tbuckley/cabot-search huggingface dataset:
Patient-Reported Outcomes (PROs) With Abrocitinib Treatment in Adolescent Patients With Moderate-to-Severe Atopic Dermatitis (AD): Results From the Phase 3 JADE TEEN Study
Authors: Amy McMichael, Michael Cork, Joyce Teng, Ricardo Rojo, Hernan Valdez, Fan Zhang, Daniela Myers, Gary Chan, Marco DiBonaventura
Journal: Journal of Allergy and Clinical Immunology (2021)
Safety and effectiveness of bronchial thermoplasty after 10 years in patients with persistent asthma (BT10+): a follow-up of three randomised controlled trials
Authors: Rekha Chaudhuri, Adalberto Rubin, Kaharu Sumino, Jose Roberto Lapa e Silva, Robert Niven, Salman Siddiqui, Karin Klooster, Charlene McEvoy, Pallav L Shah, Michael Simoff, Sumita Khatri, Richard Barbers, G Mark Grubb, Edmund A McMullen, Jennifer L Olson, Michel Laviolette
Journal: The Lancet Respiratory Medicine (2021)
DeepCAPE: A Deep Convolutional Neural Network for the Accurate Prediction of Enhancers
Authors: Shengquan Chen, Mingxin Gan, Hairong Lv, Rui Jiang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract The establishment of a landscape of enhancers across human cells is crucial to deciphering the mechanism of gene regulation, cell differentiation, and disease development. High-throughput experimental approaches, which contain successfully reported enhancers in typical cell lines, are still too costly and time-consuming to perform systematic identification of enhancers specific to different cell lines. Existing computational methods, capable of predicting regulatory elements purely relying on DNA sequences, lack the power of cell line-specific screening. Recent studies have suggested that chromatin accessibility of a DNA segment is closely related to its potential function in regulation, and thus may provide useful information in identifying regulatory elements. Motivated by the aforementioned understanding, we integrate DNA sequences and chromatin accessibility data to accurately predict enhancers in a cell line-specific manner. We proposed DeepCAPE, a deep convolutional neural network to predict enhancers via the integration of DNA sequences and DNase-seq data. Benefitting from the well-designed feature extraction mechanism and skip connection strategy, our model not only consistently outperforms existing methods in the imbalanced classification of cell line-specific enhancers against background sequences, but also has the ability to self-adapt to different sizes of datasets. Besides, with the adoption of auto-encoder, our model is capable of making cross-cell line predictions. We further visualize kernels of the first convolutional layer and show the match of identified sequence signatures and known motifs. We finally demonstrate the potential ability of our model to explain functional implications of putative disease-associated genetic variants and discriminate disease-related enhancers. The source code and detailed tutorial of DeepCAPE are freely available at https://github.com/ShengquanChen/DeepCAPE.
The Riddle of Determining Cardiac Resynchronization Therapy Response: A Physiologic Approach to Dyssynchrony Therapy⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Thomas H. Marwick, Randall C. Starling
Journal: Journal of the American College of Cardiology (2008)
Covid-19: Surge testing for the South Africa variant begins in England
Authors: Gareth Iacobucci
Journal: BMJ (2021)

What is being deployed?The government announced this week that it was rolling out additional surge testing and sequencing capacity to a small number of UK locations where community based infections of the covid-19 variant first identified in South Africa (known as 501Y.V2) were found that could not be linked back to international travel.To date, 11 cases of this kind have been identified.
Task shifting: a common-sense approach in children with asthma?
Authors: Warren Lenney
Journal: Thorax (2021)

Over the last 9 months, the COVID-19 pandemic has been all consuming for virtually every country of the world; destroying lives, overwhelming health services and perplexing governments alike. Other medical disorders have taken a ‘relative’ back seat resulting in research and resources being diverted to best manage the devastating pandemic.

