tbuckley/cabot-search huggingface dataset:
Association of JNC-8 and SPRINT Systolic Blood Pressure Levels With Cognitive Function and Related Racial Disparity
Authors: Ihab Hajjar, Kristine J. Rosenberger, Ambar Kulshreshtha, Hilsa N. Ayonayon, Kristine Yaffe, Felicia C. Goldstein
Journal: JAMA Neurology (2017)

The Eighth Joint National Committee (JNC-8) recommended treating systolic blood pressure (SBP) to a target below 150 mm Hg in older adults, whereas data from the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that a SBP level of lower than 120 mm Hg decreases cardiovascular event rates. Target SBP guidelines have not addressed the potential that black patients may have greater morbidity and mortality from hypertension, especially with regard to cognitive outcomes. The association of these discordant SBP targets with cognition and differences by race have not been systematically evaluated in the same population.To assess the long-term outcomes of the various recommended SBP levels and to determine if racial differences exist based on long-term cognitive trajectories.A total of 1657 cognitively intact older adults receiving treatment for hypertension were studied from 1997 to 2007 in the Health Aging and Body Composition study. Data analysis was conducted from October 1, 2016, to January 1, 2017.Cognition was assessed using the Modified Mini-Mental State Examination (3MSE) 4 times and the Digit Symbol Substitution Test (DSST) 5 times. At each visit, participants were classified as having an SBP level of 120 mm Hg or lower, 121 to 139 mm Hg, 140 to 149 mm Hg, or 150 mm Hg or higher based on the mean SBP level of 2 seated readings. Mixed models assessed the association of SBP levels with 10-year cognitive trajectories. The impact of race was tested using a race interaction term.During the 10-year study period, among the 1657 individuals (908 women and 784 black patients; mean [SE] age, 73.7 [0.1] years), there was a differential decrease in 3MSE and DSST scores by the SBP levels, with the greatest decrease in the group with SBP levels of 150 mm Hg or higher (adjusted decrease was 3.7 for 3MSE and 6.2 for DSST) and the lowest decrease in the group with SBP levels of 120 mm Hg or lower (adjusted decrease was 3.0 for 3MSE and 5.0 for DSST) (P < .001 for both). Compared with white patients, black patients had a greater difference between the higher and lower SBP levels in the decrease in cognition; adjusted differences between the group with SBP levels of 150 mm Hg or higher and the group with SBP levels of 120 mm Hg or lower were -0.05 in white patients and -0.08 in black patients for 3MSE (P = .03) and -0.07 in white patients and -0.13 in black patients for DSST (P = .05).For patients 70 years of age or older receiving treatment for hypertension, a SPRINT SBP level of 120 mm Hg or lower was not associated with worsening cognitive outcome and may be superior to the JNC-8 target for cognition. Lower SBP treatment levels may result in improved cognition in black patients.
MIを標的としたVEGF送達システムはMSCとlayer‐by‐layer自己集合の親和性に基づく血管新生および心機能を改善する【Powered by NICT】
Authors: Liu Ge, Li Li, Huo Da, Li Yanzhao, Wu Yangxiao, Zeng Lingqing, Cheng Panke, Xing Malcolm, Zeng Wen, Zhu Chuhong
Journal: Biomaterials (2017)
Difference of binding-affinity for gefitinib between wild type EGFR and a mutant EGFR
Authors: Sojiro Kusumoto, Hiroo Ishida, Tomohide Sugiyama, Takamichi Hosaka, Koichi Ando, Masanao Nakashima, Toshimitsu Yamaoka, Kentaro Okuda, Tsukasa Ohnishi, Takashi Hirose, Naoya Horichi, Tsuyoki Kadofuku, Nagahiro Saijo, Mitsuru Adachi, Toshio Kuroki, Tohru Ohmori
Journal: Cancer Research (2007)

