tbuckley/cabot-search huggingface dataset:
<b>Unsafe and understudied: the US gun problem</b>
Authors: Margaret A Winker, Kamran Abbasi, Frederick P Rivara
Journal: BMJ (2016)

Overturn the funding freeze so we can restart a research effort barred by Congress in 1997

In recent weeks, the firearms controversy has again lit up the media in the United States, with clarification that anyone engaged in the business of selling firearms must get a license and conduct background checks.1 Although this clarification is a step in the right direction, we may never know its effects because of the continuing ban on federal funding of research into gun violence.

This ban and the subsequent stripping of research funding from the Centers for Disease Control and Prevention (CDC) was initiated after a study (coauthored by one of us) reported in 1993 that homes with guns were more likely to have a homicide by a family member or intimate partner than homes without guns.2 Congress, responding to pressure from the National Rifle Association (NRA), added the Dickey amendment to the Omnibus spending bill for 1997, which stated that “none of the funds … at the [CDC] may be used to advocate or promote gun control.”3 In 2011, Republicans in Congress added similar language to 2012 funding appropriations for the National Institutes of Health. This language has had a chilling effect on gun violence research to this day, despite pleas from many people, including Jay Dickey himself, to reverse Congress’s …
Early detection of recurrent breast cancer using metabolite profiling.
Authors: V. Asiago, L. Alvarado, N. Shanaiah, N. Gowda, K. Owusu-Sarfo, R. Ballas, D. Raftery
Journal: Journal of Clinical Oncology (2010)

1037 Background: The growing field of metabolite profiling (or metabolomics) focuses on the quantitative detection of multiple small molecules that provide tremendous information on biological status. In particular, detectable perturbations in the metabolite profile often result from pathophysiological stimuli, such as from cancer. We report on the development of metabolite profile for use as an early test for recurrent breast cancer. As is the case for early detection of primary breast cancer, it is anticipated that earlier recurrence diagnoses will not only improve survival but also help clinicians determine the best therapeutic strategies for patients by avoiding under or over treatment. Methods: We apply a combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) to analyze the metabolite profiles of 257 serial serum samples from breast cancer patients consisting 116 samples from breast cancer recurrence and 141 samples from breast cancer patients with no evidence of disease (NED). NMR and GC-MS data were analyzed by combining advanced univariate and multivariate statistical methods and comparison of individual spectral features between patients with and without recurrent breast cancer. Results: From multivariate analysis of 42 targeted metabolites, ten metabolite markers (7 from NMR and 3 from GC-MS) were used to build a regression model with high accuracy (AUROC >0.89 using 10 fold cross validation) with a sensitivity of 82% and specificity of 84% using a training set of samples. When the model was tested on an independent set of patient samples, it yielded a sensitivity of 76% and a specificity of 83% (AUROC >0.85). Strikingly, over 60% of the patients could be correctly predicted to have recurrence on average 10 months before clinical diagnosis, which represents a large improvement over the current diagnostic assays CA 27.29 and CA 15-3. To the best of our knowledge, this is the first study to develop and validate a prediction model for early detection of recurrent breast cancer based on metabolic profiles. Conclusions: The combination of NMR and MS provide a powerful approach for the development of metabolic profile-based diagnostic tests for detecting breast cancer recurrence. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Matrix-Bio Matrix-Bio Matrix-Bio Matrix-Bio
A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus docetaxel (D) and cisplatin (C) in patients (pts) with advanced solid tumors: preliminary results
Authors: G. Freyer Sr., P. Fumoleau, B. You, N. Isambert, P. Chevalier, V. Trillet Lenoir
Journal: Journal of Clinical Oncology (2008)

