tbuckley/cabot-search huggingface dataset:
A Porcine Model of Transvertebral Ultrasound and Microbubble-Mediated Blood-Spinal Cord Barrier Opening
Authors: Stecia-Marie P. Fletcher, Min Choi, Natalia Ogrodnik, Meaghan A. O'Reilly
Journal: Theranostics (2020)

Blood-spinal cord barrier opening, using focused ultrasound and microbubbles, has the potential to improve drug delivery for the treatment of spinal cord pathologies.Delivering and detecting ultrasound through the spine is a challenge for clinical translation.We have previously developed short burst, phase keying exposures, which can be used in a dual-aperture configuration to address clinical scale targeting challenges.Here we demonstrate the use of these pulses for blood-spinal cord barrier opening, in vivo in pigs. Methods:The spinal cords of Yorkshire pigs (n=8) were targeted through the vertebral laminae, in the lower thoracic to upper lumbar region using focused ultrasound (486 kHz) and microbubbles.Four animals were treated with a combination of pulsed sinusoidal exposures (1.0-4.0MPa, non-derated) and pulsed short burst, phase keying exposures (1.0-2.0MPa, non-derated).Four animals were treated using ramped short burst, phase keying exposures (1.8-2.1 MPa, non-derated).A 250 kHz narrowband receiver was used to detect acoustic emissions from microbubbles.Blood-spinal cord barrier opening was assessed by the extravasation of Evans blue dye.Histological analysis of the spinal cords was used to assess tissue damage and excised vertebral samples were used in benchtop experiments.Results: Ramped short burst, phase keying exposures successfully modified the blood-spinal cord barrier at 16/24 targeted locations, as assessed by the extravasation of Evans blue dye.At 4 of these locations, opening was confirmed with minimal adverse effects observed through histology.Transmission measurements through excised vertebrae indicated a mean transmission of (47.0 ± 7.0 %) to the target.Conclusions: This study presents the first evidence of focused ultrasound-induced blood-spinal cord barrier opening in a large animal model, through the intact spine.This represents an important step towards clinical translation.
Expression of CTX-M-15 limits the efficacy of ceftolozane/tazobactam against Escherichia coli in a high-inoculum murine peritonitis model
Authors: J. Canovas, G. Petitjean, F. Chau, A. Le Monnier, B. Fantin, A. Lefort
Journal: Clinical Microbiology and Infection (2020)
VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release
Authors: Vivien Zell, Thomas Steinkellner, Nick G. Hollon, Shelley M. Warlow, Elizabeth Souter, Lauren Faget, Avery C. Hunker, Xin Jin, Larry S. Zweifel, Thomas S. Hnasko
Journal: Neuron (2020)
Acute lymphoblastic leukemia and down syndrome: 6-mercaptopurine and methotrexate metabolites during maintenance therapy
Authors: Anna Østergaard, Cathrine Bohnstedt, Kathrine Grell, Matilda Degn, Bernward Zeller, Mervi Taskinen, Solveig Hafsteinsdottir, Helga Björgvinsdóttir, Mats Heyman, Peter Hoogerbrugge, Kjeld Schmiegelow
Journal: Leukemia (2020)
EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multicentre study
Authors: Robert A. Lewis, Iain Armstrong, Carmel Bergbaum, Melanie J. Brewis, John Cannon, Athanasios Charalampopoulos, A. Colin Church, J. Gerry Coghlan, Rachel J. Davies, Konstantinos Dimopoulos, Charlie Elliot, J. Simon R. Gibbs, Wendy Gin-Sing, Gulam Haji, Abdul G. Hameed, Luke S. Howard, Martin K. Johnson, Aleksander Kempny, David G. Kiely, Francesco Lo Giudice, Colm McCabe, Andrew J. Peacock, Oyinkansola Peleyeju, Joanna Pepke-Zaba, Gary Polwarth, Laura Price, Ian Sabroe, Benjamin E. Schreiber, Karen Sheares, Dolores Taboada, A.A. Roger Thompson, Mark R. Toshner, Ivy Wanjiku, S. John Wort, Janelle Yorke, Robin Condliffe
Journal: European Respiratory Journal (2020)

