Lai, Philip R O Payne, Marin H Kollef, Caitlin Dreisbach, Andrew P Michelson

2020-Current year OA Pubs

OBJECTIVES: Large language models (LLMs) have demonstrated high levels of performance in clinical information extraction compared to rule-based systems and traditional machine-learning approaches, offering scalability, contextualization, and easier deployment. However, most studies rely on proprietary models with privacy concerns and high costs, limiting accessibility. We aim to evaluate 14 publicly available open-source LLMs for extracting clinically relevant findings from free-text echocardiogram reports and examine the feasibility of their implementation in information extraction workflows.

MATERIALS AND METHODS: We used 14 open-source LLM models to extract clinically relevant entities from echocardiogram reports (

RESULTS: In aggregate, Gemma2:9b-instruct had the highest precision, recall, …

Do Risk Factors For Hcc Impact The Association Of Ct/Mri Lirads Major Features With Hcc? An Individual Participant Data Meta-Analysis, Robert G Adamo, Daniel R Ludwig, Tyler J Fraum, Et Al.

2020-Current year OA Pubs

No abstract provided.

Combination Effect Of Finerenone And Empagliflozin In Participants With Chronic Kidney Disease And Type 2 Diabetes Using A Uacr Endpoint (Confidence) Trial: Baseline Clinical Characteristics, Rajiv Agarwal, Janet B Mcgill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) both reduce chronic kidney disease (CKD) progression and improve kidney/cardiovascular (CV) outcomes. The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint) study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, an SGLT2i, is superior to either drug alone in reducing urine albumin-to-creatinine ratio (UACR) over 6 months.

METHODS: CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R. Cox, Rabie Habib, Michael J. Bolt, Jessica B. Felix, Claudia E. Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M. Hartig

2020-Current year OA Pubs

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Integrative Genomic Reconstruction Reveals Heterogeneity In Carbohydrate Utilization Across Human Gut Bifidobacteria, Aleksandr A Arzamasov, Dmitry A Rodionov, Matthew C Hibberd, Janaki L Guruge, James E Kent, Marat D Kazanov, Semen A Leyn, Marinela L Elane, Kristija Sejane, Annalee Furst, Lars Bode, Michael J Barratt, Jeffrey I Gordon, Andrei L Osterman

2020-Current year OA Pubs

Bifidobacteria are beneficial saccharolytic microbes that are widely used as probiotics or in synbiotic formulations, yet individual responses to supplementation can vary with strain type, microbiota composition, diet and lifestyle, underscoring the need for strain-level insights into glycan metabolism. Here we reconstructed 68 pathways for the utilization of mono-, di-, oligo- and polysaccharides by analysing the distribution of 589 curated metabolic gene functions (catabolic enzymes, transporters and transcriptional regulators) across 3,083 non-redundant Bifidobacterium genomes of human origin. Thirty-eight predicted phenotypes were validated in vitro for 30 geographically diverse strains, supporting genomics-based predictions. Our analysis uncovered extensive inter- and intraspecies functional …

Human Thalamocortical Structural Connectivity Develops In Line With A Hierarchical Axis Of Cortical Plasticity, Valerie J Sydnor, Deanna M Barch, Et Al.

2020-Current year OA Pubs

Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in …

Autism And Intellectual Disability Due To A Novel Gain-Of-Function Mutation In Ube3a, Anna M Gunelson, Kwang-Soo Kim, Connolly G Steigerwald, Devorah Segal, Nicolas J Abreu, Jason J Yi

2020-Current year OA Pubs

The loss of maternal UBE3A causes Angelman syndrome whereas its duplication is associated with a heterogeneous neurodevelopmental disorder. Here, we describe two affected brothers who possess a novel UBE3A

Comparing Machine Learning Techniques For Neonatal Mortality Prediction: Insights From A Modeling Competition, Brynne A Sullivan, Alvaro G Moreira, Ryan M Mcadams, Lindsey A Knake, Ameena Husain, Jiaxing Qiu, Avinash Mudireddy, Abrar Majeedi, Wissam Shalish, Douglas E Lake, Zachary A Vesoulis

2020-Current year OA Pubs

BACKGROUND: Predicting mortality risk in neonatal intensive care units (NICUs) is challenging due to complex, variable clinical and physiological data. Machine learning (ML) offers potential for more accurate risk stratification.

