tbuckley/cabot-search huggingface dataset:
A Novel HSP90 Inhibitor–Drug Conjugate to SN38 Is Highly Effective in Small Cell Lung Cancer
Authors: Anna V. Gaponova, Anna S. Nikonova, Alexander Y. Deneka, Meghan C. Kopp, Alexander E. Kudinov, Natalia Skobeleva, Vladimir Khazak, Luisa S. Ogawa, Kathy Q. Cai, Kelly E. Duncan, James S. Duncan, Brian L. Egleston, David A. Proia, Yanis Boumber, Erica A. Golemis
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive disease representing 12% to 13% of total lung cancers, with median survival of &amp;lt;2 years. No targeted therapies have proven effective in SCLC. Although most patients respond initially to cytotoxic chemotherapies, resistance rapidly emerges, response to second-line agents is limited, and dose-limiting toxicities (DLT) are a major issue. This study performs preclinical evaluation of a new compound, STA-8666, in SCLC. Experimental Design: To avoid DLT for useful cytotoxic agents, the recently developed drug STA-8666 combines a chemical moiety targeting active HSP90 (concentrated in tumors) fused via cleavable linker to SN38, the active metabolite of irinotecan. We compare potency and mechanism of action of STA-8666 and irinotecan in vitro and in vivo. Results: In two SCLC xenograft and patient-derived xenograft models, STA-8666 was tolerated without side effects up to 150 mg/kg. At this dose, STA-8666 controlled or eliminated established tumors whether used in a first-line setting or in tumors that had progressed following treatment on standard first- and second-line agents for SCLC. At 50 mg/kg, STA-8666 strongly enhanced the action of carboplatin. Pharmacokinetic profiling confirmed durable STA-8666 exposure in tumors compared with irinotecan. STA-8666 induced a more rapid, robust, and stable induction of cell-cycle arrest, expression of signaling proteins associated with DNA damage and cell-cycle checkpoints, and apoptosis in vitro and in vivo, in comparison with irinotecan. Conclusions: Together, these results strongly support clinical development of STA-8666 for use in the first- or second-line setting for SCLC. Clin Cancer Res; 22(20); 5120–9. ©2016 AACR.
Growth Inhibition of Chick-Embryo Cells by Some 5-Fluorinated Pyrimidiness: Effect on Rous Sarcoma Virus Infection&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Rich, Marvin A., Stonehill, Elliott H., Eidinoff, Maxwell L.
Journal: JNCI Journal of the National Cancer Institute (1960)

