tbuckley/cabot-search huggingface dataset:
Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study
Authors: Roxana Mehran, Usman Baber, Philippe Gabriel Steg, Cono Ariti, Giora Weisz, Bernhard Witzenbichler, Timothy D Henry, Annapoorna S Kini, Thomas Stuckey, David J Cohen, Peter B Berger, Ioannis Iakovou, George Dangas, Ron Waksman, David Antoniucci, Samantha Sartori, Mitchell W Krucoff, James B Hermiller, Fayaz Shawl, C Michael Gibson, Alaide Chieffo, Maria Alu, David J Moliterno, Antonio Colombo, Stuart Pocock
Journal: The Lancet (2013)
BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion
Authors: Hany Kayed, Sandor Bekasi, Shereen Keleg, Christoph W Michalski, Thomas Giese, Helmut Friess, Jörg Kleeff
Journal: Molecular Cancer (2007)

Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin) is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.
Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer
Authors: Andreas du Bois, Anne Floquet, Jae-Weon Kim, Joern Rau, Josep M. del Campo, Michael Friedlander, Sandro Pignata, Keiichi Fujiwara, Ignace Vergote, Nicoletta Colombo, Mansoor R. Mirza, Bradley J. Monk, Rainer Kimmig, Isabelle Ray-Coquard, Rongyu Zang, Ivan Diaz-Padilla, Klaus H. Baumann, Marie-Ange Mouret-Reynier, Jae-Hoon Kim, Christian Kurzeder, Anne Lesoin, Paul Vasey, Christian Marth, Ulrich Canzler, Giovanni Scambia, Muneaki Shimada, Paula Calvert, Eric Pujade-Lauraine, Byoung-Gie Kim, Thomas J. Herzog, Ionel Mitrica, Carmen Schade-Brittinger, Qiong Wang, Rocco Crescenzo, Philipp Harter
Journal: Journal of Clinical Oncology (2014)

Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy.Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators.Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%).Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697).
Lung cancer mortality at ages 35-54 in the European Union: ecological study of evolving tobacco epidemics
Authors: Joanna Didkowska, Marta Manczuk, Ann McNeill, John Powles, Witold Zatonski
Journal: BMJ (2005)

Epidemiological analyses indicate that disease attributable to smoking is a leading contributor to the large gap in premature mortality between the 15 countries that formerly made up the European Union and the new member states from central and eastern Europe.1 However, the prevalence of smoking in most countries has not been measured in a sufficiently consistent way, or over a long enough period, to be used to predict trends in diseases caused by smoking.

Lung cancer mortality can provide a useful measure of a population's exposure to smoking,2 3 especially the population segment aged 35-54, when around 80-90% of cases are caused by smoking. We used trends, for each sex, in age standardised mortality due to lung cancer for ages 35-54 to map the lagged effects of the smoking epidemic in the 15 original EU member states and new members from central and eastern Europe, and to …
Aminosalicylate as prophylaxis for Crohn's disease
Authors: A QASIM
Journal: Gut (2001)

Editor,—We read with interest the recent clinical @lert commentary by Rutgreerts ((2001) Gut 48:452–53; [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]) analysing the recently published study by Lochs and colleagues.1 Lochs et al concluded that compared with placebo, 18 months of treatment with high dose Pentasa (mesalazine 4 g/day) made no difference to postoperative recurrence rates in patients with Crohn's disease involving the small intestine and colon or colon alone (26.3% v 25.6% for mesalazine and placebo, respectively). We feel that the study raises many new questions with regards to the role of 5-aminosalicylate (5-ASA) formulations in the … [1]: {openurl}?query=rft.jtitle%253DGastroenterology%26rft.stitle%253DGastroenterology%26rft.aulast%253DLOCHS%26rft.auinit1%253DH.%26rft.volume%253D118%26rft.issue%253D2%26rft.spage%253D264%26rft.epage%253D273%26rft.atitle%253DProphylaxis%2Bof%2BPostoperative%2BRelapse%2Bin%2BCrohn%2527s%2BDisease%2BWith%2BMesalamine%253A%2BEuropean%2BCooperative%2BCrohn%2527s%2BDisease%2BStudy%2BVI%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0016-5085%252800%252970208-3%26rft_id%253Dinfo%253Apmid%252F10648454%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0016-5085(00)70208-3&link_type=DOI [3]: /lookup/external-ref?access_num=10648454&link_type=MED&atom=%2Fgutjnl%2F49%2F6%2F873.1.atom [4]: /lookup/external-ref?access_num=000084937900007&link_type=ISI
Magnetic resonance (MR) imaging of the chest: state-of-the-art
Authors: RC Bittner, R Felix
Journal: European Respiratory Journal (1998)

