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Iodine-Promoted Oxidative Cross-Coupling For The Synthesis Of (E)-2-(3-Oxo-3-Phenylprop-1-En-1-Yl)-3-Phenylquinazolin-4(3 H)-One Via C-H Activation: Development Of Synthetic Tlx Agonists, Lingaiah Maram, Puhan Zhao, Thomas Koelblen, Lamees Hegazy, Thomas P Burris, Bahaa Elgendy

2020-Current year OA Pubs

We report the development of an efficient iodine-promoted oxidative cross-coupling reaction for the synthesis of (

Three Positively Charged Binding Sites On The Eastern Equine Encephalitis Virus E2 Glycoprotein Coordinate Heparan Sulfate- And Protein Receptor-Dependent Infection, Maria D H Alcorn, Chengqun Sun, Theron C Gilliland Jr, Tetyana Lukash, Christine M Crasto, Saravanan Raju, Michael S Diamond, Scott C Weaver, William B Klimstra

2020-Current year OA Pubs

Naturally circulating strains of eastern equine encephalitis virus (EEEV) bind heparan sulfate (HS) receptors and this interaction has been linked to neurovirulence. Previous studies associated EEEV-HS interactions with three positively charged amino acid clusters on the E2 glycoprotein. One of these sites has recently been reported to be critical for binding EEEV to the very-low-density lipoprotein receptor (VLDLR), an EEEV receptor protein. The proteins apolipoprotein E receptor 2 (ApoER2) isoforms 1 and 2, and LDLR have also been shown to function as EEEV receptors. Herein, we investigate the individual contribution of each HS interaction site to EEEV HS- and protein …

A Rapid, Simple, And Economical Method For The Isolation Of Ribosomes And Translational Machinery For Structural And Functional Studies, Jessey Erath, Danielle Kemper, Elisha Mugo, Alex Jacoby, Elizabeth Valenzuela, Courtney F Jungers, Wandy L Beatty, Yaser Hashem, Marko Jovanovic, Sergej Djuranovic, Slavica Pavlovic Djuranovic

2020-Current year OA Pubs

Ribosomes are RNA-protein complexes essential for protein synthesis and quality control. Traditional methods for ribosome isolation are labor-intensive, expensive, and require a substantial amount of biological material. In contrast, our method, RNA affinity purification using poly-lysine (RAPPL), provides a rapid, simple, and cost-effective alternative applicable to various species and types of starting material (cell lysates, whole cells, organs, or whole organisms). It is also compatible with traditional isolation techniques. Here, we describe the use of RAPPL for rapid isolation, functional screening, and structural analysis of ribosomes and associated factors. We also demonstrate the application of RAPPL in investigating ribosome-associated resistance …

Provider's Attitudes Towards Telehealth And Parenting Interventions During Covid-19 Pandemic: An Exploratory Cross-Sectional Study From Brazil And Mexico, Marina Kohlsdorf, Cole Hooley, Alejandro L Vázquez, Mariana M Juras, Grant Decker, Taylor Iskalis, Kayla Miller, Quinn Tompkins, Nancy G A Buenabad, Michela Ribeiro, Acileide C F Coelho, Ana A Baumann

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic presented challenges for mental health providers all over the world, since they had to abruptly change from in person assistance to remote meetings. The adverse effects from social isolation were critical in Latinx populations such as Brazil and Mexico, since these countries faced a great amount of social, health, and economic burden during the pandemic, which affected families' access to care and increased inappropriate parenting practices.

OBJECTIVE: This study aimed to understand the impacts of adapting parenting interventions to online sessions for Brazilian and Mexican providers, due to the COVID-19 pandemic.

METHODS: Sixty-two Brazilian and 49 …

Alternative To The Statistical Mass Confusion Of Testing For "No Effect", Josh L Morgan

2020-Current year OA Pubs

In cell biology, statistical analysis means testing the hypothesis that there was no effect. This weak form of hypothesis testing neglects effect size, is universally misinterpreted, and is disastrously prone to error when combined with high-throughput cell biology. The solution is for analysis of measurements to start and end with an interpretation of effect size. In this manuscript, I walk through some of the common critiques of significance testing and how they relate to experimental cell biology. I argue that careful consideration of effect size should be returned to its central position in the planning and discussion of cell biological …

How Much Variance Exists Among Published Definitions Of Proximal Junctional Kyphosis? A Retrospective Cohort Study Of Adult Spinal Deformity, Tim T Bui, Karan Joseph, Alexander T Yahanda, Samuel Vogl, Miguel Ruiz-Cardozo, Camilo A Molina

2020-Current year OA Pubs

No abstract provided.