4562  Introduction: It was reported that mutations of EGFR such as 15 bp deletion in exon 19 or point mutation in exon 21 are frequently found in gefitinib-hypersensitive non small lung cancer patients. It is unknown how mutant EGFR acquire gefitinib hypersensitivity. It is assumed that mutant EGFR has a relation to its reactivity to ligand, downstream signal pathway, degradation or its own affinity for gefitinib. This time, to determine gefitinib hypersensitivity of mutant EGFR non small lung cancer, we examined EGFR binding affinity for gefitinib, using 15bp deletion mutant EGFR expressed cell lines.  Materials and Methods: To measure the affinity for the mutant EGFR,we used four cell lines PC-9, PC-14, 293_pΔ15 and 293_pEGFR . PC-9, a non small lung cancer cell line has mutant EGFR with 15 bp deletion in exon 19 endogenously, PC-14, another non small lung cancer cell line as control which expressed wild type EGFR. PC-9 cell line was approximately 1000 times hypersensitive to gefitinib (IC40=53.0 ± 8.1 nM) than PC-14 (IC40=47.0±9.1 µM). 293_pΔ15 and 293_pEGFR are stable transfected cell lines, that expressed the mutant EGFR with 15 bp deletion in exon 19 and wild type EGFR respectively. The cells were exposed varied concentrations of [14C] gefitinib and incubated 2 h at 4°C. After the incubation, cells were washed twice with ice cold PBS and processed for counting the radioactivity by liquid scintillation counter. To determine specific binding, nonspecific binding was measured in the presence of 200-fold molar excess of non-labeled gefitinib, and subtracted from total binding.  Results: Dissociation constants of gefitinib were at least 6.7-fold higher in wild type EGFR than that in 15 bp deletion mutant EGFR. Dissociation constants of gefitinib were well correlated with sensitivities to gefitinib.  Conclusion: There is a possibility that 15 bp deletion mutant EGFR may acquire hypersensitivity to gefitinib due to its high affinity for gefitinib.
Patient-reported quality of life (QOL) following CTL019 in pediatric and young adult patients (pts) with relapsed/refractory (r/r) b-cell acute lymphoblastic leukemia (B-ALL).
Authors: Andrew Charles Dietz, Stephan A. Grupp, Theodore Willis Laetsch, Heather Stefanski, Gary Douglas Myers, Henrique Bittencourt, Jochen Buechner, Eneida R. Nemecek, Paul L. Martin, Hidefumi Hiramatsu, Francoise Mechinaud, Gregory A. Yanik, Barbara De Moerloose, Patricia Ann Wood, Lawrence Rasouliyan, Yiyun Zhang, Simu K. Thomas, Sweta Shah, Andrew Harris
Journal: Journal of Clinical Oncology (2017)

10523 Background: The global ELIANA trial (NCT02435849) evaluates the efficacy and safety of CTL019, a single infusion of genetically modified autologous chimeric antigen receptor–expressing T cells targeting CD19+ cells in pediatric and young adult r/r B-ALL pts. Analyses show a complete response rate of 82% with or without complete blood count recovery ≤ 3 months. A serious adverse event rate of 71% was observed in ≤ 8 weeks of infusion, decreasing to 17% at &gt; 8 weeks (Grupp S, et al. Blood. 2016;128(22) [abstract 221].). This analysis further evaluates the clinical benefit of CTL019. QOL was assessed before and after CTL019 infusion. Methods: Infused pts were 3-23 y/o with CD19+ B-ALL who were chemo refractory, relapsed after allogeneic stem cell transplant (SCT), or otherwise ineligible for SCT. Pts ≥ 8 y completed the Pediatric Quality of Life Inventory (PedsQL) and EuroQol EQ-5D at baseline and following CTL019 infusion. Minimal clinically important differences are estimated to be 4.4 and 7 to 10 for PedsQL and EQ-5D, respectively. Results: 62 of 81 enrolled pts were infused; 56% had relapsed after SCT with median of 3 prior therapies. At interim analysis, 50 pts were treated ≥ 3 months prior to data cutoff and eligible for primary efficacy analysis. A total of 39 pts were ≥ 8 y. Mean PedsQL total and EQ-5D VAS scores, respectively, were 58.4 and 69.4 at baseline. Mean changes from baseline for the PedsQL total and EQ VAS scores, respectively, were 13.9 and 13.7 at month 3 and 12.8 and 10.9 at month 6, supporting clinically meaningful improvements in QOL. Similar trends were observed with each PedsQL subscale. With EQ-5D, the proportions of pts reporting problems with mobility, self-care, usual activities, anxiety/depression, or pain/discomfort were notably decreased at months 3 and 6 compared with baseline. Conclusions: Clinically meaningful improvements in QOL were observed at 3 and 6 months after CTL019 therapy in pediatric and young adult r/r B-ALL pts, including fewer problems in each EQ-5D domain. These results suggest improved QOL after this one-time immunocellular therapy beyond the period of acute toxicities. Clinical trial information: NCT02435849.
