tbuckley/cabot-search huggingface dataset:
Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury
Authors: Takuto Chiba, Débora M. Cerqueira, Yao Li, Andrew J. Bodnar, Elina Mukherjee, Katherine Pfister, Yu Leng Phua, Kai Shaikh, Brandon T. Sanders, Shelby L. Hemker, Patrick J. Pagano, Yijen L. Wu, Jacqueline Ho, Sunder Sims-Lucas
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Regulation of endothelial cells is important in many biologic processes, including development, organ function, and disease. The kidney vasculature is highly sensitive to hypoxic injury and has a limited capacity for repair. AKI as a result of decreased blood flow is common, and there are no current therapies. MicroRNAs are small noncoding RNAs that inhibit expression of target genes. Endothelial-derived miR-17∼92 is a cluster of microRNAs critical for endothelial function and repair during AKI in mice. Furthermore, pharmacologic treatment with mimics of the cluster mitigates AKI, promoting angiogenesis. These microRNAs are the first potential therapeutic target for kidney endothelial damage after AKI, and mimics may be broadly applicable to disease processes that involve endothelial injury. Background Damage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17 , -18a , -19a , -20a , -19b-1 , and -92a-1 ) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established. Methods Antibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout ( miR-17∼92 endo−/− ) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated. Results miR-17 , -18a , -20a , -19b , and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92 endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92 endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92 endo−/− after renal IRI and is a target of miR-18a and miR-19a/b . miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate. Conclusions These data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.
Explaining covid-19 performance: what factors might predict national responses?
Authors: Fran Baum, Toby Freeman, Connie Musolino, Mimi Abramovitz, Wim De Ceukelaire, Joanne Flavel, Sharon Friel, Camila Giugliani, Philippa Howden-Chapman, Nguyen Thanh Huong, Leslie London, Martin McKee, Jennie Popay, Hani Serag, Eugenio Villar
Journal: BMJ (2021)

<i>Correspondence to: F Baum</i>fran.baum@flinders.edu.au <b>Fran Baum and colleagues</b> discuss the factors that affected prediction of the success of national responses to covid-19 and will influence future pandemic preparedness
Mediastinal Recurrence of Uterine Cervix Cancer on 18F-FDG PET/CT
Authors: Cristina Soldevila-Lozano, Aida Sabaté-Llobera, Javier-Jesús Robles-Barba, Judit Mestres-Martí, Montserrat Cortés-Romera
Journal: Clinical Nuclear Medicine (2021)

We report the case of a 64-year-old woman with a mediastinal relapse of a uterine cervix cancer with positive human papillomavirus, an unusual site of recurrence. She consulted because of solid and liquid dysphagia of sudden appearance. Endoscopic study and non-contrast-enhanced CT showed intraluminal esophageal stenosis with a retrograde esophageal distension. 18F-FDG PET/CT demonstrated an infiltrating hypermetabolic lesion in posterior mediastinum, middle and lower esophagus, and stomach, with no signs of local or regional relapse of the uterine neoplasm.
Keto form of curcumin derivatives strongly binds to Aβ oligomers but not fibrils
Authors: Daijiro Yanagisawa, Tomoko Kato, Hiroyasu Taguchi, Nobuaki Shirai, Koichi Hirao, Takayuki Sogabe, Takami Tomiyama, Keizo Gamo, Yukie Hirahara, Masaaki Kitada, Ikuo Tooyama
Journal: Biomaterials (2021)

