tbuckley/cabot-search huggingface dataset:
Preclinical Evaluation of Intravesical Cisplatin Nanoparticles for Non–Muscle-Invasive Bladder Cancer
Authors: Max Kates, Abhijit Date, Takahiro Yoshida, Umara Afzal, Pranjali Kanvinde, Taarika Babu, Nikolai A. Sopko, Hotaka Matsui, Noah M. Hahn, David J. McConkey, Alexander Baras, Justin Hanes, Laura Ensign, Trinity J. Bivalacqua
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Prior clinical trials evaluating cisplatin for non–muscle-invasive bladder cancer (NMIBC) were stopped due to local and systemic toxicity. Currently, there is still a need for improved intravesical therapies, and nanoparticle-based CDDP may be efficacious without the toxicity of free cisplatin observed in the past. Experimental Design: Cisplatin nanoparticles (CDDP NPs) were developed using biocompatible poly(l-aspartic acid sodium salt; PAA), both with and without low and high grafting density of methoxy-polyethylene glycol (PEG). In vitro cytotoxicity studies confirmed activity of CDDP NPs and CDDP solution against a papillary bladder cancer cell line. Local toxicity was assessed by three weekly intravesical administrations of CDDP formulations. CDDP NPs and CDDP solution were evaluated for bladder absorption in murine models 1 and 4 hours after intravesical administration. In vivo efficacy was evaluated in an immunocompetent carcinogen model of NMIBC. Results: CDDP NPs showed decreased local toxicity, as assessed by bladder weight, compared with CDDP solution. Furthermore, &amp;gt;2 μg/mL of platinum was observed in mouse serum after intravesical administration of CDDP solution, whereas serum platinum was below the limit of quantification after intravesical administration of CDDP NPs. CDDP NPs provided significantly increased (P &amp;lt; 0.05) drug levels in murine bladders compared with CDDP solution for at least 4 hours after intravesical administration. In vivo, CDDP NPs reduced cancer cell proliferation compared with untreated controls, and was the only treatment group without evidence of invasive carcinoma. Conclusions: Cisplatin-loaded PAA NPs have the potential to improve intravesical treatment of NMIBC while reducing local and systemic side effects. Clin Cancer Res; 23(21); 6592–601. ©2017 AACR.
False-Positive Ventilation-Perfusion Studies Due to Nonembolic Pulmonary Artery Compromise
Authors: Jonathan Alis, Miriam Hulkower, Anna Shmukler, Kwang J. Chun, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2017)

Abstract Ventilation/perfusion (V/Q) scans are highly sensitive in detecting clinically significant pulmonary embolisms; however, V/Q mismatches are not specific to pulmonary embolism alone, and other etiologies can cause false-positive results. We present 3 cases where the pulmonary vasculature was compromised, from either intraluminal narrowing or external compression, with resultant mismatches. This raises the importance of interpreting V/Q scan results in conjunction with a thorough medical/surgical history and careful analysis of the chest radiograph.