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure.1745 patients with idiopathic PAH (IPAH), drug-induced PAH (DPAH), heritable PAH (HPAH) (collectively "(I/D/H)PAH"), or connective tissue disease-associated PAH (CTD-PAH), who had completed emPHasis-10 questionnaires at one of six UK referral centres between 2014 and 2017, were identified. Correlations with exercise capacity and World Health Organization (WHO) functional class were assessed, and exploratory risk stratification thresholds were tested.Moderate correlations were seen between emPHasis-10 scores and 6-min walk distance (r=-0.546), incremental shuttle walk distance (r=-0.504) and WHO functional class (r=0.497) (all p<0.0001). Distribution of emPHasis-10 score differed significantly between each WHO functional class (all p<0.0001). On multivariate analysis, emPHasis-10 score, but not WHO functional class, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with 1-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO functional class III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 scores had improved exercise capacity (p<0.0001) and patients who transitioned between risk groups demonstrated similar survival to patients originally in those risk groups.The emPHasis-10 score is an independent prognostic marker in patients with (I/D/H)PAH or CTD-PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.
FRI0571 THE DIAGNOSTIC VALUE OF KL-6 IN RHEUMATOID ARTHRITIS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE IN XINJIANG OF CHINA
Authors: G. Chen, L. Wu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease.Many researchers have observed that extra articular organs were highly involved in RA patients.The most common extra-articular manifestations were pulmonary involvement.Serum levels of KL-6 have been reported to be elevated in various ILD such as idiopathic pulmonary fibrosis, collagen vascular disease associated interstitial pneumonias, and other interstitial lung disorders.However, little is known regarding the usefulness of this biomarker in connective tissue diseases related interstitial lung diseases(CTD-ILD). Especially,the diagnostic value of KL-6 in interstitial lung disease associated with rheumatoid arthritis(RA-ILD) still has a dispute. Objectives: To assess the diagnosis of the serum Krebs von den Lungen-6(KL-6) for RA-ILD patients in Xinjiang of China. Methods: This retrospective study included 184 patients with RA in who visited the department of rheumatology and immunology of People’s Hospital of Xinjiang Uygur Autonomous Region between January, 2015 and December, 2019.The patients were divided into RA-ILD group(n=95) and RA group(n=89) according to the presence of ILD. Serum KL-6 concentration (U/mL) was measured using the chemiluminescent enzyme immunoassay kit. Results: The mean age(p &lt; 0.001) and median value of CCP (p = 0.006) were significantly higher in the RA-ILD group.RA-ILD group had elevated serum KL-6 levels compared to RA group [447(281, 687)U/ml vs 195(151.5,265.5)U/ml](p &lt; 0.001)(figure 1).According to the Receiver Operating Characteristic Curve (ROC) analysis, the area under the curve was of 0.879 and the optimal cut-off value of serum KL-6 to discriminate the presence of ILD was 277 U/ml, with sensitivity of 77.9%, specificity of 79.8%(figure 2). Figure 1. Comparison of serum KL-6 concentrations in RA-ILD group and RA group. Figure 2. Receiver-operating characteristic curve(ROC) of KL-6 for the diagnosis of RA-ILD Conclusion: The present study confirms that KL-6 is a biological marker which is associated with RA-ILD. Furthermore, Patients with RA who are older and have a higher value of CCP are more likely to develop ILD. References: [1] Anaya JM, Diethelm L, Ortiz LA et al (1995) Pulmonary involvement in rheumatoid arthritis. Semin Arthritis Rheum 24:242–254 [2] Bonella F, Costabel U (2014) Biomarkers in connective tissue disease-associated interstitial lung disease. Semin Respir Crit Care Med 35:181–200 [3] Doishita S, Inokuma S, Asashima H et al (2011) Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases. Intern Med 50: 2889–2892 Disclosure of Interests: None declared
Mapping regulatory variants controlling gene expression in drought response and tolerance in maize
Authors: Shengxue Liu, Cuiping Li, Hongwei Wang, Shuhui Wang, Shiping Yang, Xiaohu Liu, Jianbing Yan, Bailin Li, Mary Beatty, Gina Zastrow-Hayes, Shuhui Song, Feng Qin
Journal: Genome biology (2020)