The accumulation of β-amyloid (Aβ) aggregates in the brain occurs early in the progression of Alzheimer's disease (AD), and non-fibrillar soluble Aβ oligomers are particularly neurotoxic. During binding to Aβ fibrils, curcumin, which can exist in an equilibrium state between its keto and enol tautomers, exists predominantly in the enol form, and binding activity of the keto form to Aβ fibrils is much weaker. Here we described the strong binding activity the keto form of curcumin derivative Shiga-Y51 shows for Aβ oligomers and its scant affinity for Aβ fibrils. Furthermore, with imaging mass spectrometry we revealed the blood-brain barrier permeability of Shiga-Y51 and its accumulation in the cerebral cortex and the hippocampus, where Aβ oligomers were mainly localized, in a mouse model of AD. The keto form of curcumin derivatives like Shiga-Y51 could be promising seed compounds to develop imaging probes and therapeutic agents targeting Aβ oligomers in the brain.
Imaging Tumor-Infiltrating Lymphocytes in Brain Tumors with [64Cu]Cu-NOTA-anti-CD8 PET
Authors: Veronica L. Nagle, Kelly E. Henry, Charli Ann J. Hertz, Maya S. Graham, Carl Campos, Luis F. Parada, Neeta Pandit-Taskar, Andrea Schietinger, Ingo K. Mellinghoff, Jason S. Lewis
Journal: Clinical Cancer Research (2021)

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Various immunotherapeutic approaches to improve patient survival are being developed, but the molecular mechanisms of immunotherapy resistance are currently unknown. Here, we explored the ability of a humanized radiolabeled CD8-targeted minibody to noninvasively quantify tumor-infiltrating CD8-positive (CD8+) T cells using PET.We generated a peripheral blood mononuclear cell (PBMC) humanized immune system (HIS) mouse model and quantified the absolute number of CD8+ T cells by flow cytometry relative to the [64Cu]Cu-NOTA-anti-CD8 PET signal. To evaluate a patient-derived orthotopic GBM HIS model, we intracranially injected cells into NOG mice, humanized cohorts with multiple HLA-matched PBMC donors, and quantified CD8+ tumor-infiltrating lymphocytes by IHC. To determine whether [64Cu]Cu-NOTA-anti-CD8 images brain parenchymal T-cell infiltrate in GBM tumors, we performed PET and autoradiography and subsequently stained serial sections of brain tumor tissue by IHC for CD8+ T cells.Nontumor-bearing NOG mice injected with human PBMCs showed prominent [64Cu]Cu-NOTA-anti-CD8 uptake in the spleen and minimal radiotracer localization to the normal brain. NOG mice harboring intracranial human GBMs yielded high-resolution PET images of tumor-infiltrating CD8+ T cells. Radiotracer retention correlated with CD8+ T-cell numbers in spleen and tumor tissue. Our study demonstrates the ability of [64Cu]Cu-NOTA-anti-CD8 PET to quantify peripheral and tumor-infiltrating CD8+ T cells in brain tumors.Human CD8+ T cells infiltrate an orthotopic GBM in a donor-dependent manner. Furthermore, [64Cu]Cu-NOTA-anti-CD8 quantitatively images both peripheral and brain parenchymal human CD8+ T cells.
Correspondence on ‘A pilot study of tofacitinib for refractory Behçet’s syndrome’
Authors: Jun Zou, Chen-Hong Lin, Yan Wang, Yan Shen, Jian-Long Guan
Journal: Annals of the Rheumatic Diseases (2021)

