tbuckley/cabot-search huggingface dataset:
IL‐23‐Th17軸による自己抗体活性の調節は自己免疫疾患の発症を決定する
Authors: Pfeifle Rene, Rothe Tobias, Ipseiz Natacha, Scherer Hans U, Culemann Stephan, Harre Ulrike, Ackermann Jochen A, Seefried Martina, Kleyer Arnd, Uderhardt Stefan, Haugg Benjamin, Hueber Axel J, Daum Patrick, Heidkamp Gordon F, GE Changrong, Boehm Sybille, Lux Anja, Schuh Wolfgang, Magorivska Iryna, Nandakumar Kutty S, Loennblom Erik, Becker Christoph, Dudziak Diana, Wuhrer Manfred, Romboutset Yoann, Koeleman Carolien A, Toes Rene, Winkler Thomas H, Holmdahl Rikard, Herrmann Martin, Blueml Stephan, Nimmerjahn Falk, Schett Georg, Kroenke Gerhard
Journal: Nature Immunology (2017)
Concerns on glucocorticoid use for Japanese patients with established rheumatoid arthritis
Authors: Hiroshi Oiwa
Journal: Annals of the Rheumatic Diseases (2017)

I read with great interest the recommendation for the management of rheumatoid arthritis (RA) by the European League Against Rheumatism (EULAR), especially the recommendation regarding glucocorticoid use: ‘Short-term glucocorticoids should be considered when initiating or changing conventional synthetic disease-modifying antirheumatic drugs (DMARDs), in different dose regimens and routes of administration, but should be tapered as rapidly as clinically feasible’.1 This recommendation was primarily supported by randomised controlled studies that suggested the efficacy and acceptable safety of glucocorticoids in early RA compared with placebo.1 2 However, I …
Abstract 14568: Three-year Restenosis Rate and Its Predictors After Endovascular Therapy for Leriche Syndrome
Authors: Kiyonori Nanto, Osamu Iida, Masahiko Fujihara, Yusuke Tomoi, Yoshimitsu Soga, Masashi Fujita, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Takashi Kanda, Takuya Tsujimura, Akihiro Sunaga, Koji Yanaka, Shota Okuno, Yasuhiro Matsuda, Takuya Ohashi, Masaaki Uematsu
Journal: Circulation (2016)

Introduction: Although current guidelines recommend surgical revascularization as the first-line therapy for chronic total occlusion of the abdominal aorta (Leriche syndrome), endovascular therapy ...
Prevalence of Pathogenic Copy Number Variation in Adults With Pediatric-Onset Epilepsy and Intellectual Disability
Authors: Felippe Borlot, Brigid M. Regan, Anne S. Bassett, D. James Stavropoulos, Danielle M. Andrade
Journal: JAMA Neurology (2017)