OBJECTIVE: To compare the performance of various ML models in predicting NICU mortality using a team-based modeling competition.

METHODS: We conducted a modeling competition with five neonatologist-led teams applying ML techniques-logistic regression, CatBoost, neural networks, random forest, and XGBoost-to a shared dataset from over 6,000 NICU admissions. The dataset included static demographic and clinical variables, alongside daily samples of heart rate and oxygen saturation. Each team developed models to predict …

Impact Of Transcatheter Aortic Valve Replacement Use Ratio On Outcomes In Patients With Aortic Valve Disease, Theodore Marghitu, Sophia H Roberts, June He, Nicholas Kouchoukos, Puja Kachroo, Harold Roberts, Ralph Damiano, Alan Zajarias, Marc Sintek, John Lasala, Alexander A Brescia, Tsuyoshi Kaneko

2020-Current year OA Pubs

OBJECTIVE: Use of the Heart Team has been the standard of care for the treatment of aortic valve disease; however, its efficacy has not been evaluated. We sought to analyze its impact using the transcatheter aortic valve replacement (TAVR) use ratio (number of TAVR/total aortic valve replacement [AVR] volume) on TAVR, surgical aortic valve replacement (SAVR), and overall AVR outcomes.

METHODS: We analyzed all TAVRs and SAVRs sampled by the National Readmissions Database between 2016 and 2020. Hospitals were stratified into quartiles on the basis of their TAVR/AVR ratio. Centers with a ratio below the first quartile were considered "low …

Longer Scans Boost Prediction And Cut Costs In Brain-Wide Association Studies, Leon Qi Rong Ooi, Scott Marek, Nico U F Dosenbach, Timothy O Laumann, Evan M Gordon, Et Al.

2020-Current year OA Pubs

A pervasive dilemma in brain-wide association studies

The Ccjr® Charles A. Engh, Sr, Md. Excellence In Hip Research Award: Pelvic Tilt And Cup Position Change Significantly In Most Young Patients 10 Years After Hip Arthroplasty, Joseph J Kromka, William A Zuke, Caroline J Granger, John C Clohisy, Robert L Barrack

2020-Current year OA Pubs

BACKGROUND: Acetabular cup position is fundamental to total hip arthroplasty (THA) and surface replacement arthroplasty (SRA). Even if initial cup placement is adequate, changes in spinopelvic relationships alter functional acetabular position over time. This can lead to late complications. The purpose of this study was to examine changes in pelvic tilt and acetabular position in patients with at least 10 years of follow-up after THA or SRA.

METHODS: A retrospective review was conducted of patients from one academic practice who underwent THA or SRA and had at least 10 years of follow-up. Pelvic ratio was measured and converted to pelvic …

Autophagy Regulates Müller Glial Cell Inflammatory Activation, Teresa A Doggett, Zhenqing Zhou, Sohini Rebba, Jacqueline Unsinger, Philip A Ruzycki, Thomas A Ferguson

2020-Current year OA Pubs

PURPOSE: We tested whether Müller cells utilize autophagy to support immune privilege in the eye.

METHODS: The essential autophagy gene Atg5 was deleted in retinal Müller cells. Inflammation was induced by intravitreal injection of lipopolysaccharide (LPS) that was monitored by hematoxylin and eosin (H&E) staining, immunofluorescent confocal microscopy, and flow cytometry. Single-cell RNA sequencing was performed on retinal Müller cells isolated from control and Atg5-deficient mice. Markers of Müller cell gliosis were assessed, and cytokine production in the eye was measured. Small interfering RNA knockdown techniques were used to examine LPS-induced inflammatory pathways in culture.