Abstract 106: A Novel Small Molecule Protects Against Myocardial Ischemia and Doxorubicin-Induced Cardiomyopathy Through Heat Shock Response and Proteostasis Regulation In Vivo
Authors: Sudhish Sharma, Savitha Deshmukh, Manuela Zampino, Brandon Walker, Sunjay Kaushal
Journal: Circulation Research (2012)

Background: A potentially new non-cell-based therapy is the systemic delivery of small molecules to revive or protect injured myocardium. By screening a drug library, we identified a novel small molecule, sk421, and tested its effectiveness in two myocardial injury models in vivo: a myocardial infarction model and doxorubicin (DOX)-induced cardiomyopathy model. Results: Sk421 significantly increased cellular viability of DOX-injured cardiomyocytes by preventing apoptosis in vitro, demonstrated by assays for MTT (p=0.042), annexin-V, and active caspase-3 (p=0.004). Sk421 increased the concentrations of the GATA4 and the heat shock proteins (HSPs) in cardiomyocytes (by 1.5-fold), and fibroblasts (by 1.2-fold), but was unable to rescue DOX-injured fibroblast cells depleted of HSPs. Sk421 maintained the total proteosome by a 3.5-fold inhibition of ubiquitinized GATA4 degradation, as shown by immunoprecipitation assays. Oral administration of sk421(4mg/kg) rescued DOX-injured mice by significantly preserving cardiac function, weight gain, cardiomyocyte lesion size and abundance, and by reducing overall mortality (20% in treated groups) compared to control DOX-injured mice (80% in untreated groups, p&lt;0.03). The levels of GATA4 and HSPs were increased in the sk421-rescued mice. In the MI model, (n=5/group), sk421 reduced myocardial infarct size, and protected heart function evaluated by ejection fraction 45.8 ± 2.4 vs. 34.8 ± 3.3, p=0.005 (day7), and 44.3 ± 2.8 vs. 34.4 ± 4.1, p=0.011 (day28). Sk421 treatment of MI rats resulted in a higher fraction of viable tissue (within the LV (70.20 ± 0.5024, n=3) as compared to only MI group (56.38 ± 3.879%, n=3) and the infiltration of CD68+ cells was found to be more in the infarct region of LV of MI group rats as compared to MI+CEL. Quantitative analysis showed a significantly higher proportion of TUNEL positive cells and mRNA levels of IL-1β, IL-6, TNF-α and MMP2 in the myocardium of MI rats compared to MI+SK421 rats. Conclusion: This study demonstrates the broad therapeutic benefit of sk421 in animal model of myocardial injury by mechanism of inducing the heat shock response and preserving GATA levels. The ease of oral delivery makes sk421 a potentially clinically useful adjunct for myocardial preservation.
SAT0149 Comparative effectiveness of tofacitinib, biologic drugs and traditional disease-modifying antirheumatic drugs in rheumatoid arthritis
Authors: CS Moura, MA Machado, H Behlouli, JR Curtis, M Abrahamowicz, S Bernatsky
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Most rheumatoid arthritis (RA) patients initiate therapy with methotrexate (MTX), but only 1/3 will have low disease activity with this agent alone. Several therapeutic options are available for patients with MTX-resistant RA, including new Janus kinase (JAK) inhibitors (eg.: tofacitinib). <h3>Objectives</h3> To compare the effectiveness of traditional disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs and tofacitinib for RA patients with inadequate response to MTX. <h3>Methods</h3> We used MarketScan® databases (2011–2014) to study adult RA individuals previously treated with methotrexate (oral or SQ) and newly prescribed one of the medications under study. The date of first filled prescription or infusion drug was defined as the cohort entry and a 12-month pre-period was used to exclude prior users of biologics or tofacitinib. We required subjects to be continuously enrolled in the medical and pharmacy plan 12 months before and after the cohort entry. Effectiveness was access through an algorithm previously validated<sup>1</sup>, based on the following criteria: 1) non-adherence; 2) switching/adding a new biologic or tofacitinib; 3) switching/adding a new DMARD; 4) increasing of the dose of the starting therapy; 5) use of glucocorticoid joint injections; and 6) increasing the dose of oral glucocorticoid. A patient9s therapy was defined as not effective if at least one of the criterion occurred during the first year of follow-up. <h3>Results</h3> 16,305 RA patients were included; 2,879 began therapy with DMARD, 13,345 with biologics and 81 with tofacitinib. Among all patients, 77.5% were female and the mean age was 56.2 years (standard deviation 12.6). Table 1 shows the proportion of patients that meet the individual criterion and that achieved effectiveness at the end of one-year follow-up. <h3>Conclusions</h3> Similar rates of therapy effectiveness were observed among groups, although the rates for the individual criteria differed. Fewer patients initiating biologic agents were non-adherent compared to DMARD and tofacitinib therapy, but switch/adding and injections tended to be higher in this group. <h3>References</h3> Curtis JR et al. Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis. Arthritis Res Ther. 2011;13(5). <h3>Disclosure of Interest</h3> None declared