To date, magnetic resonance (MR) is established as an imaging modality in the diagnosis of chest diseases. Because of its excellent distinction of vessels and soft tissue, MR can be performed as the primary imaging procedure before computed tomography in patients with suspected vascular lesions, mediastinal masses, hilar lesions, and pathological changes of the pleura and the chest wall. In these cases, MR is able to provide all the necessary diagnostic information. In other patients, a limited number of MR images may be helpful in cases of equivocal or confusing CT or clinical findings. More detailed information can be obtained, using surface coils or special imaging sequences, i.e. high resolution MR images of the pleura or angiographic images of mediastinal and pulmonary vasculature. From a clinical viewpoint, the most important task for thoracic magnetic resonance nowadays is the pretherapeutic evaluation of intrathoracic masses, the differential diagnosis of benign versus malignant lesions, and the accurate documentation of tumour extent in malignancies including three-dimensional-display to improve surgical or radiation planning. Future directions in thoracic magnetic resonance will be predominantly influenced by postprocessing approaches, specialized imaging techniques, and magnetic resonance-guided interventional applications.
Identification of New Citrulline‐Specific Autoantibodies, Which Bind to Human Arthritic Cartilage, by Mass Spectrometric Analysis of Citrullinated Type II Collagen
Authors: Sabrina Haag, Nadine Schneider, Daniel E. Mason, Jonatan Tuncel, Ida E. Andersson, Eric C. Peters, Harald Burkhardt, Rikard Holmdahl
Journal: Arthritis & Rheumatology (2014)

To investigate type II collagen (CII) as a joint-specific target of the anti-citrullinated protein antibody (ACPA) response in rheumatoid arthritis (RA).Potential citrullinated neoepitopes were identified by high-resolution tandem mass spectrometry (MS/MS) of in vitro peptidylarginine deiminase 2 (PAD-2)-treated CII, and the relationship between citrullination and CII conformation was investigated by circular dichroism and conformation-dependent antibodies. Based on the MS analyses, synthetic peptides were designed and analyzed for serum IgG reactivity in the Epidemiological Investigation of RA (EIRA) case-control cohort of 1,949 RA patients and 278 healthy controls. Peptide-specific antibodies were purified from RA patient serum and used to stain RA cartilage specimens.We described the conformation-dependent citrullination pattern of CII after PAD-2 treatment at room temperature and 37°C and showed that CII could be citrullinated in its native triple-helical conformation. Screening of Arg and Cit pairs of synthetic peptides revealed new citrullinated B cell epitopes on CII. Antibodies directed to 2 proximal epitopes close to the C-terminus of the CII triple helix were recognized by autoantibodies in 21% and 17% of RA patients, respectively. Affinity-purified antibodies from RA sera directed to these 2 epitopes, but not antibodies directed to citrullinated α-enolase peptide 1, bound to RA cartilage.These findings suggest that cartilage-directed anticitrulline immunity contributes to the induction of joint inflammation in RA.
Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test
Authors: Manuel Zorzi, Ugo Fedeli, Elena Schievano, Emanuela Bovo, Stefano Guzzinati, Susanna Baracco, Chiara Fedato, Mario Saugo, Angelo Paolo Dei Tos
Journal: Gut (2014)

<h3>Objective</h3> Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. <h3>Design</h3> In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50–69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002–2004 (early screening areas (ESA)) and areas that introduced the screening in 2008–2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995–2007) and surgical resection rates (2001–2012). <h3>Results</h3> Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995–2000, 2006–2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006–2007 incidence) or dropped below initial values (surgery after 2007). <h3>Conclusions</h3> FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies.
A Model Educational Program for People With Type 2 Diabetes
Authors: Juan José Gagliardino, Graciela Etchegoyen
Journal: Diabetes Care (2001)

