tbuckley/cabot-search huggingface dataset:
Abstract 4110: Measurement of autophagy in sensitive versus resistant breast cancer cells
Authors: Ayesha N. Shajahan, Rory Olson, Mathew Webb, Jennifer Samoy, John Zielinski, Michael Mullenix, Robert Clarke
Journal: Cancer Research (2012)

Abstract In 2011, there will be almost 192,000 newly diagnosed cases of invasive breast cancer in the U.S. with estrogen receptor positive ≤ positive (ER+) tumors. For these patients, endocrine therapy, administered as an antiestrogen, e.g., Tamoxifen (TAM) or Faslodex (Fulvestrant; ICI 182,780) or an aromatase inhibitor (AI), is the least toxic and most effective means to manage their hormone-dependent breast cancer. Tamoxifen (TAM) produces a 26% proportional reduction in mortality, however, advanced ER+ breast cancer largely remains an incurable disease and resistance to endocrine therapy remains a significant clinical problem. We and others have shown that antiestrogen resistant breast cancer cells have higher level of basal autophagy, a process that allows the cells to survive stress by digesting its own organelles. However, the precise role of this sustained autophagy in antiestrogen resistance is unclear and the measurement of autophagy flux, the dynamic measurement of passage of substrates through the autophagic pathway, is essential to determine levels of autophagy in a cell. In this study, we investigate the rate of autophagosome formation and degradation in antiestrogen sensitive versus antiestrogen resistant breast cancer cells. Autophagosome formation was measured using autophagosome specific fluorescent dye incorporation (Cyto-IDTM). Progression of autophagy was indicated by the degradation SQSTM1/p62 and NBR1 in cell lysates as measured by colorimentric enzyme immunoassays (ELISAs). The ELISAs were validated to provide biologically relevant sensitivity, dilutional linearity, reproducibility and recovery in native samples. Cells further progressing into apoptosis and cell death were identified by fluorescence using a combination of yellow emitting dye labeled Annexin V and a red emitting viability dye (GFP-Certified™Apoptosis/Necrosis detection kit). We hypothesize that combination of sustained autophagosome formation and inhibition of degradation are crucial in promoting pro-survival autophagy in antiestrogen resistant breast cancer cells. We show that while autophagosome formation and concurrent degradation of SQSTM1/p62 and NBR1 leads to cell death in sensitive cells, resistant cells have higher levels of autophagosomes, lower levels of degradation of SQSTM1/p62 and NBR1 and decreased cell death. Our data will highlight the importance of determining autophagy flux in pro-death versus pro-survival autophagy in drug resistance in breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4110. doi:1538-7445.AM2012-4110
Interview with Alain Enthoven: is there convergence between Britain and the United States in the organisation of health services?
Authors: P. Newman
Journal: BMJ (1995)

InternetThe internet has recently received a lot of publicity because the number ofpeople connected to the system is growing rapidly.In addition to offering instantaneous email facilities, it is possible to link up with thousands of other computers on the system to get access to news, information, photographs, sound, or video on virtually any subject that you can imagine.Like it or not, computers are becoming increasingly integrated into our professional lives.Computers give us the ability to do tasks that were only dreamt ofjust a few decades ago and mastering them can help us to do our work faster and more efficiently.
Phase II study of denileukin diftitox with CHOP chemotherapy in newly-diagnosed PTCL: CONCEPT trial.
Authors: F. M. Foss, N. N. Sjak-Shie, A. Goy, R. Advani, E. D. Jacobsen
Journal: Journal of Clinical Oncology (2010)