Ex Vivo High-Throughput Flow Cytometry Screening Identifies Subsets of Responders to Differentiation Agents in Individual AML Patient Samples
Authors: Sacha L. Prashad, Leylah Drusbosky, Hassan Sibai, Mark D. Minden, Stephen J. Western, Chris Biondi, Reecha Shah, Debra Liu, Transon Nguyen, Connor Warnock, Pete Quinzio, Matthew De Silva, Elie Traer, Christopher R. Cogle, Aaron D. Schimmer, Diane Heiser
Journal: Blood (2016)
プラズモン同調可能なRaman/FTIRイメージングによる効率的なin vitroおよびin vivoでの実時間SERS検出とドラッグデリバリーのための金ナノスター【Powered by NICT】
Authors: Tian Furong, Conde Joao, Bao Chenchen, Chen Yunsheng, Curtin James, Cui Daxiang
Journal: Biomaterials (2016)
Indolent Phenotype of RAS-Associated Autoimmune Leukoproliferative Disorder (RALD) Is Characterized By Single Somatic Mutations in RAS Genes with Absence of Cooperating Mutations
Authors: Vollter Anastas, Weixin Wang, Susan Price, Zhen Zhao, V. Koneti Rao, Katherine R. Calvo
Journal: Blood (2016)
Defective Cyclin B1 Induction in Trastuzumab-emtansine (T-DM1) Acquired Resistance in HER2-positive Breast Cancer
Authors: MohammadA Sabbaghi, Gabriel Gil-Gómez, Cristina Guardia, Sonia Servitja, Oriol Arpí, Sara García-Alonso, Silvia Menendez, Montserrat Arumi-Uria, Laia Serrano, Marta Salido, Aura Muntasell, Maria Martínez-García, Sandra Zazo, Cristina Chamizo, Paula González-Alonso, Juan Madoz-Gúrpide, Pilar Eroles, Joaquin Arribas, Ignasi Tusquets, Ana Lluch, Atanasio Pandiella, Federico Rojo, Ana Rovira, Joan Albanell
Journal: Clinical Cancer Research (2017)

Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2-positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance.Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3, and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions. Genetic modifications to up- or downregulate cyclin B1 were conducted. Effects of T-DM1 on cyclin B1 levels, proliferation, and apoptosis were assayed in human HER2-positive breast cancer explants.Results: We obtained three cell lines with different levels of acquired T-DM1 resistance (HCC1954/TDR, HCC1419/TDR, and SKBR3/TDR cells). HER2 remained amplified in the resistant cells. Binding to HER2 and intracellular uptake of T-DM1 were maintained in resistant cells. T-DM1 induced cyclin B1 accumulation in sensitive but not resistant cells. Cyclin B1 knockdown by siRNA in parental cells induced T-DM1 resistance, while increased levels of cyclin B1 by silencing cdc20 partially sensitized resistant cells. In a series of 18 HER2-positive breast cancer fresh explants, T-DM1 effects on proliferation and apoptosis paralleled cyclin B1 accumulation.Conclusions: Defective cyclin B1 induction by T-DM1 mediates acquired resistance in HER2-positive breast cancer cells. These results support the testing of cyclin B1 induction upon T-DM1 treatment as a pharmacodynamic predictor in HER2-positive breast cancer. Clin Cancer Res; 23(22); 7006-19. ©2017 AACR.
Review of Epidemiological Studies of Drinking-Water Turbidity in Relation to Acute Gastrointestinal Illness
Authors: Anneclaire J. De Roos, Patrick L. Gurian, Lucy F. Robinson, Arjita Rai, Issa Zakeri, Michelle C. Kondo
Journal: Environmental Health Perspectives (2017)

Turbidity has been used as an indicator of microbiological contamination of drinking water in time-series studies attempting to discern the presence of waterborne gastrointestinal illness; however, the utility of turbidity as a proxy exposure measure has been questioned.We conducted a review of epidemiological studies of the association between turbidity of drinking-water supplies and incidence of acute gastrointestinal illness (AGI), including a synthesis of the overall weight of evidence. Our goal was to evaluate the potential for causal inference from the studies.We identified 14 studies on the topic (distinct by region, time period and/or population). We evaluated each study with regard to modeling approaches, potential biases, and the strength of evidence. We also considered consistencies and differences in the collective results.Positive associations between drinking-water turbidity and AGI incidence were found in different cities and time periods, and with both unfiltered and filtered supplies. There was some evidence for a stronger association at higher turbidity levels. The studies appeared to adequately adjust for confounding. There was fair consistency in the notable lags between turbidity measurement and AGI identification, which fell between 6 and 10 d in many studies.The observed associations suggest a detectable incidence of waterborne AGI from drinking water in the systems and time periods studied. However, some discrepant results indicate that the association may be context specific. Combining turbidity with seasonal and climatic factors, additional water quality measures, and treatment data may enhance predictive modeling in future studies. https://doi.org/10.1289/EHP1090.
