tbuckley/cabot-search huggingface dataset:
Establishment of Novel Preclinical Melanoma Models Resistant to Vemurafenib
Authors: C. Robichon, J.P. Annereau, B. Gomes, A. Pillon, L. de Vries, D. Cussac, N. Meyer, L. Lamant, A. Kruczynski, N. Guilbaud
Journal: Annals of Oncology (2013)
Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease
Authors: R. E Girgis, A. E Frost, N. S Hill, E. M Horn, D. Langleben, V. V McLaughlin, R. J Oudiz, I. M Robbins, J. R Seibold, S. Shapiro, V. F Tapson, R. J Barst
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Introduction:</h3> Endothelin receptor antagonism has become an important component in the treatment of pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). The purpose of this study was to analyse the safety and effectiveness of sitaxsentan, a selective antagonist of the ET<sub>A</sub> receptor, in a cohort of patients with PAH and CTD. Short-term clinical and haemodynamic effects and longer-term follow-up data are presented. <h3>Methods:</h3> A post hoc subgroup analysis was performed on 42 patients who had PAH associated with CTD, out of a group of 178 patients enrolled in a 12-week, double-blind, randomised clinical trial of sitaxsentan versus placebo. Data from 33 patients assigned to sitaxsentan 100 mg or 300 mg daily were pooled and compared with nine placebo-treated patients. There were 41 patients entered into the blinded extension study, in which all patients received either 100 mg or 300 mg sitaxsentan once daily. <h3>Results:</h3> Patients treated with sitaxsentan had a mean (SD) increase in 6 minute walk distance of 20 (5) m from baseline to week 12 (p = 0.037), whereas the placebo group had a decrease of 38 (84) m, resulting in a placebo-subtracted treatment effect of 58 m (p = 0.027). Parallel improvements in quality of life and haemodynamics were also observed. No patient discontinued their drug during the 12-week trial. In the blinded extension study (median treatment duration 26 weeks), more patients were in functional class I–II than in III–IV (p&lt;0.001) at the end of the study compared with the start of active therapy. Elevation of hepatic transaminase levels occurred in two patients. <h3>Conclusions:</h3> Sitaxsentan appears to be efficacious in patients with PAH associated with CTD.
Screening in GI Cancers: The Role of Genetics
Authors: Elena M. Stoffel
Journal: Journal of Clinical Oncology (2015)

Genetic and epigenetic alterations identified in tumors of different cancer types can provide insights regarding the roles played by different cell signaling pathways in carcinogenesis. Somatic mutation profiles of GI tumors are used to guide choice of chemotherapy and can facilitate identification of individuals whose cancers arise in the setting of genetic predisposition. This review provides a framework for how clinical history, family history of cancer, and tumor genomic phenotype can be used to screen patients with colorectal, gastric, or pancreatic cancer for hereditary cancer syndromes. Early identification of individuals who carry germline mutations can affect clinical care not only for patients with cancer but also for their at-risk relatives.
Lack of Lipotoxicity Effect on β-Cell Dysfunction in Ketosis-Prone Type 2 Diabetes
Authors: Guillermo E. Umpierrez, Dawn Smiley, Gonzalo Robalino, Limin Peng, Aidar R. Gosmanov, Abbas E. Kitabchi
Journal: Diabetes Care (2009)

OBJECTIVE Over half of newly diagnosed obese African Americans with diabetic ketoacidosis (DKA) discontinue insulin therapy and go through a period of near-normoglycemia remission. This subtype of diabetes is known as ketosis-prone type 2 diabetes (KPDM). RESEARCH DESIGN AND METHODS To investigate the role of lipotoxicity on β-cell function, eight obese African Americans with KPDM, eight obese subjects with type 2 diabetes with severe hyperglycemia without ketosis (ketosis-resistant type 2 diabetes), and nine nondiabetic obese control subjects underwent intravenous infusion of 20% intralipid at 40 ml/h for 48 h. β-Cell function was assessed by changes in insulin and C-peptide concentration during infusions and by changes in acute insulin response to arginine stimulation (AIRarg) before and after lipid infusion. RESULTS The mean time to discontinue insulin therapy was 11.0 ± 8.0 weeks in KPDM and 9.6 ± 2.2 weeks in ketosis-resistant type 2 diabetes (P = NS). At remission, KPDM and ketosis-resistant type 2 diabetes had similar glucose (94 ± 14 vs. 109 ± 20 mg/dl), A1C (5.7 ± 0.4 vs. 6.3 ± 1.1%), and baseline AIRarg response (34.8 ± 30 vs. 64 ± 69 μU/ml). P = NS despite a fourfold increase in free fatty acid (FFA) levels (0.4 ± 0.3 to 1.8 ± 1.1 mmol/l, P &amp;lt; 0.01) during the 48-h intralipid infusion; the response to AIRarg stimulation, as well as changes in insulin and C-peptide levels, were similar among obese patients with KPDM, patients with ketosis-resistant type 2 diabetes, and nondiabetic control subjects. CONCLUSIONS Near-normoglycemia remission in obese African American patients with KPDM and ketosis-resistant type 2 diabetes is associated with a remarkable recovery in basal and stimulated insulin secretion. A high FFA level by intralipid infusion for 48 h was not associated with β-cell decompensation (lipotoxicity) in KPDM patients.
Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease
Authors: Donald M. Lloyd-Jones, Kiang Liu, Lu Tian, Philip Greenland
Journal: Annals of Internal Medicine (2006)