OBJECTIVE—To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical, biochemical, and therapeutic aspects as well as the economic cost of diabetes. RESEARCH DESIGN AND METHODS—Educators from each participating country were previously trained to implement the educational model. The patient population included 446 individuals with type 2 diabetes; all patients were &amp;lt;65 years of age, did not require insulin for metabolic control, did not have severe complications of diabetes or life-limiting illnesses, and had not previously participated in diabetes education courses. Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program (−6 months), on entry into the program (time 0), and at 4, 8, and 12 months after initiation of the program. RESULTS—All parameters measured had improved significantly (P &amp;lt; 0.001) by 1 year: fasting blood glucose (mean ± SD) 10.6 ± 3.5 vs. 8.7 ± 3.0 mmol/l; HbA1c 9.0 ± 2.0 vs. 7.8 ± 1.6%; body weight 84.6 ± 14.7 vs. 81.2 ± 15.2 kg; systolic blood pressure 149.6 ± 33.6 vs. 142.9 ± 18.8 mmHg; total cholesterol 6.1 ± 1.1 vs. 5.4 ± 1.0 mmol/l; and triglycerides 2.7 ± 1.8 vs. 2.1 ± 1.2 mmol/l. At 12 months, the decrease in pharmacotherapy required for control of diabetes, hypertension, and hyperlipidemia represented a 62% decrease in the annual cost of treatment ($107,939.99 vs. $41,106.30 [U.S.]). After deducting the additional cost of glucosuria monitoring ($30,604), there was still a 34% annual savings. CONCLUSIONS—The beneficial results of this educational model, implemented in 10 Latin American countries, reinforce the value of patient education as an essential part of diabetes care. They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease.
Phorbol ester increases the dihydropyridine-sensitive calcium conductance in a vascular smooth muscle cell line.
Authors: R D Fish, G Sperti, W S Colucci, D E Clapham
Journal: Circulation Research (1988)

In vascular smooth muscle, phorbol esters cause a slowly developing contraction and an associated transmembrane calcium flux, both of which are inhibited by dihydropyridine calcium channel antagonists. In the A7r5 cultured vascular cell line, we used the whole-cell voltage-clamp technique to identify voltage-dependent calcium conductances and investigate the effect of phorbol esters on that conductance having characteristic dihydropyridine sensitivity (slowly inactivating, high-threshold, "L-type"). With barium as the charge carrier, large-amplitude (100-800 pA) inward currents of two types were characterized by their kinetics and voltage dependence. With holding potential--80 mV, a rapidly inactivating, low-threshold current ("T-type") was activated by depolarizations above-40 mV and was maximal at -10 mV. With holding potential -30 mV, this component was inactivated, and a second slowly inactivating, high-threshold current was activated above -10 mV and was maximal at +10 to +20 mV. These currents are similar to the T-type and L-type currents previously described in vascular smooth muscle cells. When added to the bath, the active phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (100 nM) increased the slowly inactivating (L-type) current by 32 +/- 20% (n = 8, +/- SD). Phorbol-12,13-dibutyrate (100 nM) caused a similar effect, but the inactive phorbol, 4-alpha-phorbol (100 nM), did not. We conclude that at least two distinct calcium conductances are expressed in A7r5 vascular smooth muscle cells, and that the dihydropyridine-sensitive calcium conductance is acutely modulated by phorbol esters, presumably acting through stimulation of protein kinase C. Such modulation may play a role in increasing transmembrane calcium influx mediated by agonist-receptor interactions that lead to activation of protein kinase C and may help to sustain or amplify calcium-dependent cell responses.
Health problems in Iraq.
Authors: E. D. Acheson
Journal: BMJ (1992)