Detection Of Brain Cancer Using Genome-Wide Cell-Free Dna Fragmentomes, Dimitrios Mathios, Et Al.

2020-Current year OA Pubs

UNLABELLED: Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer diagnosis. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n = 148) or without (n = 357) brain cancer. Machine learning analyses of cfDNA fragmentome features detected brain cancer across all-grade gliomas (AUC = 0.90; 95% confidence interval, 0.87-0.93), and these results were validated in an independent prospectively collected cohort. cfDNA fragmentome changes in patients with gliomas represented …

An Ethanol-Induced Loss Of The Lipid Droplet-Associated Segregase Vcp/P97 Leads To Hepatic Steatosis, Sandhya Sen, Shaun Weller, Ryan J Schulze, Donglin Ding, Carol A Casey, Conrad Weihl, Mark A Mcniven

2020-Current year OA Pubs

The liver stores substantial numbers of neutral lipid organelles termed lipid droplets (LDs) that accumulate within hepatocytes in response to chronic ethanol (EtOH) consumption leading to hepatic steatosis. Mass spectrometry analysis of LDs isolated from EtOH-damaged rat livers revealed a substantial reduction in the valosin-containing protein ATPase (VCP/p97) that acts to remove targeted proteins from cellular membranes for degradation. Experimental disruption of VCP function resulted in an increase in LD content in hepatocytes and mouse livers along with a marked increase in LD-associated hydroxysteroid dehydrogenase (HSD17β13) known to contribute to hepatic steatosis. Surprisingly, treatment of hepatocytes with the proteasome inhibitor …

Long-Term Follow-Up Of Left Atrial Appendage Exclusion: Results Of The V-Clip Multi-Center Post-Market Study, Elias Zias, Katherine G Phillips, Marc Gerdisch, Scott Johnson, Ahmed El-Eshmawi, Kenneth Saum, Michael Moront, Michael Kasten, Chanderdeep Singh, Gautam Bhatia, Hiroo Takayama, Ralph Damiano

2020-Current year OA Pubs

No abstract provided.

Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function For Ocular Surface Repair, Emily Elizabeth Fresenko, Jian-Xing Ma, Matthew Giegengack, Atalie Carina Thompson, Anthony Atala, Andrew J W Huang, Yuanyuan Zhang

2020-Current year OA Pubs

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells …

Sporadic Als Induced Pluripotent Stem Cell Derived Neurons Reveal Hallmarks Of Tdp-43 Loss Of Function, Jeffrey D Rothstein, Olivia Keeley, Caroline Warlick, Timothy M Miller, Cindy V Ly, Jonathan D Glass, Alyssa N Coyne

2020-Current year OA Pubs

Nuclear loss and cytoplasmic buildup of the RNA-binding protein TDP-43 is a hallmark of ALS and related disorders. While studies using artificial TDP-43 depletion in neurons have revealed changes in gene expression and splicing, their relevance to actual patients remained unclear. Induced pluripotent stem cell (iPSC)-derived neurons (iPSNs) from 180 individuals, including controls, C9orf72 ALS/FTD, and sporadic ALS (sALS) patients were used to generate and analyze ~32,500 qRT-PCR data points across 20 genes which identified variable, time-dependent signatures of TDP-43 loss of function in individual lines. Notably, the same changes were also seen in postmortem brain tissue from the same …

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 …

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), …

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, …

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 …

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 …

Association Between Nt-Probnp Changes And Clinical Outcomes In Paediatric Patients With Heart Failure: Insights From Panorama-Hf And Paradigm-Hf, Robert Shaddy, Charles Canter, Et Al.