8045 Background: Denileukin diftitox (DD), a genetically engineered fusion protein, targets malignancies expressing the IL-2 receptor and has demonstrated a 48% objective response rate in relapsed/refractory PTCL. Because DD is not myelosuppressive and induces apoptosis by inhibition of protein synthesis, a mechanism of action non-cross-resistant with chemotherapy, we evaluated the efficacy and safety of the combination of CHOP with DD in newly diagnosed aggressive T-cell lymphomas. Methods: In this multicenter Phase II study, pts with aggressive T-NHL according to WHO classification were eligible. Pts with mycosis fungoides or the Sezary syndrome were excluded. Therapy was Dd at 18 mcg/kg/day on Days 1 and 2, CHOP on Day 3, and G-CSF or filgrastim Day 4. Cycles were every 3 weeks × 6 . Restaging studies were performed after every 2 cycles Results: 49 pts were enrolled. The median age was 52 (range 22-80). Histopathologic subtypes included: ALCL 8, AILT 10, PTCLnos 19, ITCL 3, panniculitis-like TCL (sPTCL) 5, NK/T 1, hepatosplenic TCL 1. ECOG PS was 1 in 63%, and 36% had B-symptoms. The median cycles was 6 with 7 pts completing only 1 cycle of therapy; 3 pts died after cycle 1 ( 2 cardiac, 1 rhabdomyolysis) and 4 were taken off study for toxicity. The ORR in 49 pts was 65% with 51% CR. In the efficacy-evaluable pts (≥2 cycles) the ORR was 86% (CR 73%). Response rates in subgroups were: PTCLnos 47%; AITL 80%; ALCL 87%; ITCL 33%; sPTCL 60%. Median PFS for the 49 pts was 12 mo and 2-year estimated OS was 60%. Median response duration for 32 responders was 29 mo. The most frequent grade 3/4 AEs (>5%) were leucopenia (20%), thrombocytopenia (12%), and febrile neutropenia (12%). DD- associated toxicities included infusion related rigor in 7 pts, hypoalbuminemia in 17, and acute hypersensitivity in 1. Conclusions: The combination of DD and CHOP appears to be clinically active with 68% ORR and 57% CR in PTCL and was generally well tolerated. Based on these encouraging results, a multi-center randomized trial comparing CHOP to DD with CHOP is being initiated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai
Community acquired MRSA infections in a paediatric population in Greece
Authors: S Vourli, D Perimeni, A Makri, M Polemis, A Voyiatzi, A Vatopoulos
Journal: Eurosurveillance (2005)

We investigated the characteristics of 20 community acquired methicillin resistant Staphylococcus aureus (MRSA) strains isolated in a paediatric hospital in Athens. Eighteen of these, all isolated from skin and soft tissue infections, carried the Panton-Valentine leukocidin (PVL) determinants. They all were found resistant to fusidic acid, tetracycline and kanamycin, and displayed a PFGE pattern identical to that of the well-described ST80 CA-MRSA clone circulating in various European countries.
AB1113 Pressure pain threshold and pain coping strategies in juvenile idiopathic arthritis: A cross-sectional study
Authors: A. Leegaard, J.H. Jeppesen, M. Thastum, T. Herlin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pain is a primary symptom in juvenile idiopathic arthritis (JIA), and we have previously shown that children with JIA have a decreased pain threshold when compared with healthy age-related children. The reason for this, however, remains uncertain. Biological as well as psychological factors may be influential. The association between pain and coping strategies is well known and well documented. It is important to clarify the effect of coping strategies on pain threshold among children with JIA in order to better target pain treatment of these children. <h3>Objectives</h3> To assess the pressure pain threshold and pain coping strategies of children with JIA compared with a healthy control group. We also aim to assess any association between pressure pain threshold and pain coping strategies among children with JIA. <h3>Methods</h3> We included 58 children with JIA born 1995 to 2000 admitted to the pediatric rheumatology clinic. Ninety-one age-related healthy school children served as a control group. All children were asked to complete a subscale of the Pain Coping Questionnaire. Afterwards, pain threshold was measured using a digital pressure algometer on 17 symmetric, anatomically predefined joint or bone-related points. <h3>Results</h3> Children with JIA were less likely to use positive self-statements (t: -2.85, p=0.005, Cohen's d = -0.48) as well as cognitive and behavioral distraction (t: -3.81, p&lt;0.001, Cohen's d = -0.63, and t: -2.71, p=0.008, Cohen's d = -0.46, respectively). They used significantly more internalizing/catastrophizing coping strategies when compared with children in the healthy control group (t: 2.22, p=0.028, Cohen's d =0.38). However, we found no correlation between pain threshold and any of the pain coping strategies among the children with JIA (p=0.138-0.608, <i>r</i> =0.07-0.20). The pain threshold was significantly lower among children with JIA (total mean PT =1.33±0.69 kg/cm<sup>2</sup>) when compared with the healthy control group (total mean PT =1.77±0.67 kg/cm<sup>2</sup>). The same pattern was found in all areas measured (p&lt;0.001-0.005). <h3>Conclusions</h3> Although children with JIA seem to differ from healthy children with regard to their pressure pain threshold as well as to their pain coping strategies, the lack of association between the two outcomes suggests that the enhanced use of mal-adaptive pain coping strategies cannot explain the decreased pressure pain threshold of children with JIA in our study. Other factors such as sensitization may be influential, but further studies in this area are needed. <h3>Disclosure of Interest</h3> None Declared
Focal Cerebral Hypermetabolism Due to Nonconvulsive Status Epilepticus Mimicking Metastasis in Staging a Patient With Lung Cancer by FDG PET/CT
Authors: Szu-Kuan Yang, Yu-Lin Pei, Chia-Hung Kao, Jainn-Shiun Chiu, Guang-Uei Hung
Journal: Clinical Nuclear Medicine (2011)