We carefully read the recent study by Liu et al on the effectiveness of tofacitinib for refractory Behcet’s syndrome (BS).1 In total, 13 patients with BS were enrolled, including 5 cases with vascular involvement, 7 with gastrointestinal (GI) ulcers and one suffering polyarthritis. As an add-on approach, tofacitinib improved the outcomes in all patients with vascular lesions, but unchanged or worsened in 5/7 GI involvement cases. Their observation give support to the hypothesis that BS is not an independent disease, but a heterogeneous and multisystemic complex syndrome.2 Different major organ involvements, vascular and GI involvement could link to its unique underlying immunopathological mechanisms, which led to radical treatment responses.3 In their study, the only manifestation of ocular involvement was scleritis in one patient with polyarthritis, which is not a specific ophthalmological feature of BS. Notably, uveitis is one of the specific features of ocular involvement in patients with BS,4 which may lead to visual loss in up to 25% of patients in spite of biological agents.5 Here, we reported the efficacy and safety profile of …
SAT0028 Late onset ankylosing spondylitis-clinical and radiological manifestations
Authors: DK Kerimovic-Morina, D Jablanovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To compare clinical and radiological manifestations of late onset ankylosing spondylitis (LOAS: &gt;51 yrs) with classical onset ankylosing spondylitis (COAS:21–30 yrs). <h3>Methods</h3> We identified twenty-nine (2,0%) pts with LOAS out of 1434 AS pts and they were matched for sex and disease duration with COAS pts. All pts fulfilled the diagnostic criteria of AS of the European Spondyloarthropathy study group (ESSG). Evaluation included clinical examination: inflammatory pain, spinal mobility (Schober test, chest expansion), peripheral arthritis and enthesitis, acute uveitis, family history; laboratory (ESR, HLA-B27); radiographs of the sacroiliac joints (SIJ), anteroposterior and lateral spine and affected peripheral joints). Statistical analysis was performed using Spearman rank correlation test and X- test. <h3>Results</h3> Analysis revealed no significant differences (p &gt; 0.005) in clinical manifestations between twenty-nine (27 m,2 f) pts with LOAS(mean age and disease duration 56,0 yrs (range 53–62) and 8, o yrs (range 8–12) respectively) and twenty-nine pts with COAS(mean age at onset 24,2 yrs and mean disease duration 7,8 yrs (range 4–16) rescpectively), except for spinal mobility (p &lt; 0,005). No significant differences (p &gt; 0,005) were found between groups of the laboratory findings. All pts had bilateral sacroiliitis. The results are shown in the Table 1. The radiographic changes in SIJ (grade III and IV) were more frequent in LOAS pts than in COAS (p &lt; 0,005), as well as on the spine (p &lt; 0,005). The radiographic progression in the SIJ and the spine were more rapid in LOAS pts than in COAS pts, the difference was statistically significant (p &lt; 0,005). <h3>Conclusion</h3> According to our experince the onset of ankylosing spondylitis is uncommon after 51-st yr; LOAS and COAS have similar clinical manifestations; LOAS had clinically more progressive course and rapid radiopraphic progression leading to severe changes in the SIJ and spine (p &lt; 0,005). the possible explanation for the difference observed is a clinically asymptomatic or ?silent? ankylosing spondylitis in patients with late onset of disease. <h3>Reference</h3> Caplanne D, Tubach F, Marie Le Parc J. Late onset spondyloarthropathy: Clinical and biologycal comparation with early onset patients. Ann Rheum Dis. 1997;56:176–9
Abstract IA20: A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest
Authors: Makoto T. Hayashi, Jan Karlseder
Journal: Cancer Research (2014)

Abstract Telomere shortening and disruption of telomeric components are pathways that induce telomere deprotection. Here we describe another pathway, where prolonged mitotic arrest induces damage signals at telomeres in human cells. Exposure to microtubule drugs, kinesin inhibitors, proteasome inhibitors or the disruption of proper chromosome cohesion resulted in the formation of damage-foci at telomeres. Induction of mitotic telomere deprotection coincided with dissociation of TRF2 (Telomere Repeat binding Factor 2) from telomeres, telomeric 3′-overhang degradation and ATM (Ataxia Telangiectasia Mutated) activation, and could be suppressed by TRF2 overexpression or inhibition of Aurora B kinase. Normal cells that escape from prolonged mitotic arrest halted in the following G1 phase, whereas cells lacking p53 continued to cycle and became aneuploid. We propose a telomere dependent mitotic duration monitoring system that reacts to improper progression through mitosis and will discuss the molecular details and implications of this pathway. Citation Format: Makoto T. Hayashi, Jan Karlseder. A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA20. doi:10.1158/1538-7445.CANSUSC14-IA20
Advances in Micro/Nanoporous Membranes for Biomedical Engineering
Authors: Meilin Sun, Kai Han, Rui Hu, Dan Liu, Wenzhu Fu, Wenming Liu
Journal: Advanced Healthcare Materials (2021)