Journal Article Growth Inhibition of Chick-Embryo Cells by Some 5-Fluorinated Pyrimidiness: Effect on Rous Sarcoma Virus Infection Get access Marvin A. Rich, Marvin A. Rich Division of Biophysics, Sloan-Kettering Institute, Rye, New York, and Sloan-Kettering Division of Cornell University, Medical College, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Elliott H. Stonehill, Elliott H. Stonehill Division of Biophysics, Sloan-Kettering Institute, Rye, New York, and Sloan-Kettering Division of Cornell University, Medical College, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Maxwell L. Eidinoff Maxwell L. Eidinoff Division of Biophysics, Sloan-Kettering Institute, Rye, New York, and Sloan-Kettering Division of Cornell University, Medical College, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 25, Issue 6, December 1960, Pages 1355–1363, https://doi.org/10.1093/jnci/25.6.1355 Published: 01 December 1960 Article history Received: 21 June 1960 Published: 01 December 1960
236O A randomized phase III study comparing neoadjuvant chemotherapy followed by concurrent chemo-radiotherapy with concurrent chemo-radiotherapy in Asian-Indian (South Asian) population with muscle invasive bladder cancer
Authors: S.L. Jakhar, S. Sharma, G. Singh, T. Kothari, N. Sharma, S.K. Beniwal, H.S. Kumar, R. Sinwar, M. P
Journal: Annals of Oncology (2015)
FRI0263 PTX3 and TSG-6 Identify Specific Disease Subsets in Anca-Associated Vasculitides
Authors: G.A. Ramirez, M. Blasi, B. Bottazzi, S. Valentino, E. Tombetti, M.G. Sabbadini, P. Rovere-Querini, A. Mantovani, A.A. Manfredi
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> More accurate Anti Neutrophil Cytoplasmic Antibodies (ANCA) – associated vasculitides (AAV) biomarkers could yield clues about the pathogenesis and improve patients monitoring during follow-up. The long pentraxin PTX3 is an emerging marker of acute inflammation and vessel injury. Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) is an anti-inflammatory signal often co-expressed with PTX3 by leukocytes and endothelial cells. <h3>Objectives</h3> To evaluate the possible correlations among PTX3, TSG-6 and AAV clinical features. <h3>Methods</h3> Upon informed consent, clinical data (including disease activity at the time of venepuncture, as estimated by the Bimingham Vasculitis Activity Score, BVAS) and blood samples were collected from 63 consecutive patients with AAV (38 with granulomatosis with polyangiitis, GPA), 15 with eosinophilic granulomatosis with polyangiitis, EGPA, 10 with microscopic polyangiitis, MPA and 57 matched healthy controls (HC). Plasma concentrations of PTX3 and TSG-6 were measured by ELISA and correlated with clinical data. Due to the relatively wide range of TSG-6 levels, logarithmic transformation was applied. Data are expressed as mean ± standard error of mean. <h3>Results</h3> PTX3 levels were higher in patients (4.99±1.19) than in HC (1.61±0.15; p=0.008). In patients with AAV PTX3 levels correlated with the BVAS (p=0.026), C-reactive protein levels (p=0.032), white blood cell count (p=0.007) and ANCA titer at the time of blood sample collection (p=0.030). PTX3 levels were higher in patients with pure vasculitic manifestations (9.24±3.91 vs 3.55±0.82 in patients with concomitant granulomatous lesions; p=0.036) and lower in patients with ear-nose-throat (ENT) involvement (p=0.010).TSG-6 levels were lower in AAV patients with ENT involvement (5.77±0.35 vs 4.07±0.76; p=0.021) and correlated with platelet count (p=0.005). PTX3 and TSG-6 leves did not correlate. <h3>Conclusions</h3> PTX3 levels reflect disease activity and vasculitic involvement in AAV. TSG-6 could play a role in identifying patients with prominent ENT involvement and defective clearance of platelets during acute inflammation. <h3>References</h3> Kallenberg CG. Nat Rev Rheumatol. 2014 Milner C et al. J Cell Sci. 2003 Maugeri N et al. Thromb Res. 2012 <h3>Disclosure of Interest</h3> None declared
The detection of bone marrow involvement in small-cell lung cancer using magnetic resonance imaging.
Authors: V Trillet, D Revel, R Loire, J Pages, M Favrot, A Bonmartin, G Salles, P Marion, J F Mornex, J F Cordier
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.2.397 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2828559 The detection of bone marrow involvement in small-cell lung cancer using magnetic resonance imaging. V TrilletxV TrilletSearch for articles by this author , D RevelxD RevelSearch for articles by this author , R LoirexR LoireSearch for articles by this author , J PagesxJ PagesSearch for articles by this author , M FavrotxM FavrotSearch for articles by this author , A BonmartinxA BonmartinSearch for articles by this author , G SallesxG SallesSearch for articles by this author , P MarionxP MarionSearch for articles by this author , J F MornexxJ F MornexSearch for articles by this author , J F CordierxJ F CordierSearch for articles by this author Show More https://doi.org/10.1200/JCO.1988.6.2.397 PDF "The detection of bone marrow involvement in small-cell lung cancer using magnetic resonance imaging.." Journal of Clinical Oncology, 6(2), pp. 397–398© 1988 by American Society of Clinical Oncology
AB1236-HPR Staying Safe Throughout the Day – Preventing Falls at Home
Authors: M. Roffler
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Avoiding falls in the home environment for the elderly is proven as an effective intervention to reduce health costs in society on the one hand and to increase the quality of life and independence of the target group concerned on the other hand. <h3>Objectives</h3> As a result, the Swiss League Against Rheumatism has developed a service to reduce fall risks, which enables a behavioural and environmental preventative assessment of their own home for elderly people at risk of falling. <h3>Methods</h3> Interested persons at risk of falling register themselves directly or via their GP or Spitex at a Swiss League Against Rheumatism coordination site. The coordination site charges specially-trained physiotherapists with assessing guidance. After consultation, examination and assessment, changes are undertaken in the living area that were deemed necessary. Cases of tripping are eliminated. In addition, the elderly are counselled individually and instructed in strength and balance training over 2-3 sessions. After the assessment, a report is drawn up showing the recommended follow-up actions that will be made available by the supervising doctor, the elderly person and, where possible, Spitex. A telephone call-back or a second visit to the elderly person consulted is carried out after approx. 4 weeks. The elderly person will be contacted again by telephone 6 months later. <h3>Results</h3> The service has been tested in the context of a pilot project in the Canton of Lucerne, in which around 100 house visits were carried out. The project has been accompanied by a master9s thesis for ZHAW [Zurich University of Applied Sciences] and evaluated. The results show that the intervention was simple to implement and constructive. Due to the positive feedback from the partners involved and the elderly people, the Swiss League Against Rheumatism is now also introducing this service on a national level. So far, about 400 house visits were successfully carried out. <h3>Conclusions</h3> Additional secondary research in relation to the long-term cost effect and the influence on quality of life of the elderly is planned. With this service, the Swiss League Against Rheumatism wishes to make a contribution towards the independence and quality of life of the elderly. <h3>Disclosure of Interest</h3> None declared
Lesson of the Week: Adrenocortical failure in intensive care
Authors: N F Quiney, M A Durkin
Journal: BMJ (1995)