Here we report a case of a 77-year-old man referred for staging his lung cancer by FDG PET/CT. In addition to the primary lung cancer, focal hypermetabolism was noted in right hemisphere of brain, which was initially considered as metastasis. However, there was no significantly morphologic abnormality on the coregistered CT image. Further MRI study revealed no evidence of tumor, metastasis, inflammation/infection, or infarction over the corresponding regions. The associated symptoms/signs included left limb weakness, mental confusion, and occasional right facial twitching. Electroencephalography revealed typical findings of active epilepsy. A nonconvulsive status epilepticus originating at right centroparietal area was finally concluded.
F-18 FDG PET/CT Findings in Two Patients With Pyothorax-Associated Lymphoma
Authors: Kimiteru Ito, Kazuo Kubota, Miyako Morooka, Takashi Aruga, Nozomu Mochizuki, Jun Itami, Hiroshi Matsuda
Journal: Clinical Nuclear Medicine (2010)

We report 2 cases of pyothorax-associated lymphoma that underwent F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) examinations during pre- and post-treatment states. The FDG PET/CT examinations were able to define the massive lesions as areas of intensive FDG uptake. After radiotherapy, follow-up PET/CT examinations showed the disappearance of the abnormal FDG uptake, although the residual masses remained in the original regions. Finally, we concluded that these lesions had entered remission based on the PET/CT findings. These cases indicate that PET/CT is a useful modality for detecting pyothorax-associated lymphoma and for evaluating the efficacy of treatments.
Molecular analysis of the CALM/AF10 fusion: identical rearrangements in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma patients
Authors: SK Bohlander, V Muschinsky, K Schrader, R Siebert, B Schlegelberger, L Harder, V Schemmel, C Fonatsch, W-D Ludwig, W Hiddemann, MH Dreyling
Journal: Leukemia (2000)
Garenoxacin Prophylaxis for Febrile Neutropenia After Chemotherapy in Hematological Malignancies
Authors: N. Nakamura, H. Tsurumi, Y. Shibata, R. Mabuchi, J. Kitagawa, A. Suetsugu, N. Kanemura, N. Goto, T. Hara, H. Moriwaki
Journal: Annals of Oncology (2013)
DRENAJE DE COLECCIONES PANCREÁTICAS GUIADO POR USE MEDIANTE NUEVA PRÓTESIS METÁLICA DE APROXIMACIÓN LUMINAL-AXIOS
Authors: JB Gornals, C de La Serna-Higuera, A Sánchez-Yague, C Loras, AM Sánchez-Cantos, JC Espinós, A González-Canoniga, M Varas, M Pérez-Miranda
Journal: Endoscopy (2011)

Introducción: el drenaje de colecciones pancreáticas mediante prótesis metálicas ofrece un mayor diámetro que las plásticas y permite la quistoscopia, pero su diseño tubular favorece la migración.
TCTAP A-148 Comparison of Predictors of Stent Thrombosis Between 1st Generation and 2nd Generation Drug-Eluting Stents Deployment in Patients with Acute Myocardial Infarction
Authors: Jong Yop Pae, Seung-Ho Hur, Chang-Wook Nam, Hyuck Jun Yoon, Yun-Kyeong Cho, Kwon-Bae Kim
Journal: Journal of the American College of Cardiology (2015)
Endoscopic retrograde cholangiopancreatography
Authors: T. Baron
Journal: Endoscopy (2010)