RESULTS: We observed increased and …

Left Atrial And Ventricular Remodeling In Chronic Mitral Regurgitation, Jack J Yi, Martha Mcgilvray, Tari-Ann Yates, Samantha Procasky, Jakraphan Yu, Caleb Berberet, Nicholas Banull, Jie Zheng, Jonathan K Zoller, Matthew R Schill, Christian Zemlin, Ralph J Damiano Jr

2020-Current year OA Pubs

OBJECTIVE: This study describes the structural and mechanical changes in the left atrium and left ventricle in a canine model of chronic mitral regurgitation in an attempt to identify markers linked to the onset of atrial tachyarrhythmias or left ventricle dysfunction.

METHODS: Animals underwent baseline and terminal echocardiography and cardiac magnetic resonance imaging. Under echocardiographic guidance, chordae tendinae were avulsed until there was severe mitral regurgitation, defined by regurgitant jet area to left atrium area more than 70%. At terminal surgery, rapid atrial pacing was performed to test inducibility of atrial tachyarrhythmias.

RESULTS: Twelve canines underwent mitral valve chordae avulsion …

A Measurement Science Framework To Optimize Cds For Opioid Use Disorder Treatment In The Ed, Mark S. Iscoe, Carolina Diniz Hooper, Deborah R. Levy, John Lutz, Hyung Paek, Christian Rose, Thomas Kannampallil, Daniella Meeker, James D. Dziura, Edward R. Melnick

2020-Current year OA Pubs

In the emergency department-initiated buprenorphine for opioid use disorder (EMBED) trial, a clinical decision support (CDS) tool had no effect on rates of buprenorphine initiation in emergency department (ED) patients with opioid use disorder. The Agency for Healthcare Research and Quality (AHRQ) recently released a CDS Performance Measure Inventory to guide data-driven CDS development and evaluation. Through partner co-design, we tailored AHRQ inventory measures to evaluate EMBED CDS performance and drive improvements.Relevant AHRQ inventory measures were selected and adapted using a partner co-design approach grounded in consensus methodology, with three iterative, multidisciplinary partner working group sessions involving stakeholders from various …

Benefit Of Early Oseltamivir Therapy For Adults Hospitalized With Influenza A: An Observational Study, Nathaniel M Lewis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza.

METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during 1 October 2022-21 July 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), …

The Importance Of Imperfect Pre-Clinical Models In Adolescent Idiopathic Scoliosis, Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, …

Building Capacity And Equity In Implementation Science: Evaluation Of A National Mentored Training Program, Ross C Brownson, Shelly J Kannuthurai, Rebekah R Jacob, Leopoldo J Cabassa, Lisa M Klesges, Rachel G Tabak, Debra Haire-Joshu, Et Al.

2020-Current year OA Pubs

BACKGROUND: As implementation science evolves, it is essential to expand training capacity to build intellectual capital continually. The demand for training in implementation science far outstrips the current supply. This paper presents the methods and findings from the Institute for Implementation Science Scholars (IS-2) national training program (2020-2024).

METHODS: The IS-2 was a US-based, two-year training program that provided mentored training for early- and mid-career researchers interested in applying implementation science principles to reduce the burden of chronic disease disparities. Scholars attended two annual, 2.5-day intensive training sessions, received ongoing remote and in-person mentoring, and were supported by other activities …

Impact Of Hereditary Angioedema Attacks On Health-Related Quality Of Life And Work Productivity, Maeve O'Connor, Paula J Busse, Timothy J Craig, Cristine Radojicic, H James Wedner, Sherry Danese, Julie Ulloa, Vibha Desai, Tomas Andriotti, Paul K Audhya, Sandra Christiansen

2020-Current year OA Pubs

BACKGROUND: Hereditary angioedema (HAE) negatively impacts health-related quality of life (HRQoL). Few studies have characterized impairments to HRQoL, work productivity, and well-being during and following HAE attacks.