Asthma is a good example being the most common disorder seen in children worldwide but with a recent profile lower than previously, despite its continuing and significant morbidity. The Lancet Commission1 has re-enforced our understanding that asthma is a spectrum of airway diseases often poorly diagnosed and frequently inadequately treated. In previous decades, it was believed to be a disease solely of temperate climate countries, but we now know its frequency and particularly its severity have been rapidly climbing in low-income and middle-income countries. In sub-Saharan Africa (sSA), urbanisation, poverty, air pollution and lack of resources have all been implicated as causative factors. In a systematic review, 10%–20% of all children in sSA were reported to have symptomatic or severe asthma.2 This in countries where there may be only 2 trained doctors per 100 000 population. …
Environmental enrichment implies GAT-1 as a potential therapeutic target for stroke recovery
Authors: Yuhui Lin, Mengcheng Yao, Haiyin Wu, Feng Wu, Shiying Cao, Huanyu Ni, Jian Dong, Di Yang, Yanyu Sun, Xiaolin Kou, Jun Li, Hui Xiao, Lei Chang, Jin Wu, Yan Liu, Chunxia Luo, Dongya Zhu
Journal: Theranostics (2021)

Rationale: Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation. Methods: We used multifaceted approaches combining electrophysiology, chemogenetics, optogenetics, and floxed mice in a mouse photothrombotic stroke model to reveal the key target of EE-mediated stroke recovery. Results: EE reduced tonic gamma-aminobutyric acid (GABA) inhibition and facilitated phasic GABA inhibition in the peri-infarct cortex, thereby promoting network excitability and stroke recovery. These beneficial effects depended on GAT-1, a GABA transporter regulating both tonic and phasic GABA signaling, as EE positively regulated GAT-1 expression, trafficking, and function. Furthermore, GAT-1 was necessary for EE-induced network plasticity, including structural neuroplasticity, input synaptic strengthening in the peri-infarct cortex, output synaptic strengthening in the corticospinal tract, and sprouting of uninjured corticospinal axons across the midline into the territory of denervated spinal cord, and functional recovery from stroke. Moreover, restoration of GAT-1 function in the peri-infarct cortex by its overexpression showed similar beneficial effects on stroke recovery as EE exposure. Conclusion: GAT-1 is a key molecular substrate of the effects of EE on network excitability and consequent stroke recovery and can serve as a novel therapeutic target for stroke treatment during the repair phase.
Polysaccharide mycophenolate-based nanoparticles for enhanced immunosuppression and treatment of immune-mediated inflammatory diseases
Authors: Yuce Li, Yuchen Lou, Yu Chen, Jing Yang, Danqi Li, Biling Jiang, Jiajia Lan, Jingjing Wen, Yangxue Fu, Yamin Zhang, Juan Tao, Jintao Zhu
Journal: Theranostics (2021)

Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity. Methods: Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). The efficacy of these NPs for mediating immunosuppression and treatment of IMIDs was evaluated in imiquimod-induced psoriasis-like skin inflammation in Balb/c mice, a representative IMID model. Results: The MPA@Dex-MPA NPs exhibited high MPA loading efficiency, low albumin binding rates, and sustained MPA release, resulting in improved pharmacokinetics in vivo. Compared to free MPA, MPA@Dex-MPA NPs induced more robust therapeutic effects on IMIDs. Mechanistic studies indicated that MPA@Dex-MPA NPs were primarily distributed in dendritic cells (DCs) and significantly suppressed the overactivated DCs in vivo and in vitro. Furthermore, the recovered DCs rehabilitated the IL-23/Th17 axis function and significantly ameliorated imiquimod-induced psoriasis-like skin inflammation. Importantly, MPA@Dex-MPA NPs showed favorable safety and biocompatibility in vivo. Conclusion: Our results indicated the polysaccharide mycophenolate-based NPs to be highly promising for IMID treatment.
Abstract 15092: Temporal Trend and Distribution of Advanced Atherosclerotic Plaque Morphology Among Patients With Acute Coronary Syndrome
Authors: Fahimehalsadat Shojaei, Yuyin Liu, Homa Najafi, Sogand Goudarzi, Sahar Memar Montazerin, Sadaf Sharfaei, Farbod Zahedi Tajrishi, Sara Mehrsefat, Adeel Jamil, Jolanta Marszalek, Jane Lee, Gerald Chi
Journal: Circulation (2019)

