tbuckley/cabot-search huggingface dataset:
Diverse Immunocytologic Findings of Nasal Smears in Influenza
Authors: Isao Tateno, Osamu Kitamoto, Akiyoshi Kawamura
Journal: New England Journal of Medicine (1966)

EVIDENCE that the rapid diagnosis of influenza might be possible by means of fluorescent-antibody technic was first presented by Liu1 , 2 This finding was confirmed by Japanese3 , 4 and Czechoslovakian5 , 6 workers. We modified the technic of Liu in obtaining nasal epithelial cells and extended the experiment further. The only difference between his and our technics was that we obtained the nasal smears directly from the nasal cavity by means of a cotton swab instead of using nasal washings. This modification enabled us to obtain abundant nasal epithelial cells readily at outpatient clinics, at bedside or at home visits. During the recent epidemic . . .
The Treatment of Ureters Injured during Gynecologic Operations
Authors: Francis M. Ingersoll, Joe V. Meigs
Journal: New England Journal of Medicine (1945)

ACCIDENTAL injury of a ureter is the most frequent serious complication of gynecologic pelvic operations. This fact was brought to our attention by the occurrence of 7 ureteral injuries in 590 total hysterectomies and 1 ureteral injury in 170 supravaginal hysterectomies done during a five-year period at the Massachusetts General Hospital. These 8 cases will serve to illustrate the type of injuries that occur and the surgical principles and procedures to be followed in repairing them.Principles of TreatmentAlthough each patient must be treated according to the circumstances of the case, there are certain important principles that should be . . .
Does Motion Analysis in Postexercise Gated Sestamibi SPECT Reflect Rest Left Ventricular Motion Even in Severe Coronary Artery Disease?
Authors: THOMAS LEITHA, MARIANNE GWECHENBERGER, MARTHA PRUCKMAYER, ANTON STAUDENHERZ, HARTWIG BAILER, GERHARD KRONIK
Journal: Clinical Nuclear Medicine (2001)

Purpose Evidence has suggested that postexercise gated Tc-99m sestamibi SPECT (GSPECT) provides combined information about resting wall motion and exercise perfusion. No data have been published about possible differences in wall motion analysis between postexercise and resting GSPECT. Methods Fifty patients underwent postexercise (symptom-limited bicycle stress) and rest GSPECT and cardiac catheterization with contrast ventriculography. In 35 patients, additional rest planar Tc-99m RBC radionuclide ventriculography (RNV) was performed. Four observers independently performed left ventricular ejection fraction (LVEF) calculations and visual analysis of regional wall motion (graded in four stages) for all studies. Results The LVEF calculations in GSPECT revealed a statistically significant difference between postexercise (45.8 ± 15.7%) and rest (48.0 ± 16.1%;P < 0.05) determination. Postrest GSPECT LVEF showed a better correlation with LVEF determination performed with contrast ventriculography and RNV than did postexercise GSPECT LVEF. The reduced postexercise wall motion could be shown in segments with exercise-induced ischemia and in those with normal regional perfusion but not in segments with irreversibly abnormal perfusion. Conclusions Postexercise GSPECT provides reliable information regarding global wall motion even in severe coronary artery disease, but regional wall motion is underestimated compared with rest GSPECT, because of an imprecise surface detection algorithm in ischemic wall segments and possibly postexercise stunning in severe coronary artery disease.
A2.1 The effect of mPGES-1 deletion on platelet function in mice
Authors: J Raouf, F Mobarrez, K Larsson, PJ Jakobsson, M Korotkova
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible terminal synthase that generates PGE<sub>2</sub> and is one of the key players in inflammation. Genetic deletion and pharmacological inhibition of mPGES-1 are protective in experimental models of inflammation. Platelets play essential roles in homeostasis and modulation of inflammatory processes, activated platelets have been recognised as major players in autoimmune diseases such as rheumatoid arthritis. Targeting mPGES-1 alters eicosanoid profiles and may potentially regulate functions of platelets that are known to express prostanoid receptors. <h3>Objective</h3> To investigate the effect of mPGES-1 deletion on platelet function in mice stimulated with LPS. <h3>Methods</h3> Wild type (WT) and mPGES -/- (KO) mice (DBA/1lacJ) were injected with 2 μg LPS (n = 6) or saline (n = 5) i.p, for 24 h. Mice were anesthetised and blood was slowly drawn by a syringe containing 100 μl 3.8% sodium citrate and transferred to tubes containing citrate to avoid platelet activation. Platelets were stained with CD41-PE together with CD62-FITC (P-selectin) or CD154-FITC (CD40L) and analysed by whole blood flow cytometry. Platelet activation and platelet-leucocyte interaction was also investigated after ADP stimulation (10 μM). <h3>Results</h3> Platelet counts decreased after LPS stimulation in WT mice. P-selectin expression was higher in LPS-induced WT compared with KO mice. CD40L expression was higher after LPS stimulation for both WT and KO mice. The platelet-leukocyte interaction seems to be lower in KO mice. There were no differences in platelet activation after ADP stimulation between WT and KO mice. <h3>Conclusions</h3> mPGES-1 deletion affected platelet counts and activation in LPS stimulated mice. The data suggest possible role of mPGES-1 in platelet function during inflammation.
PVL - encoding Staphylococcus aureuspresenting as a community acquired subdural empyema with meningitis by Tejal Desai (1), David Garner (2) and Nigel Cumberland (2)1. Western Sussex Hospitals NHS trust, Worthing, West Sussex2. Frimley Park Hospital NHS Foundation Trust, Surrey
Authors: Tejal Desai, David Garner, Nigel Cumberland
Journal: Journal of Infection (2011)
Abstract 5423: New diazonamide analogs demonstrate remarkably larger therapeutic window compared to taxanes and vinca alkaloids in rodents
Authors: Lin Li, Wei Qi, Ming Zhou, Xiaoming Xu, Patrick G. Harran, Xiaodong Wang, Lai Wang
Journal: Cancer Research (2011)