Copy number variation (CNV) is an important cause of neuropsychiatric disorders. Little is known about the role of CNV in adults with epilepsy and intellectual disability.To evaluate the prevalence of pathogenic CNVs and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability.In this cross-sectional study, genome-wide microarray was used to evaluate a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014. The inclusion criteria were (1) pediatric seizure onset with ongoing seizure activity in adulthood, (2) intellectual disability of any degree, and (3) no structural brain abnormalities or metabolic conditions that could explain the seizures.DNA screening was performed using genome-wide microarray platforms. Pathogenicity of CNVs was assessed based on the American College of Medical Genetics guidelines. The Residual Variation Intolerance Score was used to evaluate genes within the identified CNVs that could play a role in each patient's phenotype.Of the 2335 patients, 143 probands were investigated (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female). Twenty-three probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb). Five of the 23 probands with positive results (21.7%) had more than 1 CNV reported. Parental testing revealed de novo CNVs in 11 (47.8%), with CNVs inherited from a parent in 4 probands (17.4%). Sixteen of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy. Eight nonrecurrent rare CNVs that overlapped 1 or more genes associated with intellectual disability, autism, and/or epilepsy were identified: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication. Five genes are of particular interest given their potential pathogenicity in the corresponding phenotypes and least tolerability to variation: ABAT, KIAA2022, COL4A1, CACNA1C, and SMARCA2. ABAT duplication was associated with Lennox-Gastaut syndrome and KIAA2022 deletion with Jeavons syndrome.The high prevalence of pathogenic CNVs in this study highlights the importance of microarray analysis in adults with unexplained childhood-onset epilepsy and intellectual disability. Additional studies and comparison with similar cases are required to evaluate the effects of deletions and duplications that overlap specific genes.
Investigation of cardiac fibroblasts using myocardial slices
Authors: Filippo Perbellini, Samuel A Watson, Martina Scigliano, Samha Alayoubi, Sebastian Tkach, Ifigeneia Bardi, Nicholas Quaife, Christopher Kane, Neil P Dufton, André Simon, Markus B Sikkel, Giuseppe Faggian, Anna M Randi, Julia Gorelik, Sian E Harding, Cesare M Terracciano
Journal: Cardiovascular Research (2017)

Abstract Aims Cardiac fibroblasts (CFs) are considered the principal regulators of cardiac fibrosis. Factors that influence CF activity are difficult to determine. When isolated and cultured in vitro, CFs undergo rapid phenotypic changes including increased expression of α-SMA. Here we describe a new model to study CFs and their response to pharmacological and mechanical stimuli using in vitro cultured mouse, dog and human myocardial slices. Methods and results Unloading of myocardial slices induced CF proliferation without α-SMA expression up to 7 days in culture. CFs migrating onto the culture plastic support or cultured on glass expressed αSMA within 3 days. The cells on the slice remained αSMA(−) despite transforming growth factor-β (20 ng/ml) or angiotensin II (200 µM) stimulation. When diastolic load was applied to myocardial slices using A-shaped stretchers, CF proliferation was significantly prevented at Days 3 and 7 (P &lt; 0.001). Conclusions Myocardial slices allow the study of CFs in a multicellular environment and may be used to effectively study mechanisms of cardiac fibrosis and potential targets.
Almost 200 000 children under 5 died from TB in 2015
Authors: Sophie Cousins
Journal: BMJ (2017)

Nearly 200 000 children aged under 5 died from tuberculosis (TB) in 2015, mostly in sub-Saharan Africa and southeast Asia, a study has shown.1

The mathematical modelling, which showed death rates from TB in under 5s for the first time, found that 239 000 children aged 14 and under died of TB in 2015. Some 80% of these (191 000) were aged under 5.

The researchers, from the University of Sheffield, UK, said that the high number of deaths implied “that …
Neurodevelopmental Outcome in Relation to Treatment of Patent Ductus Arteriosus
Authors: Jonathan L. Slaughter, Mark A. Klebanoff
Journal: JAMA Pediatrics (2017)

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
Patient Decision Aids to Engage Adults in Treatment or Screening Decisions
Authors: Dawn Stacey, France Légaré, Krystina B. Lewis
Journal: JAMA (2017)

<h3>Clinical Question</h3> Are patient decision aids (PtDAs) associated with (1) improved decision quality defined as a decision informed by the evidence and a value-based decision; (2) improved decision-making processes defined as feeling informed, defining clear values related to the decision, and active participation in making the decision; and (3) better patient and health system outcomes compared with either usual care or a non-PtDA intervention? <h3>Bottom Line</h3> Patient decision aids are associated with improved decision quality and decision-making processes without worse patient or health system outcomes.
Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive Impairment
Authors: Yue Leng, Claire T. McEvoy, Isabel E. Allen, Kristine Yaffe
Journal: JAMA Neurology (2017)