METHODS: Patients with ≥1 HAE attack in the previous 3 months were recruited by the United States (US) HAE Association (HAEA) to complete an online survey. Respondents were categorized into those who did (Treated Cohort) and did not (Untreated Cohort) manage their last attack with on-demand treatment (OD). Adapted versions of the EuroQol-Five Dimensions-Five Levels (EQ-5D-5L), EuroQol Visual Analogue Scale (EQ VAS), and Work Productivity and Activity Impairment-General Health assessments were used.

RESULTS: …

Inter-Organ Communication Is A Critical Machinery To Regulate Metabolism And Aging, Kyohei Tokizane, Shin-Ichiro Imai

2020-Current year OA Pubs

Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologies, implicating these processes as a potential target for therapeutic intervention to promote healthy aging. In this review, we delve into IOC mediated by hormonal signaling, circulating factors, organelle signaling, and neuronal networks and examine their roles in regulating metabolism and aging. Given the role of the hypothalamus as a high-order control center for aging and longevity, we particularly emphasize the importance of its communication with peripheral organs and pave the way …

Active Dna Demethylation Upstream Of Rod-Photoreceptor Fate Determination Is Required For Retinal Development, Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G. Harding, Shiming Chen, Meelad M. Dawlaty, Philip A. Ruzycki, John R. Edwards, Brian S. Clark

2020-Current year OA Pubs

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, …

Implementation Outcomes Of A Patient Decision-Aid In A Diverse Population With Systemic Lupus Erythematosus In 15 Us Rheumatology Clinics, Jasvinder A Singh, Seth Eisen, Alfred Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus.

METHODS: We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical …

Sex-Related Measurement Bias In Autism Spectrum Disorder Symptoms In The Baby Siblings Research Consortium, Catherine A Burrows, Natasha Marrus, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Disparities exist in age of diagnosis and prevalence of autism spectrum disorder (ASD) for female compared with male children. Correcting for sources of bias is critical for improving equitable ASD identification.

OBJECTIVE: To determine whether sex differences exist in measurement of ASD symptoms using the Autism Diagnostic Observation Schedule (ADOS) among young children at high familial likelihood (HFL) and low familial likelihood (LFL) of ASD.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study collected longitudinal, prospective data from the Baby Siblings Research Consortium between January 1, 2003, and December 31, 2021. Participants included 3106 children who had an older sibling …

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Screening Programmes And Breast Cancer Mortality: An Observational Study Of 194 Countries, Syed Mahfuz Al Hasan, Debbie L Bennett, Adetunji T Toriola

2020-Current year OA Pubs

OBJECTIVE: To investigate the associations between national breast cancer screening programmes and breast cancer mortality globally.

METHODS: We collected data on breast cancer screening programmes and breast cancer mortality from the World Health Organization's Global Health Observatory, the Global Burden of Diseases 2021 study and the Eurostat database. We assessed differences in breast cancer mortality between countries with regular and irregular screening programmes, adjusting for sociodemographic index. We calculated annual changes in breast cancer mortality from 2015 to 2021 and assessed differences in mortality changes between countries with regular and irregular screening programmes.

FINDINGS: Between 2015 and 2021, 94 of …

Massively Parallel Immunopeptidome By Dna Sequencing Provides Insights Into Cancer Antigen Presentation, Quanming Shi, Cheryl F Lichti, Et Al.

2020-Current year OA Pubs

Human leukocyte antigens (HLAs) are encoded by the most polymorphic genes in the human genome. HLA class I alleles control antigen presentation for T cell recognition, which is pivotal for autoimmunity, infectious diseases and cancer. Current knowledge of HLA-bound peptides is limited, skewed and falls short of population-wide HLA binding profiles for high-value targets. Here we present ESCAPE-seq (enhanced single-chain antigen presentation sequencing), a massively parallel platform for comprehensive screening of class I HLA-peptide combinations for antigen presentation via deep DNA sequencing. ESCAPE-seq demonstrates programmability, high throughput, sensitivity and nominated viral and cancer epitopes. We simultaneously assessed over 75,000 peptide-HLA …