2020-Current year OA Pubs

AIMS: The PANORAMA-HF trial demonstrated significant N-terminal pro-B-type natriuretic peptide (NT-proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT-proBNP levels with clinical outcomes in PANORAMA-HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT-proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM-HF trial.

METHODS AND RESULTS: This post hoc analysis utilized data from Part 2 of the PANORAMA-HF trial. Associations between baseline NT-proBNP levels, changes post-baseline 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 …

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 …

Germline Genetic Variation Impacts Clonal Hematopoiesis Landscape And Progression To Malignancy, Jie Liu, Duc Tran, Brian J Wiley, Irenaeus C C Chan, Indraniel Das, Li Ding, Yin Cao, Matthew J Walter, Daniel C Link, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

With age, clonal expansions occur pervasively across normal tissues yet only in rare instances lead to cancer, despite being driven by well-established cancer drivers. Characterization of the factors that influence clonal progression is needed to inform interventional approaches. Germline genetic variation influences cancer risk and shapes tumor mutational profile, but its influence on the mutational landscape of normal tissues is not well known. Here we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 new CH-predisposition genes, most of which predispose to CH driven by specific mutational events. CH-predisposition genes contribute to …

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 …

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 …

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: …

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 …

Sex-Related Variability In The Perception Of Symptoms Associated With Common Otolaryngologic Complaints, Sabrina K Wagner, Jakob L Fischer, Alvaro Navarro, Lily Trinh, Waleed M Abuzeid, Ian M Humphreys, Nadeem A Akbar, Sharan Shah, Jivianne T Lee, Tara Wu, John S Schneider, Edward D Mccoul, Charles A Riley, Anthony M Tolisano

2020-Current year OA Pubs

OBJECTIVE: To assess the differences in the symptoms associated with common otolaryngology complaints between male and female patients.

METHODS: Between June 2020 and July 2023, a multi-institutional cross-sectional study was performed at six tertiary academic otolaryngology practices using semantics-based questionnaires to assess the symptoms patients associate with the complaints of sinus infection, reflux, congestion, and dizziness. Patients selected symptoms from lists of proposed terms to describe the various conditions. The primary outcome measure was sex-related differences in respondent symptom selection.

RESULTS: Four separate questionnaires were completed by a total of 1495 patients (46.0% male, 54.0% female). Female patients more often …

Barriers And Facilitators To Accessing Healthcare For People With Parkinson's Disease In Latin America: A Qualitative Study, Christine Jeyachandran, Catherine Spooner, Ana Margarita Rodriguez Salgado, Matthew Prina, Joel Rhee, Jorge Jesus Llibre-Guerra, Dani Kim, Juan J Llibre-Rodriguez, Mark F Harris

2020-Current year OA Pubs

AIMS: The aim of the study was to identify the barriers and facilitators to healthcare access for people with Parkinson's disease (PWP) in Spanish-speaking Latin American countries (LAC) in Central and South America, to understand their drivers and consider the implications for health systems in LAC.

METHODS: Four online semi-structured focus groups were conducted with 25 PWP who provide education and/or support to PWP. The study was designed and implemented by a person with lived experience of PD. Data were mapped to an existing model of access to healthcare that incorporates provider and consumer abilities.

FINDINGS: There were multiple provider …

Medicaid Accessibility For Ophthalmologists And Optometrists In Florida: A Pilot Study, Darby D Miller, Isabella V. Wagner, Michael W. Stewart, Abhimanyu S. Ahuja, Syril Dorairaj, Richard D. Ten Hulzen, Aaron Y. Lee

2020-Current year OA Pubs

OBJECTIVE AND METHODS: This study aimed to evaluate Medicaid accessibility for ophthalmologists and optometrists in Florida. A cross-sectional telephone survey was conducted between February and March 2018 using a geographically uniform sample of 22 ophthalmologists and 80 optometrists registered with Medicaid. Providers were asked whether they accepted new Medicaid patients (adult and/or pediatric) and for the earliest available appointment. Categorical variables were compared using Fisher's exact test, and time to next appointment was analyzed using the Wilcoxon rank-sum test (α = 0.05).

RESULTS: Across all age groups, a greater proportion of ophthalmologists (95.4%) accepted some form of Medicaid compared to …

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 …

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 …

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 …