Abstract Porous membrane materials at the micro/nanoscale have exhibited practical and potential value for extensive biological and medical applications associated with filtration and isolation, cell separation and sorting, micro‐arrangement, in‐vitro tissue reconstruction, high‐throughput manipulation and analysis, and real‐time sensing. Herein, an overview of technological development of micro/nanoporous membranes (M/N‐PMs) is provided. Various membrane types and the progress documented in membrane fabrication techniques, including the electrochemical‐etching, laser‐based technology, microcontact printing, electron beam lithography, imprinting, capillary force lithography, spin coating, and microfluidic molding are described. Their key features, achievements, and limitations associated with micro/nanoporous membrane (M/N‐PM) preparation are discussed. The recently popularized applications of M/N‐PMs in biomedical engineering involving the separation of cells and biomolecules, bioparticle operations, biomimicking, micropatterning, bioassay, and biosensing are explored too. Finally, the challenges that need to be overcome for M/N‐PM fabrication and future applications are highlighted.
Implications for law of a unified behavioral science
Authors: Owen D. Jones
Journal: Behavioral and Brain Sciences (2007)

The argument for unifying behavioral sciences can be enhanced by highlighting concrete, vivid, and useful benefits that coherent behavioral models could provide. Shifting sets of behavioral assumptions underlie every legal system's efforts to modify behaviors by changing incentives in the legal environment. Consequently, where those assumptions are flawed, improved behavioral models could improve law's effectiveness and efficiency in regulating behavior.
Abstract 15660: Propranolol Inhibits Late Sodium Current in Long-QT Syndrome Type 3 Human Induced Pluripotent Stem Cell-drived Myocyte Model
Authors: Sayako Hirose, Takeru Makiyama, Dario Melgari, Jie Wu, Fumika Yokoi, Yimin Wuriyanghai, Yuta Yamamoto, Hirohiko Kohjitani, Suguru Nishiuchi, Takeshi Harita, Mamoru Hayano, Jun Yoshimoto, Seiko Ohno, Yoshinori Yoshida, Minoru Horie, Takeshi Kimura
Journal: Circulation (2017)

Backgound: Long-QT syndrome type 3 (LQT3) is caused by gain-of-function mutations in SCN5A, encoding the α subunit of the cardiac voltage-gated sodium channel. LQT3 patients present bradycardia and...
Sleep disorders on a psychiatric consultation service
Authors: R M Berlin, G L Litovitz, M A Diaz, S W Ahmed
Journal: American Journal of Psychiatry (1984)