Growing evidence suggests an association between sleep-disordered breathing (SDB) and cognitive decline in elderly persons. However, results from population-based studies have been conflicting, possibly owing to different methods to assess SDB or cognitive domains, making it difficult to draw conclusions on this association.To provide a quantitative synthesis of population-based studies on the relationship between SDB and risk of cognitive impairment.PubMed, EMBASE, and PsychINFO were systematically searched to identify peer-reviewed articles published in English before January 2017 that reported on the association between SDB and cognitive function.We included cross-sectional and prospective studies with at least 200 participants with a mean participant age of 40 years or older.Data were extracted independently by 2 investigators. We extracted and pooled adjusted risk ratios from prospective studies and standard mean differences from cross-sectional studies, using random-effect models. This meta-analysis followed the PRISMA guidelines and also adhered to the MOOSE guidelines.Cognitive outcomes were based on standard tests or diagnosis of cognitive impairment. Sleep-disordered breathing was ascertained by apnea-hypopnea index or clinical diagnosis.We included 14 studies, 6 of which were prospective, covering a total of 4 288 419 men and women. Pooled analysis of the 6 prospective studies indicated that those with SDB were 26% (risk ratio, 1.26; 95% CI, 1.05-1.50) more likely to develop cognitive impairment, with no evidence of publication bias but significant heterogeneity between studies. After removing 1 study that introduced significant heterogeneity, the pooled risk ratio was 1.35 (95% CI, 1.11-1.65). Pooled analysis of the 7 cross-sectional studies suggested that those with SDB had slightly worse executive function (standard mean difference, -0.05; 95% CI, -0.09 to 0.00), with no evidence of heterogeneity or publication bias. Sleep-disordered breathing was not associated with global cognition or memory.Sleep-disordered breathing is associated with an increased risk of cognitive impairment and a small worsening in executive function. Further studies are required to determine the mechanisms linking these common conditions and whether treatment of SDB might reduce risk of cognitive impairment.
Reframing the Opioid Epidemic as a National Emergency
Authors: Lawrence O. Gostin, James G. Hodge, Sarah A. Noe
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
ナノトポグラフィーは骨格幹細胞の自己再生および多分化能に関与する細胞周期の変化を制御する【Powered by NICT】
Authors: C Y Lee Louisa, Gadegaard Nikolaj, C de Andres Maria, Turner Lesley-Anne, V Burgess Karl, J Yarwood Stephen, Wells Julia, Salmeron-Sanchez Manuel, Meek Dominic, O C Oreffo Richard, J Dalby Matthew
Journal: Biomaterials (2017)
The role of amyloid beta clearance in cerebral amyloid angiopathy: more potential therapeutic targets
Authors: Xue-mei Qi, Jian-fang Ma
Journal: Translational Neurodegeneration (2017)

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid β-protein (Aβ) in the leptomeningeal and cortical blood vessels, which is an age-dependent risk factor for intracerebral hemorrhage (ICH), ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment. However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms. In recent years, many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer's disease (AD), and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA. So decreased clearance of Aβ in blood vessels plays a crucial role in the development of CAA and AD, and identification of the molecular pathways involved will provide new targets for treatment. In this review, we mainly describe the mechanisms of Aβ clearance through vessels, especially in terms of some proteins and receptors involved in this process.
A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment
Authors: Frederic Sierro, Maximilien Evrard, Simone Rizzetto, Michelle Melino, Andrew J. Mitchell, Manuela Florido, Lynette Beattie, Shaun B. Walters, Szun Szun Tay, Bo Lu, Lauren E. Holz, Ben Roediger, Yik Chun Wong, Alessandra Warren, William Ritchie, Claire McGuffog, Wolfgang Weninger, David G. Le Couteur, Florent Ginhoux, Warwick J. Britton, William R. Heath, Bernadette M. Saunders, Geoffrey W. McCaughan, Fabio Luciani, Kelli P.A. MacDonald, Lai Guan Ng, David G. Bowen, Patrick Bertolino
Journal: Immunity (2017)
A phase 1 multicenter clinical trial of alemtuzumab and CHOP chemotherapy for peripheral T-cell lymphomas.
Authors: Rena Buckstein, Michael Crump, Graeme A Fraser, Matthew C. Cheung, Eugenia Piliotis, Kevin Imrie, Vishal Kukreti, John Kuruvilla, Ralph M. Meyer, Jolanta Windsor, Gregory Russell Pond, Kathleen I. Pritchard, Mark Norman Levine
Journal: Journal of Clinical Oncology (2014)