SAT0443 Identification of predictors of minimal disease activity in early psoriatic arthritis
Authors: A Zabotti, L Idolazzi, L Quartuccio, M Sartori, A Fassio, F Zuliani, D Gatti, M Rossini, S De Vita
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriatic arthritis (PsA) is a systemic inflammatory disease with articular and extra-articular features, the disease activity ranges from mild mono-oligoarthritis to destructive polyarthritis. Hence, establishing the prognosis of a patient with PsA is important to better define the treatment strategy. Furthermore, minimal disease activity (MDA) is a validated composite outcome measure since it correlates well with long-term outcomes (e.g. development of joint damage)<sup>1</sup>. <h3>Objectives</h3> The aim of this study was to identify the baseline clinical variables associated with MDA at 12th month of follow up in two cohorts of early PsA. <h3>Methods</h3> Consecutive PsA patients, attending the outpatient Early Arthritis Clinic in Udine or Verona in the last two years, were assessed. All the included patients had: I) CASPAR score ≥2<sup>2</sup> II) new diagnosis of PsA III) a complete clinical data and follow-up of at least 12 months. The GRAPPA recommendations on the management of PsA were followed. Statistical analysis included T- test, ANOVA and Pearson9s test in order to find possible predictors of MDA. <h3>Results</h3> Eighty-one early PsA patients were included in the study. 47/81 (58.2%) reached MDA at 12th month of follow-up; 68/81 (83.9%) were in c-DMARDs while 11/81 (13.6%) were in b-DMARDs. Two variables at baseline were selected comparing the groups based on achievement of MDA. These were: 1) LEI, which was significantly lower at baseline in patients reaching MDA (0.43 <i>Vs</i> 0.86, p=0.001); and 2) a lower baseline CRP (1.2 mg/dl <i>vs</i> 2.8 mg/dl, p=0.008). Of note, neither the baseline disease activity evaluated with DAPSA nor the time to referral were selected by statistical analysis. <h3>Conclusions</h3> Baseline lower LEI score and lower CRP were identified as clinical predictors of MDA after 12 months of treatment in PsA. Therefore, patients with a more active enthesitis or higher inflammation may have a less responsive disease. This may be relevant to select proper treatments at baseline, and indirectly confirms that enthesitis is a key therapeutic target in PsA. <h3>References</h3> Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis 2010; 69: 48–53. Coates LC, Conaghan PG, Emery P et al. Sensitivity and specificity of the classification of psoriatic arthritis criteria in early psoriatic arthritis. Arthritis Rheum 2012; 64: 3150–3155. <h3>Disclosure of Interest</h3> None declared
Unnecessary Staging Imaging in Early-Stage Breast Cancer
Authors: Heather R. Wolfe, Arjun Gupta, Navid Sadeghi
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations
Authors: Evan A. Stein, Eldad J. Dann, Albert Wiegman, Flemming Skovby, Daniel Gaudet, Etienne Sokal, Min-Ji Charng, Mafauzy Mohamed, Ilse Luirink, Joel S. Raichlen, Mattias Sundén, Stefan C. Carlsson, Frederick J. Raal, John J.P. Kastelein
Journal: Journal of the American College of Cardiology (2017)
FRI0066 Gastrin-releasing peptide and its receptor increase arthritis fibroblast-like synoviocyte invasiveness over the pi3k/akt pathway
Authors: M Farinon, VS Clarimundo, RT Pedό, VON Teixeira, C Nör, PS Gulko, RM Xavier, PG Oliveira