Iraq is faced with large scale public health problems that have been caused by the destruction to their infrastructure during the Gulf war. Humanitarian aid is needed in order to avoid a large scale human disaster. In 1988 73% of Iraq's population lived in urban areas. The loss of electrical generating capacity has affected hospitals, water purification and sewage treatment. Iraq had made great strides int he health of their people with an infant mortality rate of 42/1000 in 1990 and 52./1000 for children under 5. The international study team's survey of over 9000 households revealed surprising evidence of widespread chronic malnutrition. Based on accepted mortality as a baseline, data suggests that mortality among Iraqi infants and children under 5 doubled in 1991. The current food ration provides only half of the energy requirement and with rapidly accelerating inflation, the cost of food while only make the situation worse. The UN Disaster Relief Office has received $1.059 billion from donor countries; but, only half of the requested $14 million has been funded through Unicef. This money is needed to meet basic requirements for water, sanitation, antibiotics, and vaccines. The UN Security Council approved resolutions 706 and 712 which would have allowed Iraq to sell $1.6 billion for foodstuffs, medicines, and materials and supplies necessary to civilian needs subject to monitoring and supervision to ensure equitable distribution. The Iraqi government has not met the requirements of 706 and 712 because of the monitoring conditions, so no money has been issued. More money is needed if humanitarian organizations are to do their work. Only $29 million of the $145 million needed for the 1st half of this year has been pledged.
Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma
Authors: Carole Fakhry, Qiang Zhang, Phuc Felix Nguyen-Tan, David Rosenthal, Adel El-Naggar, Adam S. Garden, Denis Soulieres, Andy Trotti, Vilija Avizonis, John Andrew Ridge, Jonathan Harris, Quynh-Thu Le, Maura Gillison
Journal: Journal of Clinical Oncology (2014)

Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced.Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol.A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment.Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.
Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer
Authors: X.S. Chen, X.Q. Nie, C.M. Chen, J.Y. Wu, J. Wu, J.S. Lu, Z.M. Shao, Z.Z. Shen, K.W. Shen
Journal: Annals of Oncology (2010)
Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed
Authors: L B A van de Putte, C Atkins, M Malaise, J Sany, A S Russell, P L C M van Riel, L Settas, J W Bijlsma, S Todesco, M Dougados, P Nash, P Emery, N Walter, M Kaul, S Fischkoff, H Kupper
Journal: Annals of the Rheumatic Diseases (2004)

<h3>The study</h3> Herbert A, Rafiq M, Pham TM, et al. Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: a cohort study. <i>PLoS Med</i> 2021:18;e1003708. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combining-risks-cancer-and-ibd-allows-more-fast-track-referrals/
A PEROXIDASE-MEDIATED, <i>STREPTOCOCCUS MITIS</i>-DEPENDENT ANTIMICROBIAL SYSTEM IN SALIVA
Authors: Charles B. Hamon, Seymour J. Klebanoff
Journal: The Journal of Experimental Medicine (1973)

H(2)O(2) formation by Streptococcus mitis was measured by the catalase-dependent conversion of [(14)C]formate to (14)CO(2) ; it was optimal at pH 6.0-6.5 and required glucose. The H(2)O(2) formed by S. mitis could be employed as a component of an antimicrobial system that also included lactoperoxidase (LPO) and either iodide or thiocyanate ions in the concentrations present in saliva. The antimicrobial effect of the LPO-iodide-S. mitis system was measured by the decrease in the viable cell count of the target organisms (Escherichia coli, Staphylococcus aureus, Candida tropicalis). The antimicrobial effect of the LPO-thiocyanate-S. mitis system was measured by the decrease in the rate of growth or the rate of uptake of [(14)C]valine by the target organisms (E. coli, S. aureus). Mixed or parotid saliva could replace LPO and thiocyanate ions in the S. mitis-dependent inhibition of bacterial growth and valine uptake. The presence in saliva of a peroxidase-mediated, antimicrobial system dependent on microbial metabolism for H(2)O(2) and its role as a natural host defense mechanism are considered.
Acute Bleeding After Bone Marrow Transplantation (BMT)— Incidence and Effect on Survival. A Quantitative Analysis in 1,402 Patients
Authors: S. Nevo, V. Swan, C. Enger, K.J. Wojno, R. Bitton, M. Shabooti, A.K. Fuller, R.J. Jones, H.G. Braine, G.B. Vogelsang
Journal: Blood (1998)