tbuckley/cabot-search huggingface dataset:
OP0062 The Predictive Value of Magnetic Resonance Imaging for Radiographic Progression over 5 Years in Hand Osteoarthritis: Table 1
Authors: I.K. Haugen, B. Slatkowsky-Christensen, S. Sesseng, D. van der Heijde, T.K. Kvien
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Hand osteoarthritis (OA) is usually a slowly progressing disease. Some patients show a more rapid progression, leading to considerable pain and disability. Currently, we have limited evidence for predictors for hand OA progression. Magnetic Resonance Imaging (MRI) can visualize the whole joint, providing valuable information about inflammatory and structural features. Due to lack of longitudinal hand OA studies, in which MRI has been obtained, it is unknown whether MRI can predict future radiographic progression. <h3>Objectives</h3> To examine whether MRI features can predict radiographic progression 5 years later in hand OA patients. <h3>Methods</h3> We included 74 patients (67 women) from the Oslo hand OA cohort with a mean (SD) age of 67.9 (5.3) years. They underwent MRI of the 2nd-5th interphalangeal joints of the dominant hand at baseline (2008-09) and hand radiographs at baseline (2008-09) and follow-up (2013). Pre-and post-Gadolinium T1w fat-suppressed images and Short Tau Inversion Recovery (STIR) images were obtained in a 1.0 T extremity scanner. Eight patients had no post-Gadolinium images, and additionally one patient had STIR images only. The MRIs were scored according to the Oslo hand OA MRI score (1), whereas the paired hand radiographs were scored according to the Kellgren-Lawrence (KL) scale (grade 0-4) with known time sequence. Using Generalized Estimating Equations (unstructured correlation matrix), we evaluated whether presence of MRI features could predict radiographic progression in the same joint (adjusted for age, sex and BMI). Progression was assessed in joints with baseline KL grade 0-3, and was defined as an increase in KL score of ≥1. <h3>Results</h3> Mean (SD) follow-up time was 4.6 (0.4) years. We included 497 joints with KL grade 0-3 in the analyses, of which 120 (24.1%) showed radiographic progression. Baseline bone marrow lesions (BMLs) were associated with radiographic progression (p=0.02), whereas the association was borderline statistically significant for synovitis (p=0.07) (Table 1). <h3>Conclusions</h3> The Oslo hand OA cohort represents the first longitudinal hand OA study, in which MRI has been obtained. Joints with synovitis and BMLs were more likely to progress radiographically, although the association was statistically significant for BMLs only. Future larger studies are needed to confirm our findings. <h3>References</h3> Haugen et al. ARD 2011 Jun;70(6):1033-8. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2220
The cerebellum and cerebral cortex: Contrasting and converging contributions to spatial navigation and memory
Authors: Shane M. O'Mara
Journal: Behavioral and Brain Sciences (1996)

Thach's target article presents a remarkable overview and integration of animal and human studies on the functions of the cerebellum and makes clear theoretical predictions for both the normal operation of the cerebellum and for the effects of cerebellar lesions in the mature human. Commentary is provided on three areas, namely, spatial navigation, implicit learning, and cerebellar agenesis to elicit further development of the themes already present in Thach's paper, [THACH]
Native-Valve Infective Endocarditis — When Does It Require Surgery?
Authors: Steven M. Gordon, Gösta B. Pettersson
Journal: New England Journal of Medicine (2012)

Guidelines, not backed by evidence from randomized trials, strongly recommend urgent surgery for patients with infective endocarditis and congestive heart failure due to valvular regurgitation.1,2 Management algorithms for infective endocarditis have been developed, and a recent study showed that surgery is still required in 50% of patients who receive antibiotics.3 Experience shows that surgery in patients with active infective endocarditis is associated with low mortality.4 Debate continues, however, about the timing of surgery to prevent embolic events when there are large or mobile vegetations or vegetations in particular locations and when patients have severe valve dysfunction but do not . . .
Abstract 2404: TMPRSS2, a type II transmembrane serine protease, alters the prostate tumor microenvironment and promotes metastasis
Authors: Yu Sun, Jared Lucas, Susana Hernandez, Peter Nelson
Journal: Cancer Research (2011)