Abstract Background Gene expression is a key determinant of cellular response. Natural variation in gene expression bridges genetic variation to phenotypic alteration. Identification of the regulatory variants controlling the gene expression in response to drought, a major environmental threat of crop production worldwide, is of great value for drought-tolerant gene identification. Results A total of 627 RNA-seq analyses are performed for 224 maize accessions which represent a wide genetic diversity under three water regimes; 73,573 eQTLs are detected for about 30,000 expressing genes with high-density genome-wide single nucleotide polymorphisms, reflecting a comprehensive and dynamic genetic architecture of gene expression in response to drought. The regulatory variants controlling the gene expression constitutively or drought-dynamically are unraveled. Focusing on dynamic regulatory variants resolved to genes encoding transcription factors, a drought-responsive network reflecting a hierarchy of transcription factors and their target genes is built. Moreover, 97 genes are prioritized to associate with drought tolerance due to their expression variations through the Mendelian randomization analysis. One of the candidate genes, Abscisic acid 8′-hydroxylase , is verified to play a negative role in plant drought tolerance. Conclusions This study unravels the effects of genetic variants on gene expression dynamics in drought response which allows us to better understand the role of distal and proximal genetic effects on gene expression and phenotypic plasticity. The prioritized drought-associated genes may serve as direct targets for functional investigation or allelic mining.
Transcriptional and Functional Analysis of CD1c+ Human Dendritic Cells Identifies a CD163+ Subset Priming CD8+CD103+ T Cells
Authors: Pierre Bourdely, Giorgio Anselmi, Kristine Vaivode, Rodrigo Nalio Ramos, Yoann Missolo-Koussou, Sofia Hidalgo, Jimena Tosselo, Nicolas Nuñez, Wilfrid Richer, Anne Vincent-Salomon, Alka Saxena, Kristie Wood, Alvaro Lladser, Eliane Piaggio, Julie Helft, Pierre Guermonprez
Journal: Immunity (2020)

Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88−CD1c+CD163+ DCs (called DC3s) as immediate precursors of inflammatory CD88−CD14+CD1c+CD163+FcεRI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8+ T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.
Investing in surgery: a value proposition for African leaders
Authors: Desmond T Jumbam, Ché L Reddy, Emmanuel Makasa, Adeline A Boatin, Khama Rogo, Kathryn M Chu, Benetus Nangombe, Olufemi T Oladapo, John G Meara, Salome Maswime
Journal: The Lancet (2020)
Response to: ‘COVID-19 in paediatric rheumatology patients treated with b/tsDMARDs: a cross-sectional patient survey study’ by Cuceoglu <i>et al</i>
Authors: Carlo Salvarani, Gianluigi Bajocchi, Pamela Mancuso, Elena Galli, Francesco Muratore, Paolo Giorgi Rossi
Journal: Annals of the Rheumatic Diseases (2020)

We appreciated the comment from Cuceoglu et al 1 in response to our paper on the susceptibility and severity of COVID-19 in a population-based cohort of patients treated with biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).2 We did not observe patients with COVID-19 <45 years in our cohort of 1195 cases with autoimmune diseases treated with b/tsDMARDs in Reggio Emilia area. Confirming our results, the authors did not observe cases of COVID-19 in a series of 173 Turkish paediatric patients with rheumatological conditions …
Abstract A54: Targeting new links in the proteostasis network as novel therapies in high-grade serous ovarian cancer
Authors: Kinzie Lighty, Yonghyun Shin, Fahmi Mesmer, Harikrishna Nakshatri, Marcin Iwanicki, Sumegha Mitra
Journal: Clinical Cancer Research (2020)