8551 Background: Alemtuzumab is an anti CD52 monoclonal antibody with single agent activity in relapsed peripheral T cell lymphomas (PTCL), but the optimal dose/schedule to combine with chemotherapy is unknown. Methods: The primary objectives of this phase 1 study were to establish the maximally tolerated dose (MTD) and pharmacokinetics (PK) of alemtuzumab combined with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) q21days. The MTD with highest trough levels would define the recommended phase II/III dose. Patient eligibility included: > age 18, untreated CD52+ PTCL, stage 2-4, measurable disease and adequate organ function. Alemtuzumab was given subcutaneously in 1 of 4 schedules using a 3+3 design with CHOP chemotherapy: 1) 10 mg day 1; 2) 10 mg weekly days 1, 8, 15; 3) 30 mg day 1; 4) 60 mg day 1. Trough PK were measured on day 1 of each 21d CHOP cycle. Results: 20 patients were enrolled; histology: AILD (n=7), PTCL NOS (n=6), ALK 1–ALCL (n=3), subpanniculitic (n=2), hepatosplenic (n=1) and enteropathy associated (n=1). DLT’s necessitated dose expansion of dose level 2 (fatal TB reactivation) and 4 (grade 4 thrombocytopenia). The MTD was not reached. The most common hematologic toxicities were lymphopenia (65% grade 3-4), neutropenia (55% grade 3-4) and febrile neutropenia (25%). Ten (50%) patients developed asymptomatic CMV reactivations at a median of 39 days (range 4-99) treated with valganciclovir. Two patients developed fungal pneumonias. Of 18 evaluable for response, the overall response rate was 65% (CR/Cru (n=7), PR (n=6)). With a median f/u of 28 months (range 1.3-77.4), 10 patients (52%) have relapsed or progressed and 4 (21%) have died. Median OS has not been reached and median PFS is 23 months. Peripheral blood CD3+ T cells declined by 80-100% from baseline and recovered in 55% of patients at a median time of 15 mos. Mean trough alemtuzumab levels by dose level were 1) 57, 2) 464, 3) 124 and 4) 501 ng/ml. Conclusions: Weekly SC alemtuzumab 10 mg achieves trough levels comparable with 60 mg q21d when given with CHOP. With close monitoring, toxicity was manageable and CMV disease was not seen. These doses with CHOP should be tested in patients with peripheral T cell lymphoma. Funded by NCIC grant#16398. Clinical trial information: NCT00363090.
Magnetic cationic liposome therapeutics suppresses tumor growth and metastasis
Authors: Suman Dandamudi, Robert Campbell
Journal: Cancer Research (2008)