Introduction: Plaque rupture (PR) and plaque erosion (PE) are the most common morphologies of atherothrombosis in acute coronary syndrome (ACS) and have distinctive pathophysiology and prognosis. T...
When things go wrong: exploring possible mechanisms driving the progressive fibrosis phenotype in interstitial lung diseases
Authors: Moisés Selman, Annie Pardo
Journal: European Respiratory Journal (2021)

Interstitial lung diseases (ILDs) comprise a large and heterogeneous group of disorders of known and unknown aetiology characterised by diffuse damage of the lung parenchyma. In recent years it has become evident that patients with different types of ILD are at risk of developing progressive pulmonary fibrosis, known as progressive fibrosing ILD (PF-ILD). This is a phenotype that behaves similar to idiopathic pulmonary fibrosis, the archetypical example of progressive fibrosis. PF-ILD is not a distinct clinical entity but describes a group of ILDs with similar clinical behaviour. This phenotype may occur in diseases displaying distinct aetiologies and different biopathology during their initiation and development. Importantly, these entities may have the potential for improvement or stabilisation prior to entering the progressive fibrosing phase. The crucial questions are: 1) why does a subset of patients develop a progressive and irreversible fibrotic phenotype even with appropriate treatment? and 2) what are the possible pathogenic mechanisms driving progression? Here, we provide a framework highlighting putative mechanisms underlying progression, including genetic susceptibility, ageing, epigenetics, structural fibrotic distortion, aberrant composition and stiffness of the extracellular matrix, and the emergence of distinct pro-fibrotic cell subsets. Understanding the cellular and molecular mechanisms behind PF-ILD will provide the basis for identifying risk factors and appropriate therapeutic strategies.
Prednisolone Treatment Reduces Type 2 Inflammation In Skin Lesions Of Patients With Atopic Dermatitis
Authors: Emma Price, Christiane Whetstone, Dhuha Al-Sajee, Sai Sakktee Krisna, Karen Howie, Caroline Munoz, Paul O'Byrne, Hermenio Lima, Roma Sehmi, Gail Gauvreau
Journal: Journal of Allergy and Clinical Immunology (2021)
Disparities in SARS-CoV-2 Testing in Massachusetts During the COVID-19 Pandemic
Authors: Scott Dryden-Peterson, Gustavo E. Velásquez, Thomas J. Stopka, Sonya Davey, Shahin Lockman, Bisola O. Ojikutu
Journal: JAMA Network Open (2021)

This cohort study examines disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing during the coronavirus disease 2019 (COVID-19) pandemic in Massachusetts.
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for<i>GNAQ</i>-Driven Uveal Melanoma
Authors: Justine S. Paradis, Monica Acosta, Robert Saddawi-Konefka, Ayush Kishore, Simone Lubrano, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, J. Silvio Gutkind
Journal: Clinical Cancer Research (2021)

Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in
Phase 1 Randomized Placebo-Controlled Study in Healthy Adult Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate – A Potential Treatment for COVID-19
Authors: Ohad Bentur, Richard Hutt, Donna Brassil, Per Bäckman, Igor Gonda, Homer Boushey, B. Cahrous, Barry Coller, Robert MacArthur
Journal: Journal of Allergy and Clinical Immunology (2021)
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2021
Authors: Mark S. Freedman, Kevin Ault, Henry Bernstein
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

At its October 2020 meeting, the Advisory Committee on Immunization Practices (ACIP)* approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2021. After the Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine by the Food and Drug Administration, ACIP issued an interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years at its December 12, 2020, emergency meeting (1). In addition, ACIP approved an amendment to include COVID-19 vaccine recommendations in the child and adolescent and adult immunization schedules. After Emergency Use Authorization of Moderna COVID-19 vaccine by the Food and Drug Administration, ACIP issued an interim recommendation for use of Moderna COVID-19 vaccine in persons aged ≥18 years at its December 19, 2020, emergency meeting (2).
Quantification of Occupational and Community Risk Factors for SARS-CoV-2 Seropositivity Among Health Care Workers in a Large U.S. Health Care System
Authors: Julia M. Baker, Kristin N. Nelson, Elizabeth Overton, Benjamin A. Lopman, Timothy L. Lash, Mark Photakis, Jesse T. Jacob, John D. Roback, Scott K. Fridkin, James P. Steinberg
Journal: Annals of Internal Medicine (2021)