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease where the chronic inflammation and subsequent cartilage and bone erosion lead to joint destruction. The fibroblast-like synoviocytes (FLS) have a central role in disease pathogenesis and <i>in vitro</i> FLS invasiveness correlates with articular damage in RA patients. Gastrin-releasing peptide (GRP) plays an important role in the immune and inflammatory response. GRP is found in synovial fluid of RA patients and its receptor (GRPR) is found in synovial membrane of murine arthritis. RC-3095 in an antagonist of GRPR. <h3>Objectives</h3> To evaluate the role of GRP and GRPR on invasive behavior of mice FLS and to evaluate the GRP-induced signaling on PI3K/AKT pathway. <h3>Methods</h3> FLS were isolated from joints of DBA/1J mice with collagen-induced arthritis. Expression of GRPR in FLS was investigated by immunocytochemistry and western blot (WB). Proliferation of FLS treated with GRP (0.1 μM – 10 μM) (n=3) and RC-3095 (0.05 μM – 10 μM) (n=4) was assessed by Sulforhodamine B assay in 24h, 48h and 72h. Invasion assay with FLS was performed using a Matrigel-coated transwell system over 24h in two different experimental arms: first, FLS were treated with GRP (10 μM), RC-3095 (1 μM) or GRP+RC-3095 (GRP 10 μM and RC-3095 1 μM) (n=6) and after, FLS were treated with GRP (10 μM), Ly294002 (10 μM), or GRP+Ly294002 (GRP 10 μM and Ly294002 10 μM) (n=4). Akt phosphorylation was assessed by WB. <h3>Results</h3> GRPR protein was detected in FLS both by immunocytochemistry and WB. GRP and RC-3095 treatments did not affect FLS proliferation. Exposure to GRP increased FLS invasion (5356±1027) by nearly two-fold compared with untreated cells (2845±532) (p&lt;0.02), while the treatment with RC-3095 reduced FLS invasion (1723±271) compared with untreated cells. Treatment with GRP+RC-3095 (2670±499) reversed the invasiveness effect of GRP (p&lt;0.0001). GRP also increased phosphorylated AKT expression in FLS by 30% (p&lt;0.001). When Ly294002 was added with GRP (7772±1200), it prevented the GRP-induced increased cell invasiveness (11036±953.6) (p&lt;0.001) (Figure 1). <h3>Conclusions</h3> Our group demonstrated for the first time GRPR expression in FLS and that GRP are able to activate FLS invasion through AKT pathway. Finally, our results suggest that GRP/GRPR pathway could be relevant in the development of FLS-targeted therapy for RA. <h3>References</h3> Scott TL et al. Lancet 376;9746:1094–108. Bottini N, Firestein GS. Nat Rev Rheumatol 2013;9:24–33. Grimsholm O et al. Arthritis Res Ther 2005;7:R416–26. Oliveira PG et al. Arthritis Rheum 2011;63:2956–2965. <h3>Acknowledgements</h3> FIPE-HCPA, CAPES, CNPq. <h3>Disclosure of Interest</h3> None declared
Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease
Authors: Scott C. Neu, Judy Pa, Walter Kukull, Duane Beekly, Amanda Kuzma, Prabhakaran Gangadharan, Li-San Wang, Klaus Romero, Stephen P. Arneric, Alberto Redolfi, Daniele Orlandi, Giovanni B. Frisoni, Rhoda Au, Sherral Devine, Sanford Auerbach, Ana Espinosa, Mercè Boada, Agustín Ruiz, Sterling C. Johnson, Rebecca Koscik, Jiun-Jie Wang, Wen-Chuin Hsu, Yao-Liang Chen, Arthur W. Toga
Journal: JAMA Neurology (2017)

<h3>Importance</h3> It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established. <h3>Objective</h3> To determine how sex and APOE genotype affect the risks for developing MCI and AD. <h3>Data Sources</h3> Twenty-seven independent research studies in the Global Alzheimer's Association Interactive Network with data on nearly 58 000 participants. <h3>Study Selection</h3> Non-Hispanic white individuals with clinical diagnostic and APOE genotype data. <h3>Data Extraction and Synthesis</h3> Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. <h3>Main Outcomes and Measures</h3> Age-adjusted odds ratios (ORs) and 95% confidence intervals for developing MCI and AD were calculated for men and women across APOE genotypes. <h3>Results</h3> Participants were men and women between ages 55 and 85 years. Across data sets most participants were white, and for many participants, racial/ethnic information was either not collected