Of 100 consecutive patients on a psychiatric consultation service, 80 had sleep disorders; 72 had insomnia. Disturbed sleep was not mentioned in the records of 54% of the 80 patients, indicating a need for more physician education in sleep disorders.
Combination Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma
Authors: Annie Kanchan Baa, Sameer Rastogi
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
OP0098 The jak3 promoter region is stimulated by t cell activation and contains essential ap-1 and ets-1 elements
Authors: M Aringer, DM Frucht, M Chen, M Centola, JJ O’Shea
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Janus Kinase 3 (Jak3) is a non-receptor tyrosine kinase essential for interleukin- (IL-) 2, 4, 7, 9, and 15 signalling. In T lymphocytes, Jak3 expressed is clearly increased upon T cell activation. The regulatory regions of the Jak3 promoter, however, are unknown. <h3>Objectives</h3> We therefore decided to characterise the promoter region of Jak3. <h3>Methods</h3> A 5´race procedure was used to detect the beginning of Jak3 cDNA derived from both the Jurkat T cell line and an NK cell line (NK3.3). All sequencing was performed on an ABI 377 automated sequencer using DNA amplified by PCR and the ABI Big Dye terminator kit. Putative promoter pieces were amplified by PCR and subcloned into a luciferase vector. In addition, site-directed mutagenesis was used to change two AP-1 sites and a putative Stat binding site within the core promoter region. Jurkat T cells were transfected both with these constructs and a beta-galactosidase vector for normalisation; both activities were sequentially read on a luminometer using the Tropix Dual Light kit. <h3>Results</h3> All Jak3 mRNA started 5´ of a 3515 basepair intron; the first basepair of the longest mRNA species found was denominated as +1. The 1039 basepair DNA region 5` of the mRNA start (-1013/+27) worked as a (TATA-less) promoter and could be activated by PMA, PHA, or immobilised anti-CD3, but not anti-CD28. As expected, the promoter did not work in the &nbsp;reverse direction. Truncation constructs showed the active region situated within a 267 basepair (-240/+27) region, the core promoter was positioned between ?74 and ?16. Within this region, that contained also an SP-1 site, a double-AP1 site, but not the potential Stat site in between, was of major importance, as demonstrated by targeted point mutation. Surrounding the core promoter, two Ets-1 consensus elements had significant (around 6-fold) enhancer activity. <h3>Conclusion</h3> The Jak3 promoter is situated around 3500 basepairs 5`of its ATG-codon. The promoter can be activated by T cell receptor crosslinking and contains an active double AP-1 binding site and Ets-1 consensus elements that work as significant enhancers. This may lead to improved IL-2 (or ?4, -7- or ?15) signalling in disease states where T lymphocytes are being activated.
Robust Bioinformatics Approach for Identifying Novel AML LSC Targets: Putative Role of Galectin-1 in the Immune-Microenvironment
Authors: Shelley Herbrich, Peter P. Ruvolo, Vivian Ruvolo, Keith Baggerly, Gheath Alatrash, Michael Andreeff, Marina Konopleva
Journal: Blood (2017)
The changing context of hepatitis D
Authors: Mario Rizzetto, Saeed Hamid, Franco Negro
Journal: Journal of Hepatology (2021)

The global epidemiology of hepatitis D is changing with the widespread implementation of vaccination against hepatitis B. In high-income countries that achieved optimal control of HBV, the epidemiology of hepatitis D is dual, consisting of an ageing cohort of domestic patients with advanced liver fibrosis who represent the end stage of the natural history of HDV, and of a younger generation of immigrants from endemic countries who account for the majority of new infections. As observed in Europe in the 1980s, the distinctive clinical characteristic of chronic hepatitis D in endemic countries is the accelerated progression to cirrhosis and hepatocellular carcinoma. Despite some recent progress, the therapeutic management of HDV remains unsatisfactory, as most patients are not cured of HDV with currently available medicines. This review article describes the current epidemiology and clinical features of chronic hepatitis D, based on the literature published in the last 10 years.
Insights into the Links between MYC and 3D Chromatin Structure and Epigenetics Regulation: Implications for Cancer Therapy
Authors: Fatemeh Amjadi-Moheb, Alireza Paniri, Haleh Akhavan-Niaki
Journal: Cancer Research (2021)

MYC is embedded in the transcriptional oasis of the 8q24 gene desert. A plethora of genomic elements has roles in MYC aberrant expression in cancer development by interacting with transcription factors and epigenetics regulators as well as altering the structure of chromatin at the MYC locus and tissue-specific long-range enhancer-promoter contacts. Furthermore, MYC is a master regulator of several human cancers by modulating the transcription of numerous cancer-related genes through epigenetic mechanisms. This review provides a comprehensive overview of the three-dimensional genomic organization around MYC and the role of epigenetic machinery in transcription and function of MYC as well as discusses various epigenetic-targeted therapeutic strategies in MYC-driven cancers.