Identifying occupational risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs) can improve HCW and patient safety.To quantify demographic, occupational, and community risk factors for SARS-CoV-2 seropositivity among HCWs in a large health care system.A logistic regression model was fitted to data from a cross-sectional survey conducted in April to June 2020, linking risk factors for occupational and community exposure to coronavirus disease 2019 (COVID-19) with SARS-CoV-2 seropositivity.A large academic health care system in the Atlanta, Georgia, metropolitan area.Employees and medical staff members elected to participate in SARS-CoV-2 serology testing offered to all HCWs as part of a quality initiative and completed a survey on exposure to COVID-19 and use of personal protective equipment.Demographic risk factors for COVID-19, residential ZIP code incidence of COVID-19, occupational exposure to HCWs or patients who tested positive on polymerase chain reaction test, and use of personal protective equipment as potential risk factors for infection. The outcome was SARS-CoV-2 seropositivity.Adjusted SARS-CoV-2 seropositivity was estimated to be 3.8% (95% CI, 3.4% to 4.3%) (positive, n = 582) among the 10 275 HCWs (35% of the Emory Healthcare workforce) who participated in the survey. Community contact with a person known or suspected to have COVID-19 (adjusted odds ratio [aOR], 1.9 [CI, 1.4 to 2.6]; 77 positive persons [10.3%]) and community COVID-19 incidence (aOR, 1.5 [CI, 1.0 to 2.2]) increased the odds of infection. Black individuals were at high risk (aOR, 2.1 [CI, 1.7 to 2.6]; 238 positive persons [8.3%]).Participation rates were modest and key workplace exposures, including job and infection prevention practices, changed rapidly in the early phases of the pandemic.Demographic and community risk factors, including contact with a COVID-19-positive person and Black race, are more strongly associated with SARS-CoV-2 seropositivity among HCWs than is exposure in the workplace.Emory COVID-19 Response Collaborative.
Supplements for the Treatment of Mild COVID-19—Challenging Health Beliefs With Science From A to Z
Authors: Erin D. Michos, Miguel Cainzos-Achirica
Journal: JAMA Network Open (2021)

Suma Thomas, MD, MBA; Divyang Patel, MD, MS; Barbara Bittel, BSN, RN; Kathy Wolski, MPH; Qiuqing Wang, MS; Anirudh Kumar, MD, MS; Zachary J. Il'Giovine, MD; Reena Mehra, MD, MS; Carla McWilliams, MD; Steve E. Nissen, MD; Milind Y. Desai, MD, MBA
A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer
Authors: Arta M. Monjazeb, Anita Giobbie-Hurder, Ana Lako, Emily M. Thrash, Ryan C. Brennick, Katrina Z. Kao, Claire Manuszak, Ryan D. Gentzler, Anteneh Tesfaye, Salma K. Jabbour, Olatunji B. Alese, Osama E. Rahma, James M. Cleary, Elad Sharon, Harvey J. Mamon, May Cho, Howard Streicher, Helen X. Chen, Mansoor M. Ahmed, Adrian Mariño-Enríquez, Seunghee Kim-Schulze, Sacha Gnjatic, Emanual Maverakis, Alina I. Marusina, Alexander A. Merleev, Mariano Severgnini, Kathleen L. Pfaff, James Lindsay, Jason L. Weirather, Srinika Ranasinghe, Alexander Spektor, Scott J. Rodig, F. Stephen Hodi, Jonathan D. Schoenfeld
Journal: Clinical Cancer Research (2021)

Prospective human data are lacking regarding safety, efficacy, and immunologic impacts of different radiation doses administered with combined PD-L1/CTLA-4 blockade.
Improved Detection of Postoperative Residual Meningioma with [68Ga]Ga-DOTA-TOC PET Imaging Using a High-resolution Research Tomograph PET Scanner
Authors: Asma Bashir, Vibeke A. Larsen, Morten Ziebell, Kåre Fugleholm, Ian Law
Journal: Clinical Cancer Research (2021)