Diagnosis of acute adrenocortical failure in patients admitted to intensive care units is difficult as the clinical features are non-specific and may mimic those of other conditions. We report on a patient in whom the initial diagnosis of septic shock had to be amended later to acute adrenocortical failure. The criteria for laboratory diagnosis of adrenocortical failure in patients in intensive care may need to be modified as adrenocortical function is altered in patients with severe organ dysfunction.

A 45 year old woman with myasthenia gravis was admitted to intensive care breathless and disoriented. She had a fever, with a temperature of 38°C, and had an arterial pressure of 60/40 mm Hg. Her serum concentration of sodium was 131 mmol/l and of potassium was 4.4 mmol/l. A full blood count showed a haemoglobin concentration of 148 g/l and leukocytosis, with a cell count of 18.9 x 109/l. Despite fluid resuscitation with 2000 ml 0.9% saline and 1000 ml gelatin (Haemaccel) she remained hypotensive. A pulmonary artery catheter was inserted, and the haemodynamic profile showed a normal mean pulmonary artery pressure of 15 mm Hg and cardiac index of 3.8 l/min/m2 but a low systemic vascular resistance index of 971 dyne.sec/cm5/m2 and left ventricular stroke work index of 20.7 g/m2/beat.

A presumptive diagnosis of septic shock …
Assessment of cardiovascular risk in primary care
Authors: Salman Waqar, Faraz Mughal, Ahmed Rashid, Jonathan Mant
Journal: BMJ (2016)

A 41 year old white man presented to his general practitioner for a routine blood pressure check. He was asymptomatic and had an initial reading of 154/115 mm Hg. Subsequent ambulatory blood pressure monitoring (ABPM) showed that the average daytime reading was 137/89 mm Hg.

On further assessment he had no evidence of left ventricular hypertrophy on electrocardiography, and no silver wiring or other abnormalities were found on funduscopy. Laboratory tests showed total cholesterol 6.8 mmol/L (reference range  1). There was no evidence of urinary microalbuminuria.

He drank a moderate amount of alcohol at weekends only and smoked 10 cigarettes a day. He had a medical history of depression and dyspepsia for which he took sertraline and omeprazole daily. He had no family history of cardiovascular disease (CVD).

His QRISK2 score was calculated as 10.3%. He was worried about what this meant for his health and wanted help in making decisions about how to proceed.

1.  Which guidelines and tools could help facilitate a discussion that leads to shared decision making with the patient?

2.  What are the important principles of lifestyle advice to deliver?

3.  Is drug treatment indicated in this patient?

4.  When is referral to secondary care warranted?

### 1. Which guidelines and tools could help facilitate a discussion that leads to shared decision making with the patient?

#### Short answer

The National Institute for Health and Care Excellence (NICE) has developed a clinical guideline (CG181) on lipid modification for primary and secondary prevention of CVD.1 Patient decision aids present evidence based estimates of the risks and benefits of treatment options to help facilitate shared patient focused decision making.