Abstract Diazonamide A is a natural product originally isolated from a marine organism. It potently induces G2/M cell cycle arrest. Its molecular mode of action is not fully understood but its potential as a cancer therapeutic is high. To streamline our diazonamide synthesis and to define a minimal pharmacophore, we prepared a series of truncated structures. Its simplified structure and shortened synthesis allowed for extensive structure activity relationship analyses. Several modifications markedly improved activity. Among them, JP2295 and JP2362 were studied in details. Both compounds were highly efficacious in a wide spectrum of tumors from different origin both in vitro and in vivo. They were &amp;gt;20 fold more potent than AB5, a closely related analog of the natural product, in a MIA Paca-2 pancreatic cancer xenograft model. At dose 10-fold higher than the efficacious dose, JP2295 or JP2362 did not cause any apparent toxicity. Three out of 7 mice were completely free of tumor even 6 months after the initial treatment. In the same model, taxanes, i.e. paclitaxel and docetaxel, and vinca alkaloids, i.e. vinorelbine, vinblastine, and vincristine, were either less efficacious or causing severe body-weight loss, even animal death. Similar effects were observed in other xenograft models. Safety studies were further carried out in NIH Swiss mice and Sprague Dawley rats with similar results. In summary, JP2295 and JP2362 demonstrated over 20-fold bigger therapeutic window than taxanes and vinca alkaloids in rodents. Such a large therapeutic window is unique for a small molecule anti-mitotic and suggests further development is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5423. doi:10.1158/1538-7445.AM2011-5423
P17.47 * COMPREHENSIVE PROTEOMIC PROFILING OF BEVACIZUMAB-RESISTANT GLIOBLASTOMA MULTIFORME
Authors: K. L. Kaufman, L. Ly, M. McKay, D. M. Mallawaaratchy, S. Mactier, B. Crossett, M. Molloy, M. E. Buckland, K. L. McDonald, R. I. Christopherson
Journal: Neuro-Oncology (2014)