PET with somatostatin receptor ligand [68Ga]Ga-DOTA-D-Phe1-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue. We investigated the diagnostic accuracy of supplementary [68Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR).Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [68Ga]Ga-DOTA-TOC PET. Detection and volume measurements of [68Ga]Ga-DOTA-TOC-avid lesions in relation to the primary tumor site were recorded. Residual tumor in suspicious lesions suggested by [68Ga]Ga-DOTA-TOC PET was verified by (i) tumor recurrence/progression on subsequent MRI scans according to the Response Assessment of Neuro-Oncology criteria, (ii) subsequent histology, and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scan.Twenty-three PET scans demonstrated [68Ga]Ga-DOTA-TOC-avid lesions suspicious of residual meningioma, where 18 could be verified by (i) tumor progression on subsequent MRI scans (n = 6), (ii) histologic confirmation (n = 3), and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scans confirming the initial PET findings (n = 9) after an overall median follow-up time of 17 months (range, 9-35 months). In contrast, disease recurrence was seen in only 2 of 14 patients without [68Ga]Ga-DOTA-TOC-avid lesions (P < 0.0001). The sensitivity, specificity, and diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET in detecting meningioma residue was 90% [95% confidence interval (CI), 67-99], 92% (95% CI, 62-100), and 90% (95% CI, 74-98; P < 0.0001), respectively.The majority of patients with GTR on 3-month postoperative MRI may have small unrecognized meningioma residues that can be detected using [68Ga]Ga-DOTA-TOC PET.
p51/p63 induces secretory adhesion protein MFG-E8 in epithelial cells
Authors: Takeshi Okuyama, Yoshiya Tomimori, Rakuno Totsuka, Iyoko Katoh, Shizuko Kobayashi, Yoji Ikawa
Journal: Cancer Research (2005)

4537  p51/p63, a member of the tumor suppressor p53 family, is essential for skin, limb and craniofacial development, but less important for tumor suppressing function. A high level p51/p63 expression occurs in epidermal stem cells and several types of cancers including squamous cell carcinomas of head and neck, causing transactivation of its target genes: JAG1, REDD1 and ITGA3 as reported to date. The Milk Fat Globule-EGF factor 8 protein (MFG-E8) is a secretory adhesion molecule identified as breast antigen 46 (BA46) or Lactadherin in humans. Mouse MFG-E8 has been found to play critical roles in engulfment of apoptotic cells by macrophages and immature dendritic cells, and in sperm-egg binding for fertilization. MFG-E8 can serve as a linker between cell surface receptor integrin αvβ3/αvβ5 and phospholipid. We detected MFG-E8 expression in the basal and suprabasal cells in human skin tissues as well as in neonatal human keratinocyte cultures, indicating that MFG-E8 expression coincides with p51/p63 expression. Furthermore, both p51/p63 and MFG-E8 are known to be frequently overexpressed in breast cancers. Because p53 (p51/p63) binding consensus sequences existed in the enhancer/promoter region of the human MFGE8 gene, we examined whether p51/p63 has an activity to induce the expression of MFGE8. In the tetracycline-regulated p51/p63 expression system in HEK293 cells, the TA isoforms of p51/p63 enhanced endogenous MFGE8 expression as expected. After cloning an approximatly 2kb region upstream of the MFGE8 coding sequences, we performed a luciferase (luc) reporter assay in HeLa, HEK293 and Saos-2 cells. Activation of the luc gene expression by p53, p51A/TAp63γ and p51B/TAp63α was evident. However, ΔNp51A/ΔNp63γ known as a dominant-negative type isofoms was not found suppressive to the luc expression, and caused a level of the promoter activation in some cell lines. By deletion and mutation analyses, we identified the motifs at -370 and -27 as the target sequence for p51A/TAp63γ and ΔNp51A/ΔNp63γ, respectively. A chromatin immunoprecipitation (ChIP) assay with hemagglutinin (HA)-tagged p51A/TAp63γ supported the results. However, neither of the possible p53 binding sites was not responsive to p53, implying that p53 indirectly affects the MFGE8 enhancer/promoter region. These results suggest that p51/p63 participates in regulation of cell adhesion in the processes of development and tumorgenesis by inducing MFGE8 in epithelial basal cells. (This study was supported by grants-in-aid for Scientific Research on Priority Areas from MEXT Japan.)