Abstract High-grade serous ovarian cancer (HGSOC) is the most lethal subtype of ovarian cancer with high case-to-fatality ratio. However, not much advancement has been seen in the field in terms of novel adjuvant therapies. Somatic or germline mutations in HGSOC along with copy number variations results in intratumoral genetic heterogeneity, which leads to tumor growth and development of chemoresistant clones and treatment resistance. Moreover, molecular heterogeneity also leads to the accumulation of aberrant peptides and protein complexes with altered stoichiometry, causing extensive proteotoxic stress in cancer cells and adding to the known misfolded proteins stress in cancer cells due to enhanced protein synthesis, thus making these cancer cells more dependent on the protein clearance mechanisms. Not much is known about the molecular targets from the proteostasis network and their therapeutic potential in HGSOC. Here we explore the regulation and role of different components of ubiquitin proteasome system (UPS) in HGSOC and investigate the therapeutic effect of small-molecule inhibitors of UPS. We identified overexpression of deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in HGSOC, and high UCHL1 levels were correlated with the disease stage, tumor grade, and poor clinical outcome. UCHL1 overexpression in HGSOC was driven by mutant p53-mediated H3K4 trimethylation at the UCHL1 regulatory region. Mutant p53-UCHL1 axis transcriptionally promoted the expression of proteasomal subunit alpha 7 (PSMA7) and acylaminoacyl-peptide hydrolase (APEH), resulting in increased proteasome activity in HGSOC. Silencing UCHL1 or inhibiting proteasome activity in vitro and in vivo remarkably reduced HGSOC growth. Together, these results highlight the novel mechanisms of regulation of proteostasis in HGSOC and potential therapies targeting regulators of proteasome pathway. Citation Format: Kinzie Lighty, Yonghyun Shin, Fahmi Mesmer, Harikrishna Nakshatri, Marcin Iwanicki, Sumegha Mitra. Targeting new links in the proteostasis network as novel therapies in high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A54.
LDtrait: An Online Tool for Identifying Published Phenotype Associations in Linkage Disequilibrium
Authors: Shu-Hong Lin, Derek W. Brown, Mitchell J. Machiela
Journal: Cancer Research (2020)

Abstract Genome-wide association studies (GWAS) have identified thousands of germline susceptibility loci associated with risk for cancer as well as a wide range of other traits and diseases. An interest of many investigators is identifying traits or diseases that share common susceptibility loci. We developed LDtrait (https://ldlink.nci.nih.gov/?tab=ldtrait) as an open access web tool for finding germline variation associated with multiple traits. LDtrait searches the NHGRI-EBI GWAS Catalog to identify susceptibility loci in linkage disequilibrium (LD) with a user-provided list of query variants. Options allow for modifying LD thresholds, calculating LD from a diverse set of reference populations, and downloading annotated variant lists. Results from example query searches highlight the utility of LDtrait in uncovering cross-trait associations for cancer risk and other traits. LDtrait accelerates etiologic understanding of cancer genetics by rapidly identifying genetic similarities with other traits or diseases. Significance: The new GWAS search tool LDtrait will expedite discovery of shared genetic components underlying seemingly unrelated diseases and may offer novel insights into cancer research.
Perspectives on Urinary Tract Infection and Race
Authors: Andrea T. Cruz, Angela M. Ellison, Tiffani J. Johnson
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia
Authors: Maciej Banach, P. Barton Duell, Antonio M. Gotto, Ulrich Laufs, Lawrence A. Leiter, G. B. John Mancini, Kausik K. Ray, JoAnn Flaim, Zhan Ye, Alberico L. Catapano
Journal: JAMA Cardiology (2020)