低酸素指向と活性化セラノスティック剤:固形腫瘍の画像診断と治療【Powered by NICT】
Authors: Kumar Rajesh, Kim Eun-Joong, Han Jiyou, Lee Hyunseung, Shin Weon Sup, Kim Hyun Min, Bhuniya Sankarprasad, Kim Jong Seung, Hong Kwan Soo
Journal: Biomaterials (2016)
Persistence of Poliovirus Neutralizing Antibodies Eight Years after Immunization with Live, Attenuated-Virus Vaccine
Authors: Wyatt E. Rousseau, Gary R. Noble, Gary E. Tegtmeier, M. Colin Jordan, Tom D. Y. Chin
Journal: New England Journal of Medicine (1973)

IN 1964 this laboratory studied the booster effect of two doses of trivalent oral poliovirus vaccine in children previously immunized with formalin-inactivated vaccine. Five weeks after the second dose of the trivalent vaccine 97, 100 and 98 per cent of 200 children studied had detectable antibodies (serum titer ≥ 1:4) to poliovirus Types 1, 2 and 3, respectively.1 , 2 In 1968 a second study was made of the population, which then consisted of 99 children, and the proportions with detectable antibodies to the three poliovirus types were 97, 100 and 88 per cent, respectively.2 Other studies3 4 5 have noted similar decreases in . . .
Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis
Authors: Javier Fernández, Juan Acevedo, Reiner Wiest, Thierry Gustot, Alex Amoros, Carme Deulofeu, Enric Reverter, Javier Martínez, Faouzi Saliba, Rajiv Jalan, Tania Welzel, Marco Pavesi, María Hernández-Tejero, Pere Ginès, Vicente Arroyo
Journal: Gut (2017)

Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk of infection. This investigation evaluated prevalence and characteristics of bacterial and fungal infections causing and complicating ACLF, predictors of follow-up bacterial infections and impact of bacterial infections on survival. Patients 407 patients with ACLF and 235 patients with acute decompensation (AD). Results 152 patients (37%) presented bacterial infections at ACLF diagnosis; 46%(n=117) of the remaining 255 patients with ACLF developed bacterial infections during follow-up (4 weeks). The corresponding figures in patients with AD were 25% and 18% (p&lt;0.001). Severe infections (spontaneous bacterial peritonitis, pneumonia, severe sepsis/shock, nosocomial infections and infections caused by multiresistant organisms) were more prevalent in patients with ACLF. Patients with ACLF and bacterial infections (either at diagnosis or during follow-up) showed higher grade of systemic inflammation at diagnosis of the syndrome, worse clinical course (ACLF 2-3 at final assessment: 47% vs 26%; p&lt;0.001) and lower 90-day probability of survival (49% vs 72.5%;p&lt;0.001) than patients with ACLF without infection. Bacterial infections were independently associated with mortality in patients with ACLF-1 and ACLF-2. Fungal infections developed in 9 patients with ACLF (2%) and in none with AD, occurred mainly after ACLF diagnosis (78%) and had high 90-day mortality (71%). Conclusion Bacterial infections are extremely frequent in ACLF. They are severe and associated with intense systemic inflammation, poor clinical course and high mortality. Patients with ACLF are highly predisposed to develop bacterial infections within a short follow-up period and could benefit from prophylactic strategies.