Abstract Introduction: Extracellular and cell surface proteases play indispensible roles in embryonic development and normal tissue homeostasis. They also contribute to tumor pathology involving cellular invasion and metastasis. As the majority of cancer-related deaths are associated with metastasis, understanding contributors to this process is essential for developing improved treatment strategies. TMPRSS2 is a Type II transmembrane serine protease (TTSP) regulated by androgenic hormones and is expressed preferentially in the human prostate. Recent studies have indicated that TMPRSS2 is expressed highly in primary and metastatic prostate cancers, though functional activities are poorly defined. Methods: To determine the relevance and consequence of TMPRSS2 overexpression in prostate cancer, we generated four transgenic mouse models that overexpress wild-type or mutant variants of human and mouse TMPRSS2 under the control of the prostate-specific probasin promoter (PB-TMPRSS2). We further crossed PB-TMPRSS2 mice with the LADY model of prostate cancer, and evaluated tumor growth and the impact on metastasis. Results: We confirmed that the PB-TMPRSS2 transgenic mouse lines have significantly elevated levels of TMPRSS2 protease in prostate epithelium. Although enhanced TMPRSS2 expression did not affect mouse fertility, we observed disorganization and disruption of the basement membrane of prostate glands, regardless of whether the overexpressed enzyme is of human or mouse origin. Immunohistochemical analysis identified dramatically altered levels of β4-integrin and collagen IV in the prostate glands of TMPRSS2-overexpressing mice, with the most significant changes occurring in ventral and anterior lobes. Histological changes in cell differentiation, proliferation or apoptosis were not observed. While a strain of LADY transgenic mice expressing SV40T antigen under the control of the probasin promoter (PB-SV40T) develop prostate cancer without metastatic spread, crosses with PB-TMPRSS2 mice produced offspring with high rates of metastasis to liver, lung, lymph node and bone. Conclusions: Our study pinpoints a mechanistic pathway by which TMPRSS2 contributes to primary prostate cancer progression and promotes metastasis, paralleling the effects of Hepsin overexpression, a structurally similar protease known to promote metastasis. These results provide support for the development of therapeutic approaches to specifically limit TMPRSS2 proteolytic activity in prostate cancer patients. 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 2404. doi:10.1158/1538-7445.AM2011-2404
Abstract P2-01-14: circulating tumor cells in breast cancer exhibit dynamic changes in epithelial and mesenchymal cell composition
Authors: M Yu, A Bardia, BS Wittner, SL Stott, ME Smas, DT Ting, SJ Isakoff, JC Ciciliano, MN Wells, AM Shah, KF Concannon, LV Sequist, E Brachtel, D Sgroi, J Baselga, S Ramaswamy, M Toner, DA Haber, S Maheswaran
Journal: Cancer Research (2012)

Abstract Epithelial to mesenchymal transition (EMT) has been postulated to contribute to the migration and dissemination of cancer cells, but supporting histopathological evidence is limited. We used a microfluidic device to isolate circulating tumor cells (CTCs), combined with multiplex fluorescent RNA-in-situ hybridization (ISH) and RNA sequencing, to quantify and characterize EMT in breast cancer cells within the bloodstream. Whereas only rare (0.1–10%) cells in the primary tumor expressed both mesenchymal and epithelial markers, such biphenotypic as well as purely mesenchymal cells were enriched among CTCs, across all histological subtypes of breast cancer. Analysis of the therapy response in 8 patients suggest an association of mesenchymal CTCs with disease progression. In an index patient followed longitudinally, fluctuation in epithelial and mesenchymal states was observed as a function of initial response and subsequent resistance to therapy. Mesenchymal markers were predominant in clusters of tumor cells, many of which had adherent platelets. Finally, RNA sequencing of mesenchymal CTC clusters identified TGF-B and other EMT-related signatures, which were absent from more epithelial CTCs. FOXC1, a known regulator of EMT, was abundantly expressed in mesenchymal CTCs and was detectable within localized regions of the primary breast tumor. Together, these data support a role for EMT in the blood-borne dissemination of breast cancer and point to the dynamic nature of this cell fate change. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-14.
Development and validation of a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014
Authors: M Y Hindiyeh, J Moran-Gilad, Y Manor, D Ram, L M Shulman, D Sofer, E Mendelson
Journal: Eurosurveillance (2014)