Additional lipid-lowering therapy options are needed for patients who cannot achieve sufficient decreases in low-density lipoprotein cholesterol (LDL-C) levels using statins alone or for those who are statin intolerant.
Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial
Authors: Christopher R Sudfeld, Ferdinand Mugusi, Alfa Muhihi, Said Aboud, Tumaini J Nagu, Nzovu Ulenga, Biling Hong, Molin Wang, Wafaie W Fawzi
Journal: The Lancet HIV (2020)
Cling film for mobile phones to prevent cross-infection during the COVID-19 pandemic
Authors: Mitanjali Sethy, Vamshi Krishna, Chakravarthi R. Srinivas
Journal: Journal of the American Academy of Dermatology (2020)

Mobile phones have become an inseparable part of dermatology practice, and dermatologists use mobile phones in various ways while clinically examining patients. They are often used as a flashlight or a camera to take images of the lesions. In the COVID-19 pandemic era, mobile phones are more likely to be contaminated with the virus in health care settings, and they must be sanitized properly after use because they can be possible carriers of the virus.1Van Doremalen N. Bushmaker T. Morris D.H. et al.Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1.N Engl J Med. 2020; 382: 1564-1567Crossref PubMed Scopus (6785) Google Scholar However, it is not practically feasible to sanitize mobile phones with alcohol-containing sanitizer or chlorine solutions because these chemical solutions may have ill effects on mobile phone screens. Cling film roll can be a better solution for this challenge. These are thin, transparent plastic wraps with smooth surfaces, that can be used to wrap a mobile phone thoroughly before reaching the hospital (Fig 1). Because it is transparent, the plastic wrap gives a clear view of the mobile screen. We did not find a significant rise in temperature of the mobile phone or a marked change in the resolution of images taken with the mobile camera after applying the cling film (Fig 2). After use, the phone wrapped with cling film can be sanitized with alcohol-based sanitizer because it is waterproof. In the end, the film can be removed completely from the phone and discarded.Fig 2Temperature of a mobile phone wrapped with cling film (A) before and (B) after 6 hours of use. Resolution of an image taken with a mobile phone (C) without cling film and (D) with cling film.View Large Image Figure ViewerDownload Hi-res image Download (PPT) At a time when there is intense focus on ways to prevent the spread of the disease, cling film is a plausible and cost-effective method for preventing cross-infection of severe acute respiratory syndrome coronavirus 2. Comment on "Cling film for mobile phones to prevent cross-infection during the COVID-19 pandemic"Journal of the American Academy of DermatologyVol. 84Issue 1PreviewTo the Editor: We read with great interest the article by Sethy et al1 providing an easy solution for the safe use of mobile phones in the clinics during the coronavirus disease 19 (COVID-19) pandemic. We have used the same solution since the beginning of the outbreak in our center, and yet, we believe some shortcomings of the proposed method need to be mentioned. Full-Text PDF
Relationship between particle size and lung retention time of intact solid lipid nanoparticle suspensions after pulmonary delivery
Authors: Zhengwei Huang, Ying Huang, Wenhua Wang, Fangqin Fu, Wenhao Wang, Shishuai Dang, Cheng Li, Cheng Ma, Xuejuan Zhang, Ziyu Zhao, Xin Pan, Chuanbin Wu
Journal: Journal of Controlled Release (2020)
Author Correction: The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling
Authors: Jin Jin, Yichuan Xiao, Jae-Hoon Chang, Jiayi Yu, Hongbo Hu, Robyn Starr, George C. Brittain, Mikyoung Chang, Xuhong Cheng, Shao-Cong Sun
Journal: Nature Immunology (2020)
Efficacy of 90Y-Ibritumomab Tiuxetan in the Older Population with Non-Hodgkin Lymphoma Pre-Treated with Rituximab-Based Regimens: A Single-Institution Experience
Authors: Vaibhav Agrawal, Smelser T. Diane, Jose I. Castillo, Kelly Raup, Girton D. Treanna, Scotty R. Collins, James O. Brady, Sharif S. Khan
Journal: Blood (2017)