Drugs that impair tumour angiogenesis, i.e. therapeutic antibody anti-vascular endothelial growth factor, bevacizumab (BEV), are becoming standard therapy for recurrent GBM, despite having no impact on overall survival times. Resistance to BEV is fatal, and mechanisms are largely unexplored. With access to exceedingly rare fresh-frozen serial GBM tumours, we performed comprehensive quantitative proteome analyses to identify important mechanisms of BEV escape and tumour recurrence. Tumour tissues from three patients [primary (n = 2), recurrent (n = 2) and post-BEV recurrent (n = 3)] were homogenised, clarified (1,000 x g, 4°C) and ultracentrifuged (100,000 x g, 4°C) to isolate the soluble (SOL) proteome supernatant from the microsomal (MEM) pellet. Digested SOL and MEM proteomes were analysed by two independent quantitative MS/MS approaches; Label-free quantitation performed on spectra obtained in triplicate using an Orbitrap Velos (Thermo Electron) and 4-plex iTRAQ-labelling coupled ERLIC-RP MS/MS analysis using a 5600 TripleTOF® (AB Sciex; single run for MEM; duplicate run for SOL). Spectra were processed using Mascot Distiller, Progenesis, Scaffold and ProteinPilot™ softwares. This multi-centre proteomics project has achieved a number of highly reproducible and comprehensive quantitative proteome datasets (average of 1760 MEM proteins and 2334 SOL proteins identified at 95% confidence levels) from precious serial GBM specimens. Significant differentially abundant proteins include those involved in Rho regulation of actin-based motility and cytoskeleton and endocytosis signalling. Bioinformatics analyses with captured whole exome sequencing data are underway to define novel mechanisms of evasive resistance to BEV in recurrent GBM.
Financial Toxicity of Cancer Care: It’s Time to Intervene
Authors: S. Yousuf Zafar
Journal: JNCI Journal of the National Cancer Institute (2015)

Evidence suggests that a considerably large proportion of cancer patients are affected by treatment-related financial harm. As medical debt grows for some with cancer, the downstream effects can be catastrophic, with a recent study suggesting a link between extreme financial distress and worse mortality. At least three factors might explain the relationship between extreme financial distress and greater risk of mortality: 1) overall poorer well-being, 2) impaired health-related quality of life, and 3) sub-par quality of care. While research has described the financial harm associated with cancer treatment, little has been done to effectively intervene on the problem. Long-term solutions must focus on policy changes to reduce unsustainable drug prices and promote innovative insurance models. In the mean time, patients continue to struggle with high out-of-pocket costs. For more immediate solutions, we should look to the oncologist and patient. Oncologists should focus on the value of care delivered, encourage patient engagement on the topic of costs, and be better educated on financial resources available to patients. For their part, patients need improved cost-related health literacy so they are aware of potential costs and resources, and research should focus on how patients define high-value care. With a growing list of financial side effects induced by cancer treatment, the time has come to intervene on the "financial toxicity" of cancer care.
SAT0344 Does proximal femur shape contribute to femoral neck fracture risk in osteoporotic individuals?:
Authors: A.G.S. Oldroyd, B. Evans, C. Greenbank, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hip Structural Analysis (HSA) has been used to investigate the relationship between proximal femoral neck shape and femoral neck fracture risk; studies have reported contrasting findings. Although previous work has been carried out on the general population, it is not known if a particular proximal femur shape is associated with femoral neck fracture in patients with established osteoporosis (OP). <h3>Objectives</h3> To investigate if HSA measurements differ between osteoporotic patients that have and have not sustained a femoral neck fracture. <h3>Methods</h3> Data were collated from patients diagnosed with OP by DXA between 2006 and 2010 in a UK district general hospital. Two groups were identified: those with and without a previous femoral neck fracture. HSA measurements were compared between the two groups using a logistic regression model, unadjusted and adjusted for possible confounders - age, sex and body mass index (BMI). The following HSA measurements were collated: distance from center of femoral head to center of femoral neck (d1), distance from center of femoral head to inter-trochanteric line (d2), mean femoral neck diameter (d3), distance from center of mass of femoral neck to superior neck margin (y), hip axis length (HAL), cross-sectional moment of inertia (CSMI - theoretical measurement of femoral neck strength) and proximal femur strength index (SI). The previous fracture group's HSA measurements were taken from the contra-lateral non-fractured hip. <h3>Results</h3> Data of 632 (82.58% female) osteoporotic patients that had previously sustained a femoral neck fracture were compared to 11761 (82.50% female) osteoporotic patients that had not previously sustained a femoral neck fracture. The mean age of the fracture group was significantly lower compared to the non-fracture group: 69.21 years vs 70.24 years (p-value 0.01), respectively. Mean BMI did not significantly differ between the fracture and non-fracture groups: 25.86 kg/m<sup>2</sup> vs 26.05 kg/m<sup>2</sup> (p-value 0.29), respectively. Following adjustment for age, sex and BMI, the odds ratios indicate that the fracture group had a significantly higher HAL, d2, d3 and y, and lower CSMI and CSA. <h3>Conclusions</h3> Results indicate that, for osteoporotic individuals, femoral neck fracture is associated with a longer (HAL, d2), wider (d3, y) and theoretically weaker (CSA, CSMI) proximal femur. This study indicates that proximal femur shape is associated with femoral neck fracture risk in osteoporotic individuals. Measurement of proximal femur shape as well as BMD may more accurately quantify femoral neck fracture risk. Proximal femur remodeling following contra-lateral fracture can not be ruled out. <h3>Disclosure of Interest</h3> None Declared
Abstract 246: Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the dynamic equilibrium between cancer stem cells and non-stem cancer cells.
Authors: Seog-Young Kim, Jin W. Kang, Bokyoung Kim, Young D. Yoo, Yong T. Kwon, Yong J. Lee
Journal: Cancer Research (2013)