Binary file ES_Abstracts_Final_ECDC.txt matches
MARKERS OF EXTRACELLULAR MATRIX TURNOVER AND RISK OF DEATH IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: RESULTS FROM I-PRESERVE
Authors: Sheryl L. Chow, Henry Krum, Stephen A. O’Barr, Michael Zile, Peter Carson, Michel Komajda, John McMurray, Inderjit Anand
Journal: Journal of the American College of Cardiology (2015)
Chemotherapy of Solid Tumors with Triethylene Thiophosphoramide
Authors: Jeanne C. Bateman
Journal: New England Journal of Medicine (1955)

N-N′-N″-TRIETHYLENE thiophosphoramide is a sulfur derivative of triethylene phosphoramide, a polyfunctioning alkylating agent belonging to a group that includes nitrogen mustard and triethylene melamine. These compounds are related structurally and chemically as well as in their pharmacologic action in animals, especially on the hematopoietic system.Animal experiments with triethylene thiophosphoramide demonstrated its effectiveness in producing regression of Flexner—Jobling carcinoma on Sprague—Dawley rats1 and in the inhibition of the development of metastatic foci from rat mammary adenocarcinoma.2 Triethylene thiophosphoramide prolonged survival time in leukemic rats to the same degree as triethylene melamine, with the added advantage of less toxicity.3 The clinical . . .
Case 20-2015
Authors: Serguei Roumiantsev, Uzma Shah, Sjirk J. Westra, Joseph Misdraji
Journal: New England Journal of Medicine (2015)

A newborn girl was transferred to this hospital because of hypotension, coagulopathy, anemia, and hyperbilirubinemia. Generalized edema, anuria, and respiratory distress developed, and the trachea was intubated. Diagnostic procedures were performed.
OP0100-HPR Educational Needs Among Health Professionals Working with Systemic Sclerosis: An International Survey Conducted on Behalf of the Eular Scleroderma Health Professionals Network (EUSHNet)
Authors: L. M. Willems, A. C. Redmond, F. Braschi, T. A. Stamm, C. Boström, S. Decuman, A. Tyrrell Kennedy, J. Brozd, S. Roškar, V. Smith, C. H. van den Ende
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Due to the rarity and complexity of systemic sclerosis (SSc), expertise among health care providers on the available and effective treatment modalities for people with SSc is fragmented. The overarching aim of the EUSHNet project is to improve non-pharmacological care and reduce inequity through an international network of health professionals (HPs) working in SSc. <h3>Objectives</h3> To identify educational needs as perceived by European HPs working with people with SSc. <h3>Methods</h3> HPs working in SSc care across Europe were invited to complete an online survey through announcements by the EULAR HP newsletter, the FESCA website, EUSTAR centres, websites of national patient and HP associations, and by personal invitation. The survey asked HPs about received referrals, assessments and interventions used, current and future research projects, and perceived educational needs. <h3>Results</h3> In total, 60 HPs, from 14 different European countries and 7 different disciplines, completed the section of the questionnaire concerning educational needs. 87% of the HPs reported being experienced in clinical patient care or rehabilitation of people with SSc, and 28% had participated in post-graduate specialized training, education or course about SSc. Further, educational needs were reported by 59 (98%) HPs, and 20% reported that they were not sure whether their knowledge of current research evidence was up to date. A median of 6.5 areas of educational need were reported with further information about helping patients manage stiffness, pain, hand function, fatigue, and emotional problems cited as the most frequently mentioned areas (Table 1). The preferred mode of education delivery was reported to be a combination of internet/e-learning (73%), face-to-face sessions during conferences (62%), and written material (57%). Language barriers in the delivery of education were foreseen by about one third of the HPs in 10 countries. <h3>Conclusions</h3> Our results suggest that HPs would like to further develop their expertise regarding SSc care. To address these needs, educational courses and/or training should be developed and ways found to provide consistent education to all European HPs working in SSc. <h3>Disclosure of Interest</h3> None Declared
Abstract ADV09: Bladder cancer basics.
Authors: Vanessa Hoffman
Journal: Cancer Research (2013)