14539 Background: Aflibercept (AF), a potent inhibitor of vascular endothelial growth factor, is a recombinant fusion molecule of the human VEGF receptor R1 + R2 (Flt-1, KDR) extracellular domains and the Fc portion of human IgG1. AF binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. This study was designed to assess the safety, dose limiting toxicities (DLTs)/recommended dose (RD) and PK of AF + DC. Methods: This combination trial explored escalating iv doses of AF followed by fixed dose of D then C (each 75 mg/m2) every 3 weeks (q3w). Treatment cohorts consisted of at least 3 pts up to 6 pts in case of DLT. Results: 16 heavily pretreated pts (Male/Female 3/13, median age 55 [39–76], ECOG-PS 0/1: 9/7) were enrolled in 3 AF dose levels (4.0, 5.0 and 6.0 mg/kg). Pts’ cancers included breast (5), ovarian (5), colon (2) and others (4). Pts received a median number of 4 [2–8] treatment cycles (cy). DLTs were only hematological (febrile neutropenia at cy 1) for 1/6 pts at AF 4.0 mg/kg and 1/7 pts at AF 5.0 mg/kg. Following introduction of prophylactic G-CSF, no additional DLT was reported. The main AF-related Gr3–4 toxicity (% pts) was hypertension (13%). Moderate (Gr2) epistaxis (19%), proteinuria (17%), dysphonia (13%) were observed. Free and bound AF drug concentrations are comparable to those observed with AF as monotherapy. AF 6.0 mg/kg is the RD with D single-agent q3w in another parallel study and is also the RD with DC based on both the DLTs/safety profile and the PK of free AF in excess of bound AF at the end of the q3w dosing interval. One complete and 1 partial responses (both ovarian), 8 stable diseases were noted. Conclusions: AF + DC do not seem to major DC-related toxicities. AF 6 mg/kg combined with standard DC was selected and is being confirmed. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, sanofi-aventis Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, sanofi-aventis
First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer
Authors: V. Michalaki, C. Gennatas, S. Gennatas, J. Vasiliou, V. Smyrniotis
Journal: Journal of Clinical Oncology (2007)

14602 Background: The effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV in colorectal cancer treatment. The aim of this study was to evaluate efficacy and safety of the combination chemotherapy with irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal adenocarcinoma. Methods: Patients with advanced colorectal adenocarcinoma received a first-line chemotherapy with capecitabine (1000 mg/m2 twice daily) on days 1–14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Results: Twenty-eight patients were evaluable for response. Baseline characteristics: 18men, 10 women; median age 65.5 years (range, 49–73); colon cancer (71%), rectal cancer (29%). Most common metastatic sites were the liver (53.5%), lymph nodes (43%), lung (21%) and bones (18%). There were 7 partial responses (25%), 8 cases of stable disease (28.5%), and 13 cases of disease progression (46.5%). The median survival was 14 months (range, 2–28.8 months) and median progression-free survival was 7 months (range, 6- 26 months). The median number of cycles received was 7 (range, 3–15 cycles). Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. Conclusions: First-line capecitabine/ irinotecan is an active combination for the treatment of metastatic colorectal cancer achieving high efficacy with a good safety profile. No significant financial relationships to disclose.
Phase 1 Dose-Escalation/Expansion Study Of ARRY-614 In Patients With IPSS Low/Int-1 Risk Myelodysplastic Syndromes
Authors: Guillermo Garcia-Manero, Mikkael A. Sekeres, Alan F. List, H. Jean Khoury, Anjali Advani, Elias Jabbour, Hagop M Kantarjian, Jeffrey E Lancet, LouAnn Cable, Kari Guthrie, Grant Hogeland, Mieke Ptaszynski, Lara Maloney, Donald Corson, Rami S. Komrokji
Journal: Blood (2013)
Paclitaxel and cisplatin versus paclitaxel and cisplatin plus all-trans retinoic acid for the prevention of chemotherapy-induced neuropathy: A randomized phase II trial
Authors: M. A. Rios Trejo, T. Ceron Lizarraga, M. C. Fernández González, G. Ordoñez, L. Martinez Barrera, A. Astorga Ramos, D. Mendoza, J. Sotelo, O. Arrieta
Journal: Journal of Clinical Oncology (2009)