The 2010 Digestive Disease Week (DDW; 1 – 5 May, New Orleans, Louisiana, USA) showed that advances in endoscopic retrograde cholangiopancreatography (ERCP) continue to be made, though perhaps at a relatively slower rate than a decade ago. Nonetheless, important data on topics including biliary cannulation, the use of expandable metal stents for benign disease, and biliary cellular imaging were presented at the conference and key abstracts are discussed here.
FRI0426 High Prevalence of Overweight and Obesity in Recently Diagnosed Systemic Lupus Erythematosus Patients in an International Registry: Table 1.
Authors: M. Zen, B. Parker, M.B. Urowitz, I.N. Bruce
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To examine the prevalence of overweight and obesity in a cross-sectional cohort of early SLE patients and to determine factors associated with overweight in this population. <h3>Methods</h3> The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort (diagnosed &lt;15 months) enrolled SLE patients from 30 centres across 11 countries from 2000 onwards. Clinical, therapeutic and laboratory data were collected according to a standardised protocol. Using data from the enrolment visit, univariate analysis and multivariate regression were used to assess the relationship of individual variables with body mass index (BMI). <h3>Results</h3> 1446 patients were studied. There were 1297 (89.7%) women, and at enrolment the cohort had a mean (SD) age and disease duration of 35.2 (13.4) years and 23.9 (17.9) weeks respectively. 593 patients (41.0%) had a BMI≥25 kg/m<sup>2</sup> including 248 (17.1%) who were obese (BMI≥30 kg/m<sup>2</sup>). The prevalence of BMI≥25 kg/m<sup>2</sup> amongst ethnicities varied and was 46.3% in Caucasians (294/634), 56.6% in those of African Ancestry (123/218), 11.8% in Koreans (20/169), 45.3% in Hispanics (108/238). In a multivariable analysis, BMI≥25 was independently associated with age (OR 1.02, 95% CI 1.004, 1.03), hypertension (OR 1.87, 95% CI 1.34, 2.62), African ancestry (OR 2.66, 95% CI 1.48, 4.77) and Hispanic race/ethnicity (OR 1.62, 95% CI 1.01, 2.60). Overweight patients were also more likely to have fasting hyperglycemia (OR 1.46, 95% CI 1.08, 1.97) and the Metabolic syndrome (OR 2.35, 95% CI 1.83, 3.03). No association with disease activity, therapy or self-reported physical activity was found. <h3>Conclusions</h3> In a relatively young, recently diagnosed SLE cohort being overweight was a common cardiovascular risk factor and seemed not to be associated with steroid use. Increased weight is associated with additional CV risk factors in the context of SLE and so should be a target for intervention in this high risk population. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3158
Case 18-1992
Authors: S.M. Helfgott, J.L. Niles, R.T. McCluskey
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 52-year-old man was admitted to the hospital because of asthma, peripheral neuropathy, and eosinophilia.There was a long history of recurrent sinusitis and nasal polyposis. Three years before entry bronchial asthma developed and was triggered by upper respiratory tract infections and cold weather. Extracts of allergens were injected during the one or two years before entry. Four months before admission dyspnea and right-sided chest pain appeared, accompanied by paresthesias in the fingers of both hands. The patient was admitted to another hospital, where he was found to have atrial fibrillation. The white-cell count was 11,000 (11 . . .
Number of people with health insurance has risen by 9.3 million since Affordable Care Act, US study finds
Authors: M. McCarthy
Journal: BMJ (2014)

At least 9.3 million more US people now have health insurance than before the launch of the health insurance exchanges created by the Affordable Care Act, a new report has said. The RAND Corporation, a non-partisan policy research organization, said that this increase had reduced the United States’ uninsurance rate from 20.5% to 15.8%.1

For the report the RAND researchers analyzed data collected by RAND’s Health Reform Opinion Study, an ongoing project that has surveyed the insurance status of a nationally representative panel of people every month since November 2013. 

The new report looks at changes in insurance enrollment from September 2013 to …
Are There Rab GTPases in Archaea?
Authors: Jaroslaw Surkont, Jose B. Pereira-Leal
Journal: Molecular Biology and Evolution (2016)