Abstract The Bladder Cancer Advocacy Network's (BCAN) mission is to increase public awareness about bladder cancer, to advance bladder cancer research, and to provide educational and support services for the bladder cancer community. BCAN works to serve over 520,000 bladder cancer survivors and 73,000 newly diagnosed patients each year in the United States. BCAN engages in many initiatives and programs. BCAN's current initiatives include the Women's Outreach Initiative and Veterans’ Outreach Initiative, which are engaging national task forces to raise awareness of bladder cancer among these constituencies. In patient education and support, BCAN's website: www/bacan.org- is one of the most comprehensive bladder cancer resources on the internet. BCAN also provides free bladder cancer patient education materials including patient tip sheets and a patient handbook-Bladder Cancer Basics for the Newly Diagnosed, which was revised this year and is now available in Spanish. BCAN offers Patient Insight Webinars throughout the year. BCAN also provides a free clinical trial matching service in coordination with Emerging Med, to help people obtain specific information about participating in bladder cancer research trials. BCAN staff answers patient calls and e-mails for more information, resources, and support. BCAN has facilitated the development of in-person bladder cancer support groups around the country and offers access to an online bladder cancer support community. BCAN also offers the Young Investigator Awards, announced this year, for three awards of $100,000 over two years, to increase the understanding of bladder cancer risk, biology, prevention, and treatment while encouraging young investigators to pursue a career in bladder cancer research. BCAN is also engaged in advocacy with staff members and volunteers serving on panels and participating in coalitions. BCAN has coordinated Walks for Bladder Cancer to raise awareness of the disease since 2011, on the first Saturday in May. In 2012, the Walks for Bladder Cancer held on May 5 took place in 60 communities, had more than 5,000 participants and raised more than $275,000. Citation Format: Vanessa Hoffman. Bladder cancer basics. [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 ADV09. doi:10.1158/1538-7445.AM2013-ADV09
SAT0259 Serum Levels of TOCILIZUMAB and Its Relationship with Disease Activity and Drug Dosage in Patients with Rheumatoid Arthritis
Authors: V. Ruiz-Esquide, A. González-Navarro, J. Yagüe, J. Ramírez, M.V. Hernández, S. Cabrera-Villalba, J. Inciarte-Mundo, J.D.D. Cañete, R. Sanmarti
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab (TCZ) is a humanized monoclonal antibody against interleukin-6 receptor used to treat active rheumatoid arthritis (RA). The response to treatment may depend on the serum levels achieved, which depend on the interval and the total dose administered. <h3>Objectives</h3> To analyze serum levels of TCZ and antidrug antibodies (ADA) in RA patients on chronic treatment with TCZ and evaluate their relationship with disease activity, serum levels of IL6 and CRP and drug dosage. <h3>Methods</h3> Cross-sectional study including all RA patients on chronic treatment with TCZ attended by our Arthritis Unit. Demographic data, disease activity, IL6, CRP, and TCZ (adequate = ≥5 ug/ml) serum levels and ADA (LISA TRACKER Tocilizumab LTT005 DuoDrug + ADAb) were collected. The dose and dose interval were correlated with clinical and serological parameters. <h3>Results</h3> 33 RA patients were included (91% female, age 53±12 years, disease duration 15.3±9.7 years, anti-CCP+ 66.7%, monotherapy 22.2%, DAS28 2.9±1.1). No patient had ADA. Serum TCZ levels were suboptimal (&lt;5 ug/ml) in 20 patients (60%), of whom 10 had non-detectable levels (&lt;1 ug/ml). Patients with adequate levels of TCZ had higher levels of IL6 and lower DAS28 and CRP than those with suboptimal levels (Table 1). 15 patients received a reduced dose of TCZ (4-6 mg/kg) due to persistent remission or low disease activity and these patients had serum levels of TCZ lower than patients on the standard dose, with no between-group differences in disease activity or CRP (Table 2). IL6 levels and TCZ serum levels were positively correlated (R2=0.268, p=0.005), but not DAS28 or CRP. In 3 patients, all with low disease activity, a curve of TCZ serum levels was made by TCZ dosage at baseline (before drug infusion) and 10, 20 and 28 days thereafter. In two patients, TCZ serum levels were not detectable by day 20. The third patient showed adequate levels throughout. <h3>Conclusions</h3> No ADA were found in RA patients treated with TCZ. Adequate levels of TCZ were associated with higher IL6 levels, lower DAS28 and, especially, lower CRP levels. More than 50% of patients had suboptimal or non-detectable drug levels, particularly those receiving a reduced TCZ dose, but most had achieved low disease activity or remission. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3536
Some cancer waits and pressure on elective waiting times are caused by lack of money, MPs hear
Authors: M. Limb
Journal: BMJ (2014)

The NHS will not collapse next year but its problems will get worse because of a lack of money, health economists have told MPs.