Some experts propose C-reactive protein (CRP) as a screening tool for prediction of cardiovascular disease (CVD). Many epidemiologic studies show positive associations between elevated CRP levels and incident CVD. Assessment of the value of new prognostic tests, however, must rely on understanding of test characteristics rather than on associations measured by relative risks. In the case of CRP, test characteristics must be judged in the context of currently available CVD risk prediction algorithms. In this review of literature published before January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. They find no definitive evidence that, for most individuals, CRP adds substantial predictive value above that provided by risk estimation using traditional risk factors for CVD. Use of CRP may add to risk estimation in a limited subset of individuals who are at intermediate predicted risk according to the Framingham risk score. The authors propose that many questions still must be addressed before CRP is incorporated into risk prediction algorithms and before universal screening with CRP can be recommended.
Therapy Tolerance in Selected Patients With Androgen-Independent Prostate Cancer Following Strontium-89 Combined With Chemotherapy
Authors: Shi-Ming Tu, Jeri Kim, Lance C. Pagliaro, Funda Vakar-Lopez, Frankin C. Wong, Sijin Wen, Rosales General, Donald A. Podoloff, Sue-Hwa Lin, Christopher J. Logothetis
Journal: Journal of Clinical Oncology (2005)

Clinicians may have reservations about using strontium-89 for the treatment of bone metastases because of concerns that it may limit future use of chemotherapy. We assessed the rate of bone marrow failure in patients with prostate cancer who had received a dose of strontium-89.This subgroup analysis involved 34 patients with androgen-independent prostate cancer who had been given a dose of strontium-89 and six weekly doses of doxorubicin after response to induction chemotherapy. We assessed subsequent hematotoxicity in terms of bone marrow failure and the ability to tolerate additional treatments during a median of 25 months (range, 7 to 76 months) after the strontium-89 was administered.No patients developed bone marrow failure within 6 months of receiving strontium-89. Five (15%) of 34 patients developed bone marrow failure at a median 23 months (range, 6 to 53 months) after the strontium-89 treatment. Bone marrow biopsy performed in two of these five patients showed complete replacement of the marrow by tumor. Thirty-one patients (91%) received subsequent cytotoxic treatments at a median 11 months (range, 1 to 33 months) after the strontium-89 treatment.This analysis demonstrated that a single dose of strontium-89 combined with chemotherapy did not affect the delivery of subsequent courses of chemotherapy in a select group of patients. However, a majority of these therapies were given off protocol and were administered at a dose schedule that might be considered inappropriate or inadequate. The clinical role and safety profile of radiopharmaceuticals combined with chemotherapy in prostate cancer therapy deserve further exploration.
Unique among unique. Is it genetically determined?
Authors: M Gonzalez-Freire, C Santiago, Z Verde, J I Lao, J OIivan, F Gómez-Gallego, A Lucia
Journal: British Journal of Sports Medicine (2008)

The cross-country world championship is one of the best models to study characteristics needed to achieve top-level endurance athletic capacity. We report the genotype combination of a recent cross-country champion (12 km race) in polymorphisms of seven genes that are candidates to influence endurance phenotype traits ( ACTN3, ACE, PPARGC1A, AMPD1, CKMM, GDF8 (myostatin) and HFE ). His data were compared with those of eight other runners (world-class but not world champions). The only athlete with the genotype theoretically more suited to attaining world-class endurance running performance was the case study subject. A favourable genetic endowment, together with exceptional environmental factors (years of altitude living and training in this case), seems to be necessary to attain the highest possible level of running endurance performance.
Change in incidence of clinic visits for all-cause and rotavirus gastroenteritis in young children following the introduction of universal rotavirus vaccination in Israel
Authors: Khitam Muhsen, Gabriel Chodick, Sophy Goren, Emilia Anis, Tomer Ziv-Baran, Varda Shalev, Dani Cohen
Journal: Eurosurveillance (2015)