Abstract Previous studies have demonstrated that a small subset of cancer cells is capable of tumor initiation. The existence of tumor initiating cancer stem cells (CSCs) has several implications in terms of future cancer treatment and therapies. However, recently, several researchers proposed that differentiated cancer cells (non-CSCs) can convert to stem-like cells to maintain equilibrium. These results imply that removing CSCs may prompt non-CSCs in the tumor to convert into stem cells to maintain the equilibrium. Interleukin-6 (IL-6) has been found to play an important role in the inducible formation of CSCs and their dynamic equilibrium with non-stem cells. In this study, we used CSC-like MDA-MB231 human breast adenocarcinoma cells and their alternate subset non-CSCs to investigate how IL-6 regulates the conversion of non-CSCs to CSCs. CSC-like cells formed mammospheres well, whereas most of non-stem cells died by anoikis and only part of the remaining non-stem cells produced viable mammospheres. Similar results were observed in xenograft tumor formation. Data from cytokine array assay show that IL-6 was secreted from non-CSCs when cells were cultured in ultra-low attachment plates. IL-6 regulates CSC-associated OCT-4 gene expression through the IL-6-JAK1-STAT3 signal transduction pathway in non-CSCs. Inhibiting this pathway by treatment with anti-IL-6 antibody (1 μg/ml) or niclosamide (0.5-2 μM)/LLL12 (5-10 μM) effectively prevented OCT-4 gene expression and suppressed mammosphere formation of non-stem cells. These results suggest that the IL-6-JAK1-STAT3 signal transduction pathway plays an important role in the conversion of non-CSCs into CSCs through regulation of OCT-4 gene expression. Citation Format: Seog-Young Kim, Jin W. Kang, Bokyoung Kim, Young D. Yoo, Yong T. Kwon, Yong J. Lee. Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the dynamic equilibrium between cancer stem cells and non-stem cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 246. doi:10.1158/1538-7445.AM2013-246
Abstract 5345: MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis.
Authors: Smrithi Rajendiran, Jamboor K. Vishwanatha
Journal: Cancer Research (2013)