Experts from the King’s Fund, the Health Foundation, and the Nuffield Trust have warned of growing pessimism in health and social care about the effect of funding pressure on services. They gave evidence to the Commons health select committee on Tuesday 11 November as part of its inquiry into public spending on health and social care.

John Appleby, chief economist at the King’s Fund, said that it was especially worrying that financial problems were spreading beyond those NHS organisations that had a long history of them. A recent survey …
Severe Vitamin D Deficiency — Rickets
Authors: Thomas J Caruso, Gennadiy Fuzaylov
Journal: New England Journal of Medicine (2013)

A 12-year-old girl from Ukraine was hospitalized for evaluation of a history of long-bone fractures and failure to thrive. On initial presentation, she had hypocalcemia (calcium level, 6.7 mg per deciliter [1.7 mmol per liter]), a low 25-hydroxyvitamin D level (5 ng per milliliter [12 nmol per liter]), an elevated parathyroid hormone level (435 pg per milliliter), an elevated alkaline phosphatase level (546 U per liter), and a normal phosphorus level (4.1 mg per deciliter [1.3 mmol per liter]). These findings were consistent with vitamin D–deficient rickets. She also showed multiple sequelae of long-standing rickets, including costochondral swelling (rachitic rosary), . . .
Abstract 845: <i>In vitro</i> and <i>in vivo</i> pharmacology of SAR125844, a potent and selective intravenous MET kinase inhibitor undergoing Phase I clinical trial
Authors: Hélène Goulaouic, Mireille Kenigsberg, Christine Delaisi, Françoise Begassat, Véronique Do-Vale, Jessica Mestadier, Fabrice Bonche, Tsiala Bénard, Jean-Paul Nicolas, Loreley Calvet, Coumaran Egile, Conception Nemecek, Christoph Lengauer
Journal: Cancer Research (2012)

Abstract SAR125844 is a potent MET kinase inhibitor for intravenous (IV) administration, with nanomolar activity against the wild-type enzyme (IC50 = 4.2 nM) and some kinase domain mutants, such as M1250T and Y1235D. It is highly selective for MET kinase in a panel of 275 kinases tested, with only 5 other protein kinases inhibited at IC50 values below 300 nM. In cellular assays, SAR125844 inhibits MET autophosphorylation at the nanomolar range (IC50 from 1.4 to 5.1 nM), translating into antiproliferative activity selectively in MET-driven cell lines such as MET-amplified cell lines, with IC50 values in the low nanomolar range and induction of apoptosis. SAR125844 induces a G1 block in the two MET-amplified tumor cell lines tested. Moreover, the compound is also able to inhibit HGF-induced cell migration in PC-3 prostate tumor cell line. In two MET-amplified human gastric tumor xenograft models tested, SNU-5 and Hs 746T, SAR125844 intravenous treatment leads to potent impact on the MET signaling pathway in a dose and time dependent manner, with potent inhibition of MET autophosphorylation, as well as a significant effect on downstream PI3K/AKT and RAS/MAPK pathways. As a single agent, this translates into a dose-dependent antitumor activity in these two xenograft models, with tumor stasis at the lowest active dose and tumor regression at the highly active doses. High loading single dose administration of SAR125844 using a nanosuspension formulation allowed a sustained P-MET inhibition in tumors up to 7 days. In all models, antitumor activity was achieved at well tolerated doses without significant effect on body weight. The observed correlation between P-MET inhibition in the tumor and antitumor activity in preclinical settings suggests that P-MET evaluation in tumor biopsies could be a direct pharmacodynamic biomarker of SAR125844 activity in patients. In order to investigate whether a non-invasive biomarker could also be used as pharmacodynamic read-out, we measured shed-MET (soluble extracellular domain of the MET receptor) in the plasma of tumor-bearing mice and showed that its level correlates with tumor burden in 2 MET-amplified xenograft models. 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 845. doi:1538-7445.AM2012-845