Abstract 12678: Clinical Utility of Echocardiographic Epicardial Adipose Tissue Thickness Measured Using a High-frequency Linear Probe in Patients With Coronary Artery Disease
Authors: Yukia Hirata, Hirotsugu Yamada, Kenya Kusunose, Susumu Nishio, Mika Bando, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2015)

Introduction: Epicardial adipose tissue(EAT), which is thought to be an ectopic adipose tissue, has been paid attention in association with coronary artery disease (CAD). Hypothesis: We hypothesized that EAT in anterior interventricular groove (AIG) obtained by echocardiography can be an additional marker over classical risk factors for prediction of CAD. Methods: We enrolled 311 patients (mean age 67±11 yrs, 208 men) who underwent coronary angiography between December 2011 and December 2013 at our hospital. We measured EAT thickness on the AIG and right ventricular free wall (EAT-RV) using high-frequency linear probe. Subjects were divided into 2 groups with and without significant coronary stenosis (≧75%) from coronary angiography. The performance of clinical risk factors (including age, male gender, body mass index (BMI), diabetes mellitus, hypertension, dyslipidemia, and smoking) plus various combinations of EAT thickness measurements for predicting CAD was assessed using the area under the curve (AUC) in ROC analysis. Results: The EAT-AIG thickness was significantly greater in the CAD group than that in the non-CAD group (8.3±3.0 vs. 6.3±2.5 mm, p&lt;0.001), and there as also significant difference in the EAT-RV between the two groups (5.0±2.1 vs. 4.4±2.3 mm, p=0.009). Adding the EAT-AIG thickness over classical risk factors improved prediction of presence CAD (AUC 0.692 vs. 0.788, p&lt;0.001), while the EAT-RV did not (AUC 0.692 vs. 0.704, p=0.343). Conclusions: Echocardiographic EAT-AIG thickness was greater in the CAD group than the non-CAD group. This non-invasive index may have clinical potential as a maker for predicting coronary atherosclerosis.
転移性結腸直腸癌(MCRC)患者におけるパニツムマブ+FOLFIRIの一次療法研究(20060314)の患者‐報告成績(PRO)
Authors: Karthaus M, Resch G, Mineur L, Hofheinz R, Greil R, Letocha H, Fernebro E, Gamelin E, Decosta L, Koehne C
Journal: Annals of Oncology (2010)
New Leukemia, Lymphoma Diagnostic
Authors: Rebecca Voelker
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
Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean
Authors: Chao Fang, Yanming Ma, Shiwen Wu, Zhi Liu, Zheng Wang, Rui Yang, Guanghui Hu, Zhengkui Zhou, Hong Yu, Min Zhang, Yi Pan, Guoan Zhou, Haixiang Ren, Weiguang Du, Hongrui Yan, Yanping Wang, Dezhi Han, Yanting Shen, Shulin Liu, Tengfei Liu, Jixiang Zhang, Hao Qin, Jia Yuan, Xiaohui Yuan, Fanjiang Kong, Baohui Liu, Jiayang Li, Zhiwu Zhang, Guodong Wang, Baoge Zhu, Zhixi Tian
Journal: Genome biology (2017)

Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.
Rescue of T-cell function during persistent pulmonary adenoviral infection by Toll-like receptor 9 activation
Authors: Tristan Holland, Dirk Wohlleber, Samira Marx, Thomas Kreutzberg, Salvador Vento-Asturias, Christine Schmitt-Mbamunyo, Meike Welz, Marianne Janas, Karl Komander, Sarah Eickhoff, Anna Brewitz, Mike Hasenberg, Linda Männ, Matthias Gunzer, Christoph Wilhelm, Wolfgang Kastenmüller, Percy Knolle, Zeinab Abdullah, Christian Kurts, Natalio Garbi
Journal: Journal of Allergy and Clinical Immunology (2017)
Respiratory Muscle Weakness Elicits Inefficient Ventilation Resulting in the Deterioration of Exercise Intolerance in Patients with Chronic Heart Failure
Authors: Hamazaki Nobuaki, Masuda Takashi, Kamiya Kentaro, Matsuzawa Ryota, Nozaki Kohei, Tanaka Shinya, Akiyama Ayako, Aoyama Akihiro, Yabu Kanae, Nakamura Takeshi, Maekawa Emi, Noda Chiharu, Yamaoka-Tojoh Minako, Ako Junya
Journal: Circulation (2016)
Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression
Authors: Yu Zhu, John M. Herndon, Dorothy K. Sojka, Ki-Wook Kim, Brett L. Knolhoff, Chong Zuo, Darren R. Cullinan, Jingqin Luo, Audrey R. Bearden, Kory J. Lavine, Wayne M. Yokoyama, William G. Hawkins, Ryan C. Fields, Gwendalyn J. Randolph, David G. DeNardo
Journal: Immunity (2017)