e14506 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event, similar to that of diabetes where there is reduction of the expression and transport of Neural Growth Factor (NGF). Retinoic acid regulates genes related to cellular proliferation and NGF expression. We conducted this clinical trial to determine the effect of all-trans retinoic acid (ATRA) on the development of CIPN with paclitaxel and cisplatin in patients with advanced non-small cell lung cancer (NSCLC). Methods: Ninety five patients with advanced NSCLC were included to receive chemotherapy based on paclitaxel 175 mg/m 2 and cisplatin 80 mg/m 2 every 3 weeks for a maximum of 6 cycles. The patients were randomized to receive ATRA 20 mg/day or placebo 1 week before treatment until after completing 2 cycles. Prior to chemotherapy and after 2 cycles of treatment neurophysiology tests, clinical exam and serum NGF levels (34 patients) were performed. Results: There were no differences in general characteristics of the patients between groups. NGF serum levels were lower in the placebo group 4.89 pg/ml baseline and 4.6 pg/ml 2C (p = 0.007) versus ATRA 4.8 pg/ml and 4.7 pg/ml (p=0.107). The electrophysiological studies showed a greater degree of motor axonal damage in the right (p=0.003) and left (p=0.013) tibial nerves in the placebo group after 2C. In the ATRA group there were no significant differences baseline and after chemotherapy. Conclusions: ATRA might have a neuroprotective effect in patients with NSCLC treated with paclitaxel and cisplatin. A phase III trial is needed to confirm these findings. No significant financial relationships to disclose.
Effect of impaired renal function on the outcome of submyeloablative allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies
Authors: J. Mehta, M. Cetiner, L. Gordon, A. Evens, M. Tallman, S. Williams, J. Winter, R. Meagher, S. Singhal
Journal: Journal of Clinical Oncology (2005)

6666 Background: Patients with abnormal renal function are generally excluded from conventional-intensity allogeneic HSCT because of the possibility of increased toxicity and transplant-related mortality (TRM). However, reduced-intensity allografts may be safer in the setting of kidney impairment although this has not been studied. Methods: The outcome of 63 consecutive submyeloablative allografts (27–66 years, median 52) performed for hematologic malignancies after 100 mg/m2 melphalan without (n=21; prior autograft) or with (n=42; no prior autograft) 50 mg/kg cyclophosphamide was analyzed to study the effect of pre-transplant glomerular filtration rate (GFR). GVHD prophylaxis comprised cyclosporine-mycophenolate (n=37; HLA-identical sibling donors) or tacrolimus-mycophenolate (n=26, 1-locus mismatched sibling or 9–10/10 allele-matched unrelated). No growth factors were administered post-transplant. Supportive care was uniform, and was independent of renal function. GFR (mL/min/1.73 m2) was calculated using the MDRD (Modification of Diet in Renal Disease) equation: 186 x (serum creatinine in mg/dL)−1.154 x (age in years)−0.203 x (0.742 if female) x (1.210 if African American). Results: Serum creatinine was 0.5–2.9 (median 0.9) mg/dL. GFR was 24–188 (median 88) mL/min/1.73 m2. 12 patients had mild-to-moderately impaired renal function with GFR ≤60 mL/min/1.73 m2. 14 patients experienced TRM; 3 of 12 with GFR ≤60 and 11 of 51 with GFR >60 (P=0.53). The cumulative incidence of relapse at 1 year was 50% and 46% in the two groups (P=0.23). The actuarial disease-free survival (DFS) at 1 year was 25% and 33% respectively (P=0.24), and the actuarial overall survival at 1 year was 42% and 46% respectively (P=0.20). GFR had no impact on TRM, relapse, DFS or OS when analyzed as a continuous variable. Conclusions: Renal function as measured by GFR does not affect the outcome of submyeloablative allogeneic HSCT. Patients with moderately compromised renal function should not be excluded from reduced-intensity allogeneic HSCT. Further work is required to define the safety of this procedure in patients with severely compromised renal function. No significant financial relationships to disclose.
Identification of four different metallo-β-lactamases, IMP-1, IMP-7, IMP-19 and VIM-2, in Japanese general hospitals
Authors: Naohiro Shibata, Hiroyuki Ohbayashi
Journal: European Respiratory Journal (2011)