or not known. Men (OR, 3.09; 95% CI, 2.79-3.42) and women (OR, 3.31; CI, 3.03-3.61) with the APOE ε3/ε4 genotype from ages 55 to 85 years did not show a difference in AD risk; however, women had an increased risk compared with men between the ages of 65 and 75 years (women, OR, 4.37; 95% CI, 3.82-5.00; men, OR, 3.14; 95% CI, 2.68-3.67;<i>P = </i>.002). Men with APOE ε3/ε4 had an increased risk of AD compared with men with APOE ε3/ε3. The APOE ε2/ε3 genotype conferred a protective effect on women (OR, 0.51; 95% CI, 0.43-0.61) decreasing their risk of AD more (<i>P</i>value = .01) than men (OR, 0.71; 95% CI, 0.60-0.85). There was no difference between men with APOE ε3/ε4 (OR, 1.55; 95% CI, 1.36-1.76) and women (OR, 1.60; 95% CI, 1.43-1.81) in their risk of developing MCI between the ages of 55 and 85 years, but women had an increased risk between 55 and 70 years (women, OR, 1.43; 95% CI, 1.19-1.73; men, OR, 1.07; 95% CI, 0.87-1.30;<i>P = </i>.05). There were no significant differences between men and women in their risks for converting from MCI to AD between the ages of 55 and 85 years. Individuals with APOE ε4/ε4 showed increased risks vs individuals with ε3/ε4, but no significant differences between men and women with ε4/ε4 were seen. <h3>Conclusions and Relevance</h3> Contrary to long-standing views, men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.
骨組織工学のための電気紡糸したコラーゲン足場のバイオインスパイアードin situ架橋と鉱化作用【Powered by NICT】
Authors: Dhand Chetna, Ong Seow Theng, Dwivedi Neeraj, Diaz Silvia Marrero, Venugopal Jayarama Reddy, Navaneethan Balchandar, Fazil Mobashar H.U.T., Liu Shouping, Seitz Vera, Wintermantel Erich, W Beuerman Roger, Ramakrishna Seeram, K Verma Navin, Lakshminarayanan Rajamani
Journal: Biomaterials (2016)
Balanced Adoption of Radial Artery Access for Primary Percutaneous Coronary Intervention
Authors: H. Vernon Anderson, David P. Faxon
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy
Authors: Nicola M. Tomas, Catherine Meyer-Schwesinger, Hanning von Spiegel, Ahmed M. Kotb, Gunther Zahner, Elion Hoxha, Udo Helmchen, Nicole Endlich, Friedrich Koch-Nolte, Rolf A.K. Stahl
Journal: Journal of the American Society of Nephrology (2017)

Thrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia. Immunofluorescence analyses revealed granular antigen-antibody complexes in a subepithelial location along the glomerular filtration barrier 14 days after antibody injection, and immunohistochemistry for rabbit IgG and THSD7A as well as ultrastructural analyses showed the typical characteristics of human MN. Mice injected with purified IgG from rabbit serum that was taken before immunization failed to develop any of these changes. Notably, MN developed in the absence of detectable complement activation, and disease was strain dependent. In vitro , anti-THSD7A antibodies caused cytoskeletal rearrangement and activation of focal adhesion signaling. Knockdown of the THSD7A ortholog, thsd7aa, in zebrafish larvae resulted in altered podocyte differentiation and impaired glomerular filtration barrier function, with development of pericardial edema, suggesting an important role of THSD7A in glomerular filtration barrier integrity. In summary, our study introduces a heterologous mouse model that allows further investigation of the molecular events that underlie MN.
Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial
Authors: Hagop M Kantarjian, Gail J Roboz, Patricia L Kropf, Karen W L Yee, Casey L O'Connell, Raoul Tibes, Katherine J Walsh, Nikolai A Podoltsev, Elizabeth A Griffiths, Elias Jabbour, Guillermo Garcia-Manero, David Rizzieri, Wendy Stock, Michael R Savona, Todd L Rosenblat, Jesus G Berdeja, Farhad Ravandi, Edwin P Rock, Yong Hao, Mohammad Azab, Jean-Pierre J Issa
Journal: The Lancet Oncology (2017)