#### Discussion

The NICE guideline offers evidence based advice and recommendations on the treatment of people currently with, or at risk of, CVD. International guidelines from the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) also provide robust guidance tailored …
MEN1112, a Novel Humanized De-Fucosylated Monoclonal Antibody with High Affinity and Specificity for Bst1/CD157 Antigen and Enhanced CD16 Binding
Authors: Dee Aud, Rachel Dusek, Arnima Bisht, Sudha Swaminithan, Rahel Awdew, Michael Trang, San Lin Lou, Stefano Manzini, Alfredo Martinez Mogarra, Alessandro Bressan, Jon Terrett, Monica Binaschi
Journal: Blood (2014)
SAT0261 Asdas can be Reliably Calculated When Only the Patient's Overall Basdai Score is Available, but not the Score(S) of its Individual Component(S): Table 1.
Authors: P. Cetin, G. Kenar, S. Capar, H. Yarkan, B. Zengin, I. Sari, M. Birlik, F. Onen, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> ASDAS is a composite measure of disease activity for ankylosing spondylitis (AS). Its calculation includes three BASDAI questions, BASDAI Q2 (back pain), Q3 (peripheral pain/swelling), and Q6 (morning stiffness), plus ESR or CRP, depending on the version. In many patients9 clinical records, BASDAI total score is included but the scores of its individual components are missing. <h3>Objectives</h3> Our aim was to assess the validity of imputing missing BASDAI items from the overall BASDAI score in order to calculate the patient9s ASDAS in such a clinical situation. <h3>Methods</h3> Patients with complete baseline data for ASDAS and BASDAI components were identified from our local AS database. Original ASDAS calculations were repeated by replacing each or all of the BASDAI items included in the formula with the overall BASDAI score. Kappa statistics was used to assess the agreement between the original and the imputed ASDAS scores, in classifying patients into different disease activity states (inactive, moderate, high and very high). The mean difference between scores was calculated. The analysis was completed with the <i>Bland–Altman</i> method. <h3>Results</h3> 403 patients with AS (age 44.4±11.8 years; 73.7% males) with a mean disease duration of 9.7±8.1 years were included in this analysis. Their mean (SD) BASDAI, ASDAS-CRP and ASDAS-ESR scores were 3.6 (2.3), 3.1 (1.1), and 3.1 (1.1), respectively. Kappa values ranged from 0.80 to 0.89 (weighted kappa values from 0.84 to 0.96), with lower limits of the 95%CI all over 0.75 in the different imputation schemes (Table 1). The largest mean difference between the original and the imputed scores was 0.17. <h3>Conclusions</h3> The close agreement between the original and the imputed ASDAS scores observed in this analysis support the validity of imputing missing BASDAI items from the overall BASDAI, when the score(s) of its individual component(s) are lacking. <h3>Disclosure of Interest</h3> None declared
AVAglio: A phase III trial of bevacizumab added to standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.
Authors: O. L. Chinot, W. Wick, F. Saran, W. P. Mason, R. Henriksson, R. Nishikawa, A. H. Zeaiter, N. Moore, A. Das, T. F. Cloughesy
Journal: Journal of Clinical Oncology (2011)