Background: Metallo-β-lactamases (MBLs) are bacterial enzymes that hydrolyze carbapems. MBL-producing gram-negative bacilli have been emerging worldwide. In this study, different MBLs were identified in various lung diseases in the japanese clinical hospitals.  Methods: From Jan. 2009 to Dec. 2010, 1618 GNB strains were submitted to the laboratory of 6 general hospitals in Aichi prefecture. Strains demonstrating a high level ceftazidime resistance (MIC, >128 mg/ml) were subjected to a screening test for MBL production by using disks containing an MBL inhibitor, sodium mercaptoacetic acid (SMA). PCR and sequencing analyses were performed to confirm the types of MBLs and integrases using primers specific for each gene.  Results: Fifty-three strains (34 Pseudomonas aeruginosa, 11 P. putida and 8 Acinetobacter baumannii) were isolated from elderly patients in various wards. These strains were isolated from various respiratory specimens (sputum, pus). By PCR analyses, 35 IMP-1 producers (26 P. aeruginosa and 9 P. putida), 8 IMP-7 producers (8 P. aeruginosa), 4 VIM-2 producers (4 P. putida) and 8 IMP-19 producers (8 A. baumannii) were found. Three IMP-1 and 2 VIM-2 producers were isolated in the same hospital. All MBL genes identified in this study were mediated by class 1 integron.  Discussion: In this study, four different MBLs were identified in 6 general hospitals. This may owe to excessive use of broad-spectrum β-lactams including cephamycins and carbapenems. Thus, prudent use of antimicrobial agents with broad-spectrum and daily surveillance of multi-drug-resistant strains would be necessary to prevent further transmission of this kind of super microbes.
Introduction and Contents
Journal: JAMA (1964)

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Protease-activated receptor-4 deficiency does not protect against bleomycin-induced pulmonary fibrosis in mice: Figure 1–
Authors: Keren Borensztajn, JanWillem Duitman, Lois W. Brüggemann, C. Arnold Spek
Journal: European Respiratory Journal (2012)

Protease-activated receptor-4 deficiency does not protect against bleomycin-induced pulmonary fibrosis in mice Protease-activated receptor (PAR)-4 is a thrombin receptor expressed in lung tissue.Previous in vitro data showed that PAR-4 triggers epithelial-to-mesenchymal transition, which is crucial in pulmonary fibrosis.These observations prompted us to investigate the role of PAR-4 in a murine model of bleomycin induced pulmonary fibrosis.We observed that wildtype and PAR-4 deficient mice developed fibrosis, but there were no differences in the severity of fibrosis or in the expression of fibrotic markers like collagen and fibronectin in PAR-4 deficient mice compared with wildtype controls.Overall, our results demonstrate that PAR-4 does not play a significant role during pulmonary fibrosis and question the importance of PAR-4 in fibrotic disease.
Higher levels of thymidylate synthase gene expression are observed in pulmonary as compared with hepatic metastases of colorectal adenocarcinoma.
Authors: R Gorlick, R Metzger, K D Danenberg, D Salonga, J S Miles, G S Longo, J Fu, D Banerjee, D Klimstra, S Jhanwar, P V Danenberg, N Kemeny, J R Bertino
Journal: Journal of Clinical Oncology (1998)