A complex endomembrane system is one of the hallmarks of Eukaryotes. Vesicle trafficking between compartments is controlled by a diverse protein repertoire, including Rab GTPases. These small GTP-binding proteins contribute identity and specificity to the system, and by working as molecular switches, trigger multiple events in vesicle budding, transport, and fusion. A diverse collection of Rab GTPases already existed in the ancestral Eukaryote, yet, it is unclear how such elaborate repertoire emerged. A novel archaeal phylum, the Lokiarchaeota, revealed that several eukaryotic-like protein systems, including small GTPases, are present in Archaea. Here, we test the hypothesis that the Rab family of small GTPases predates the origin of Eukaryotes. Our bioinformatic pipeline detected multiple putative Rab-like proteins in several archaeal species. Our analyses revealed the presence and strict conservation of sequence features that distinguish eukaryotic Rabs from other small GTPases (Rab family motifs), mapping to the same regions in the structure as in eukaryotic Rabs. These mediate Rab-specific interactions with regulators of the REP/GDI (Rab Escort Protein/GDP dissociation Inhibitor) family. Sensitive structure-based methods further revealed the existence of REP/GDI-like genes in Archaea, involved in isoprenyl metabolism. Our analysis supports a scenario where Rabs differentiated into an independent family in Archaea, interacting with proteins involved in membrane biogenesis. These results further support the archaeal nature of the eukaryotic ancestor and provide a new insight into the intermediate stages and the evolutionary path toward the complex membrane-associated signaling circuits that characterize the Ras superfamily of small GTPases, and specifically Rab proteins.
Abstract 2002: OCT-3/4 expression is associated with high levels of the pro-apoptotic BH3 only protein NOXA in testicular germ cell tumors (TGCTs)
Authors: Matthias Gutekunst, Thomas Mueller, Andrea Weilbacher, Michael A. Dengler, Stephan Kruck, Jens Bedke, Walter E. Aulitzky, Heiko van der Kuip
Journal: Cancer Research (2012)

Abstract Embryonal carcinoma (EC) cells are the pluripotent precursors of differentiated structures of testicular germ cell tumors (TGCT) characterized by expression of the embryonal transcription factor OCT-3/4. Loss of OCT-3/4 during differentiation abrogates the extraordinary high sensitivity to cisplatin in these cells. We previously observed a constitutively high expression level of NOXA and a major role of this pro-apoptotic BH3-only protein for cisplatin hypersensitivity in the EC cell lines NTERA-2D1 and 2102EP. We now investigated if these high NOXA protein levels may be directly linked to the OCT-3/4 status in TGCT cells. Therefore, we analyzed NOXA protein expression in an extended TGCT cell line panel of 5 OCT-3/4 negative and 5 OCT-3/4 positive cell lines. Importantly, NOXA protein was highly correlated with OCT-3/4 levels and also with cisplatin sensitivity. These data indicate that constitutively high NOXA levels might be responsible for the low threshold for cisplatin-induced apoptosis in OCT-3/4 positive pluripotent cells. A direct link between OCT-3/4 and NOXA could also be demonstrated by RNAi mediated silencing experiments performed in NTERA-2D1 and 2102EP cells. Silencing of OCT-3/4 resulted in a significant downregulation of NOXA transcript and an almost complete loss of NOXA protein accompanied by a loss of cisplatin sensitivity. This was observed in both differentiation competent NTERA-2D1 cells as well as in differentiation incompetent 2102EP cells pointing to a direct OCT-3/4 dependent NOXA regulation rather than a bystander effect of differentiation upon loss of OCT-3/4. We further validated our in vitro data by comparing OCT-3/4 and NOXA expression levels in patient samples derived from ECs with other non-seminomatous GCTs, seminomas, and tumor entities from lung, breast, and ovary. In agreement with our in vitro observations, OCT-3/4 and NOXA were found to be highly expressed selectively in seminomas and ECs. This could also be confirmed on protein level in primary tissue samples derived from 5 ECs and 8 seminomas by western blot analysis. In conclusion, our data for the first time demonstrate a close correlation between OCT-3/4 and NOXA protein levels and strengthen the previously hypothesized role of constitutively high NOXA levels for the exquisite sensitivity of TGCTs to cisplatin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2002. doi:1538-7445.AM2012-2002
Comment on “An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice”
Authors: Johan Fredrik Emilsson, Ulf Andreasson, Kaj Blennow, Elias Eriksson, Henrik Zetterberg
Journal: Science Translational Medicine (2014)

A study attempts to replicate the finding that the serotonin reuptake inhibitor citalopram decreases amyloid β concentrations in the cerebrospinal fluid of healthy volunteers.
“Daily” Dialysis — Lessons from a Randomized, Controlled Trial
Authors: Zbylut J. Twardowski, Madhukar Misra
Journal: New England Journal of Medicine (2010)

The frequency of dialysis was established at three times a week in 1965,1 and this frequency has been used in most centers around the world. Soon after the establishment of this dialysis schedule, an analogue simulation concluded that daily (also known as quotidian) short dialysis sessions would be more effective than thrice-weekly longer dialysis sessions in lowering the average concentration of various markers, such as urea, which rapidly equilibrate among body-fluid compartments.2 With thrice-weekly hemodialysis, the relatively long interval between dialysis sessions results in a "peak-and-valley" effect characterized by fluctuations in the levels of toxins and body-fluid volume, affecting the . . .