TPS136 Background: Despite therapeutic advances in standard of care (SOC), glioblastoma (GBM) remains a devastating disease with a dismal prognosis. In patients with recurrent GBM, bevacizumab (BEV) has demonstrated activity, as measured by objective response rate (ORR) and 6-month progression free survival (PFS), compared with historical controls. The addition of BEV to SOC may add clinical benefit and provide a treatment advantage for patients with newly diagnosed GBM. Methods: In this randomized, double-blind, placebo (PLA)-controlled, multicenter trial, patients ≥18 years with newly diagnosed, histologically confirmed supratentorial GBM will receive SOC radiotherapy (RT; 2 Gy 5 days/wk for 6 wks) and temozolomide (TMZ; 75 mg/m2/day oral) with biweekly BEV or PLA (10 mg/kg intravenous). After completion of RT and a 28-day TMZ-free period, patients will receive TMZ for 5 days every 4 wks (150 mg/m2/day daily, with potential to escalate to 200 mg/m2/day) and biweekly BEV or PLA for 6 cycles or until unacceptable toxicity or disease progression (PD). Subsequently, patients will receive single-agent BEV or PLA (15 mg/kg every 3 wks) until unacceptable toxicity or PD. Co-primary endpoints are investigator-assessed PFS and overall survival. Secondary endpoints are independent radiology review-assessed PFS, 1- and 2-year survival rates, safety, and health-related quality of life. Exploratory endpoints include ORR; duration of response; corticosteroid use; and correlative analyses of biomarkers with efficacy. The protocol was amended in January 2010 to include additional measures of clinical benefit, including the following exploratory endpoints: neurocognitive function, signs and symptoms of disease, Karnofsky performance score, and patterns of PD. First patient was randomized June 29, 2009. The Data Monitoring Committee reviewed the trial on January 19, 2011 and recommended that it continue as planned.
THU0328 Secondary Fibromyalgia in Patients with Other Rheumatic Diagnoses: Clues for Recognition on a Multidimensional Health Assessment Questionnaire (MDHAQ) and Physician Rheumetric Checklist
Authors: T. Pincus, E. Nikiphorou, A. Huang, I. Castrejon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> About 20-40% of patients with various rheumatic conditions are recognized to have concomitant comorbid fibromyalgia (FM), which often complicates patient management. Secondary FM may be difficult to recognize in patients who meet criteria for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and other diseases. A 2-page multidimensional health assessment questionnaire (MDHAQ) and 2-page RHEUMETRIC checklist include scales that provide clues to FM. <h3>Objectives</h3> To analyze MDHAQ and RHEUMETRIC scales to assess overall patient status (DOCGL), inflammation (reversible signs) (DOCINF), damage (irreversible signs) (DOCDAM) and neither inflammation nor damage (DOCNON), e.g., fibromyalgia. <h3>Methods</h3> All patients seen in a clinical setting complete a 2-page MDHAQ in 5-10 minutes in the waiting area, prior to seeing the rheumatologist in routine care. The MDHAQ includes scores for physical function (FN) in 10 activities scored 0-3, total 0-30 converted to 0-10, three 0-10 visual analog scales (VAS) for pain (PN), patient global score (PATGL) and fatigue (FT), and a 0-60 item symptom checklist and demographic data. RAPID 3 (0-30) is the sum of scores for FN, PN and PATGL. RHEUMETRIC is a one-page physician checklist with four 0-10 VAS physician global estimates to assess DOCGL, DOCINF, DOCDAM, and DOCNON, e.g., fibromyalgia in patients with various rheumatic diseases who were designated by their rheumatologists as having or not having secondary FM. All patients were classified as having or not having a secondary diagnosis of FM, and compared for mean scores on MDHAQ and RHEUMETRIC scales, using t tests to analyze statistical significance. <h3>Results</h3> Of 311 patients with various rheumatic diagnoses other than FM, 294 (94.5%) did not and 17 (5.6%) did have a diagnosis of secondary FM - a likely underestimate of the true prevalence. Mean scores on each of the MDHAQ scales were 1.5-3 fold higher in patients with secondary FM versus no FM (Table). DOCGL was higher in patients with secondary FM compared to those with no FM, while DOCINF and DOCDAM did not differ significantly in the 2 groups (Table). Mean DOCNON on RHEUMETRIC was 5.4 in patients with FM, versus 1.3 in those with no FM, a 4-fold difference (p&lt;0.001). <h3>Conclusions</h3> Simple patient and physician questionnaires can provide useful clues to recognize secondary FM in patients with other primary rheumatic diagnoses. <h3>Disclosure of Interest</h3> None declared
Prevention of Irradiation-Induced Lymphoid Tumors in C57BL Mice by Spleen Protection2
Authors: Egon Lorenz, Charles C. Congdon, Delta Uphoff
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article Prevention of Irradiation-Induced Lymphoid Tumors in C57BL Mice by Spleen Protection Get access Egon Lorenz, Egon Lorenz Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles C. Congdon, Charles C. Congdon Search for other works by this author on: Oxford Academic PubMed Google Scholar Delta Uphoff Delta Uphoff Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 2, October 1953, Pages 291–301, https://doi.org/10.1093/jnci/14.2.291 Published: 01 October 1953 Article history Received: 23 April 1953 Published: 01 October 1953
Meningitis
Authors: Janet M. Torpy, Cassio Lynm, Richard M. Glass
Journal: JAMA (2007)

MeningitisM eningitis (infection of the coverings of the brain and spinal cord) is a serious illness.Meningitis can occur in adults and children, even in infants, and can be caused by viruses, bacteria, fungi, or parasites.Bacterial meningitis can be fatal or cause severe impairment, particularly if the diagnosis of bacterial meningitis is delayed, but can be treated, especially when diagnosed early in the disease.The common types of bacteria that can cause meningitis are Neisseria meningitidis (also known as meningococcus) and Streptococcus pneumoniae (pneumococcus).These bacteria are highly contagious, spread rapidly, and can be deadly.Nursing homes, college dormitories, day care centers, and schools are often sites of outbreaks of meningitis.Vaccines are available for some bacteria and can be helpful to stop spread of contagious meningitis.The January 3, 2007, issue of JAMA includes an article about meningitis in children.
LP36 : Understanding hepatitis delta virus and HBsAG kinetics during treatment with prenylation inhibitor lonafarnib via mathematical modeling
Authors: L. Canini, C. Koh, S.J. Cotler, X. Zhao, S.L. Uprichard, V. Haynes-Williams, M.A. Winters, G. Subramanya, S.L. Cooper, P. Pinto, E. Wolff, R. Bishop, M.A. Than Han, D.E. Kleiner, O. Keskin, R. Idilman, C. Yurdaydin, J.S. Glenn, T. Heller, H. Dahari
Journal: Journal of Hepatology (2015)