PURPOSE It has been observed previously that the pulmonary metastases of colorectal adenocarcinoma are less responsive to therapy with fluorouracil (FUra) as compared with other sites of metastasis (liver, local). To investigate the basis of this chemoresistance, the levels of thymidylate synthase (TS) mRNA and protein were measured, as TS expression has been shown to be predictive of response to therapy in colorectal cancer. MATERIALS AND METHODS Tumors were obtained from 19 patients with metastatic colorectal cancer (12 hepatic and seven pulmonary). TS expression was measured by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and TS protein levels were measured by Western blotting. The presence of TS amplification was assessed by Southern blotting. Levels of p53 protein were determined using immunohistochemistry. RESULTS TS mRNA expression was shown to be significantly higher in the pulmonary metastases (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer. Lower TS expression was observed in patients with hepatic metastases who had received prior FUra versus patients who had not been treated. High levels of TS expression in some samples was associated with low-level (two to three gene copies) increases in TS gene copy numbers and this was observed more frequently in the pulmonary metastatic samples. The increased gene copy numbers occurred both in samples with wild-type p53 and those with mutant p53 tumor-suppressor gene as determined by immunohistochemistry. CONCLUSION High levels of TS enzyme may be the basis of the lack of response of pulmonary metastases to FUra treatment.
Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia
Authors: U Krug, W E Berdel, R P Gale, C Haferlach, S Schnittger, C Müller-Tidow, J Braess, K Spiekermann, P Staib, D Beelen, H Serve, C Schliemann, M Stelljes, L Balleisen, G Maschmeyer, A Grüneisen, H Eimermacher, A Giagounidis, H Rasche, R Hehlmann, E Lengfelder, E Thiel, A Reichle, C Aul, W-D Ludwig, W Kern, T Haferlach, W Köpcke, D Görlich, M C Sauerland, A Heinecke, B J Wörmann, W Hiddemann, T Büchner
Journal: Leukemia (2016)
COL2A1 gene polymorphisms and susceptibility to osteoarthritis of the hand in Finnish women
Authors: S Hamalainen, S Solovieva, A Hirvonen, T Vehmas, E-P Takala, H Riihimaki, P Leino-Arjas
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To study the role of two <i>COL2A1</i> single nucleotide polymorphisms (rs3737548 and rs2276455) and their haplotypes in individual susceptibility to osteoarthritis (OA) of the hand in Finnish women. <h3>Methods:</h3> Bilateral hand radiographs of 543 Finnish female dentists and teachers aged 45–63 years were examined and classified for the presence of OA by using reference images. The <i>COL2A1</i> genotypes were determined by PCR-based methods. Data regarding other risk factors were collected by questionnaire. The haplotypes were statistically reconstructed from the genotype data by the PHASE program. Associations between the genotypes/diplotypes and hand OA were studied by logistic regression. <h3>Results:</h3> Allowing for age and occupation, the carriage of at least one <i>COL2A1</i> intron 33 minor allele was associated with an increased risk of hand OA (odds ratio (OR) 1.58, 95% CI 1.05 to 2.36) and the number of affected joints. When stratified by occupation, the increased risk associated with the intron 33 minor allele carriage appeared to be mainly attributable to the dentists (OR 2.18, 95% CI 1.18 to 4.06). The 2-1 haplotype (exon 5B minor allele-intron 33 major allele) posed a significantly higher risk of hand OA (OR 3.21, 95% CI 1.08 to 9.55) compared with non-carriers. Moreover, an interaction was observed between intron 33 minor allele carriage and low task variation history in dental work (OR 2.87, 95% CI 1.05 to 7.89 for their joint effect). <h3>Conclusions:</h3> The results suggest that the studied <i>COL2A1</i> gene polymorphisms may play a role in the aetiology of hand OA and that this effect may be enhanced by repetitive loading work tasks.
Abstract 12388: Changes of Diastolic Function Following Anthraclycline-based Chemotherapy: A Prospective Study
Authors: Jose M Serrano, Rosa M Jimenez, Maria Luaces, Catherine Graupner, Pedro Talavera, Luis J Morales, Alejando Curcio, Iria Gonzalez, Carmen Cristobal, Juan A Guerra, Joaquin J Alonso
Journal: Circulation (2012)

Background: Chronic Anthracycline cardiotoxicity represents a major limitation for its use in cancer patients (Pts). Data about the incidence and evolution of diastolic dysfunction following anthra...