Abstract Migration and invasion enhancer gene 1(MIEN1), previously known as C17orf37, C35, ORB3, XTP4, RDX12, and MGC14832, is located in the 17q12 region of the human chromosome. MIEN1 expression is minimal to negligible in normal cells and tissues compared to its abundant expression in various cancers, including breast, prostate, oral and gastrointestinal carcinomas. MIEN1 works as a signaling molecule through the AKT/NF-κB pathway by up-regulating key proteases, matrix metalloproteinase - 9, urokinase - type plasminogen activator and vascular endothelial growth factor. We have shown that MIEN1 plays an important role in the migration and invasion of cancer through increased filopodia formation, hence promoting metastasis. The overall objective of this study is to identify the mechanisms that lead to the differential regulation of MIEN1 between normal and cancer cells. Our hypothesis is that MIEN1 is post-transcriptionally regulated by specific microRNA(s) that is (are) down-regulated in cancer, thus explaining its aberrant increased expression in cancer. MicroRNA expression profiling pattern predict several microRNAs that can directly bind to 3′UTR of MIEN1 mRNA. In silico analysis followed by northern blotting and real time PCR indicate a novel microRNA that regulates MIEN1 expression. This was further confirmed by decrease or increase in RNA and protein levels of MIEN1 as well as its downstream signaling effectors, upon microRNA mimic or inhibitor addition, respectively. Direct binding of the microRNA with MIEN1 mRNA was further confirmed by luciferase reporter assays, while the scratch wound healing and tumor invasion assays showed the functional significance of this microRNA on migration and invasion. Since the importance of MIEN1 as a key signaling molecule in cancer is well established, understanding the mechanism(s) involved in the regulation of MIEN1 will aid in designing novel and effective therapeutic strategies to treat cancer patients. Citation Format: Smrithi Rajendiran, Jamboor K. Vishwanatha. MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5345. doi:10.1158/1538-7445.AM2013-5345
BI-13 * TISSUE TRANSGLUTMINASE: A POTENTIAL ADJUVANT TARGET FOR PRIMARY BRAIN TUMOR
Authors: Y.-C. Huang, H.-y. Chen, D.-h. Yeh, K.-C. Wei
Journal: Neuro-Oncology (2014)

Tissue transglutaminase, upregulated by TGFβ, is also highly expressed in primary brain tumors, including gliomas and meningiomas by expression profile microarray. Direct knockdown of transglutminase induced arrest of cell proliferation and cell apoptosis in brain tumor cells. Higher expression of transglutaminase in meningioma tissue correlated to the WHO grading and recurrence. With competitive inhibition by cystamine to the transglutaminase, the cells presented with decreased AKT phosphorylation and increased c-Jun phosphorylation. The addition of cystamine also increase the expression of cleaved caspase-3 and TUNEL stainings. Furthermore, the S6 ribosome phosphorylation significantly increased, implied the blocking of mTOR pathway. In clonclusion, transglutaminase, possibly linked to TGFβ, maybe a potential adjuvant therapeutic target by decrease of cell proliferation and induction of apoptosis in primary brain tumors.
FRI0220 Sustained clinical efficacy after multiple courses of rituximab in rheumatoid arthritis patients with inadequate response to tumour necrosis factor inhibitors: 2-year data from the repeat (repeated courses in routine clinical practice) study
Authors: C. Codreanu, I. Ancuta, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the last decade, biologic therapy changed dramatically treatment options for rheumatoid arthritis (RA). However, a significant number of patients failed to maintain the initial response to a TNF blocker. More information is needed regarding efficacy and safety of multiple courses of biologics administered over extended periods of time. <h3>Objectives</h3> To assess clinical efficacy of subsequent courses with Rituximab (RTX) in patients with moderate-severe active RA despite treatment with a TNF inhibitor in routine clinical practice in Romania. <h3>Methods</h3> In this open-label, multicentre, prospective observational study started in 2010, patients were treated with RTX at each 6 months. Clinical efficacy was assessed at baseline and after each retreatment course at 6, 12, 18 and 24 months. Clinical assessments included DAS-28, SDAI and CDAI. <b>Δ</b> DAS-28, <b>Δ</b> SDAI and <b>Δ</b> CDAI were calculated based on two consecutive evaluations. Statistical analyses: STATA SE 11.0 software, unpaired t-tests and Pearson correlation coefficients R<sup>2</sup> in regression analysis (for <b>Δ</b> DAS-28, <b>Δ</b> SDAI and <b>Δ</b> CDAI) and Cuzick non-parametric trend tests across ordered groups (for disease activity state). <h3>Results</h3> 943 adult (&gt;18 years) patients with active RA and inadequate response to at least one TNF inhibitor received initial RTX treatment. Median clinical disease activity scores steadily decreased after each retreatment indicating improvement in clinical response: <h3>Conclusions</h3> Our study showed a sustained improvement of clinical response after each retreatment course with RTX (at 6 months interval), regardless of assessment tool used (DAS28, SDAI or CDAI). Each RTX course led to an increased and cumulative clinical response versus the previous one with respect to Treat to Target principles and EULAR/ACR recommendations. <b>Disclosure of Interest</b>: None Declared