5720   Introduction: Cationic liposomes preferentially target tumor vessels, but heterogeneously. To target tumor vasculature more uniformly we seek to combine the electrostatic properties of cationic liposomes with the strength of an external magnetic field (EMF). We studied the effect of external magnet (0.4 tesla) on cellular interactions of MAG-C cationic liposomes with melanoma (B16-F10) and endothelial cells (HMEC-1). We also characterized the drug loaded MAG-C cationic liposomes for their incorporation efficiency and cell growth inhibitory properties. We then determined the influence of external magnet on tumor accumulation of MAG-C cationic liposomes in melanoma bearing SCID mice. Finally, we performed tumor response studies with vinblastine loaded MAG-C PCLs in melanoma bearing SCID mice with and without external magnet (1.2 tesla).  Methods: DIC/ fluorescence and Transmission Electron Microscopy (TEM) were used to evaluate cellular uptake of liposomes. Cell viability was measured by SRB assay. HPLC experiments were performed to determine incorporation efficiencies. Intravital microscopy using dorsal skin fold chambers was used to observe the interaction of liposomes with tumor blood vessels.  Results: Higher cellular interaction of magnetic electroneutral liposomes was observed in presence of external magnet (0.4 T, exposure time-60 min) with both B16-F10 (7.25 ± 0.19%) and HMEC-1 (20.18 ± 0.51%) compared with B16-F10 (4.55 ± 1.28%) and HMEC-1 (8.8 ± 1.87%) in absence of magnet. Fluorescence microscopy and TEM showed perinuclear localization of magnetic cationic liposomes in cells. Inclusion of MAG-C at lower concentrations (0.5 mg/ml) in cationic liposomes did not alter the incorporation efficiency of lipophilic drug etoposide, but decreased at higher concentration (2.5 mg/ml) from 78 ± 6.03% to 44 ± 4.26%. However, for hydrophilic drug vinblastine the incorporation efficiency decreased from 32 ± 3.61% to 21 ± 0.11% with the inclusion of MAG-C (0.5 mg/ml); no further decrease was observed with 2.5 mg/ml. Etoposide and vinblastine showed greater cytotoxicity against HMEC-1 than B16-F10. The cytotoxic effect of drugs loaded in cationic liposomes was not altered by the incorporation of MAG-C. Intravital microscopy showed accumulation of magnetic-PCLs along tumor vasculature; maximum retention of magnetic cationic liposomes in tumors was observed 1hr following exposure to external magnet. Finally, intravenous administration of vinblastine-loaded MAG-C PCLs in the presence of external magnet demonstrated significant antitumor activity when compared to no magnet. H&E staining revealed fewer tumor nodules in metastatic sites (i.e., liver, spleen, pleural cavity) in animals treated with vinblastine-loaded MAG-C PCLs compared to controls.  Conclusions: The results suggest that the combination of magnetic cationic liposomes with the strength of an EMF is a promising approach for clinical cancer therapy.
Bias Among Peer Reviewers
Authors: Adam C. Adler, Stephen A. Stayer
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
MicroRNA‐337‐3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation
Authors: Céline Demarez, Claude Gérard, Sabine Cordi, Alexis Poncy, Younes Achouri, Nicolas Dauguet, David A. Rosa, Patrick T. Gunning, Isabelle Manfroid, Frédéric P. Lemaigre
Journal: Hepatology (2017)

Transcriptional networks control the differentiation of the hepatocyte and cholangiocyte lineages from embryonic liver progenitor cells and their subsequent maturation to the adult phenotype. However, how relative levels of hepatocyte and cholangiocyte gene expression are determined during differentiation remains poorly understood. Here, we identify microRNA (miR)-337-3p as a regulator of liver development. miR-337-3p stimulates expression of cholangiocyte genes and represses hepatocyte genes in undifferentiated progenitor cells in vitro and in embryonic mouse livers. Beyond the stage of lineage segregation, miR-337-3p controls the transcriptional network dynamics of developing hepatocytes and balances both cholangiocyte populations that constitute the ductal plate. miR-337-3p requires Notch and transforming growth factor-β signaling and exerts a biphasic control on the hepatocyte transcription factor hepatocyte nuclear factor 4α by modulating its activation and repression. With the help of an experimentally validated mathematical model, we show that this biphasic control results from an incoherent feedforward loop between miR-337-3p and hepatocyte nuclear factor 4α.Our results identify miR-337-3p as a regulator of liver development and highlight how tight quantitative control of hepatic cell differentiation is exerted through specific gene regulatory network motifs. (Hepatology 2018;67:313-327).