Both rotavirus vaccines RotaTeq and Rotarix were efficacious against severe rotavirus gastroenteritis in clinical trials; yet real-world data on the effect of rotavirus vaccines on mild to moderate disease are limited. We used a large computerised database of Maccabi Health Services Health Maintenance Organisation (HMO), the second largest HMO in Israel covering 25% of the Israeli population, to compare the incidence of acute gastroenteritis (AGE) clinic visits in community settings (n=302,445) before (2005-10) and after (2011-13) the introduction of universal rotavirus immunisation in Israel. We retrieved laboratory results of rotavirus antigen tests (n=18,133) and using a weighted analysis, we estimated the impact of rotavirus immunisation on the disease burden of rotavirus AGE clinic visits. Following the introduction of universal rotavirus immunisation, the typical winter peaks of rotavirus AGE were substantially lower and significant reductions of 14.8% (95% confidence interval (CI): 13.5-16.1) in all-cause AGE clinic visits and of 59.7% (95% CI: 59.8-62.6) in rotavirus AGE clinic visits were observed. The decrease was observed in all age groups, but it was greater in children aged 0 to 23 months than those aged 24 to 59 months. Continued rotavirus laboratory surveillance is warranted to monitor the sustainability of these changes.
Nature of Induced Persistent Vaginal Cornification in Mice. IV. Changes in the Vaginal Epithelium of Old Mice Treated Neonatally With Estradiol or Testosterone&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: T Kimura, S Nandi
Journal: JNCI Journal of the National Cancer Institute (1967)

BALB/cCrgl female mice were treated with different doses of estradiol or testosterone for the first 5 days of life. Some mice in each group were ovariectomized at 110–120 days of age, and all mice were killed at 15–17 months of age. Vaginas, uteri, ovaries, adrenals, and mammary glands were examined, and the long-term effects of neonatal steroid treatment on these organs are described. Hyperplastic epithelial lesions resembling epidermoid carcinomas were found in the vaginas of both intact and ovariectomized mice treated with either steroid at dose levels associated with the induction of ovary-independent persistent vaginal cornification, although ovariectomy reduced the incidence of such lesions. Vaginal lesions also occurred in intact mice with ovary-dependent persistent estrus, but not in ovariectomized mice from these groups that had been treated with low steroid doses. It was concluded that the development of hyperplastic changes in the vaginal epithelium depends on factors which also control the development of persistent cornification, though vaginal hyperplasia is more frequently an ovary-dependent phenomenon.
Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production
Authors: F. Lavie, C. Miceli-Richard, M. Ittah, J. Sellam, J.-E. Gottenberg, X. Mariette
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> The cytokine B cell-activating factor of the TNF family (BAFF) is involved in the pathogenesis of autoimmune diseases. <b>Objective:</b> To access changes in serum protein and mRNA levels of BAFF after rituximab treatment. <b>Methods:</b> Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients (two with lupus, two with Sjögren's syndrome, one with rheumatoid arthritis) before and 12 weeks (range 7–17) after a first course of rituximab infusion. Monocytes and B cells were selected from healthy controls and cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real-time PCR, respectively. <b>Results:</b> After rituximab treatment, median serum BAFF protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In monocytes cocultured with autologous B cells, BAFF protein level decreased, whereas the mRNA level was stable. In one closely monitored patient, the mRNA ratio of BAFF to actin in PBMCs increased later than the BAFF serum level. <b>Conclusions:</b> Two distinct mechanisms are probably involved in the increase in BAFF level after B cell depletion: (1) the decrease in its receptors leading to a release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could favour the re-emergence of autoreactive B cells.
Response to: Should we give long-term macrolide therapy for COPD?
Authors: Richard K Albert
Journal: Thorax (2013)

The letter submitted by Crosbie and Woodhead1 pertaining to our study of azithromycin for prevention of acute chronic obstructive pulmonary disease (COPD) exacerbations2 contains a number of errors and misconceptions.

First, Crosbie and Woodhead stated that our study was not double-blind. The complete protocol (published as an on-line supplement to the manuscript) indicated that ‘This is a prospective, randomised, double-blind, placebo-controlled trial…’.1 

Second, while Crosbie and Woodhead correctly note that …
The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer
Authors: Daniel W. Lee, David M. Barrett, Crystal Mackall, Rimas Orentas, Stephan A. Grupp
Journal: Clinical Cancer Research (2012)

Abstract Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor–based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, potential for expansion, and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. In pediatric oncology, CD19 and GD2 are compelling antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma, respectively, with this approach, but it is likely that other antigens expressed in a variety of childhood cancers will also soon be targeted using this therapy. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer. Clin Cancer Res; 18(10); 2780–90. ©2012 AACR.
Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL
Authors: Simona Soverini, Giovanni Martinelli, Sabrina Colarossi, Alessandra Gnani, Michela Rondoni, Fausto Castagnetti, Stefania Paolini, Gianantonio Rosti, Michele Baccarani
Journal: The Lancet Oncology (2007)
TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus
Authors: Wataru Matsuyama, Masuki Yamamoto, Ikkou Higashimoto, Ken-ichi Oonakahara, Masaki Watanabe, Kentarou Machida, Teizo Yoshimura, Nobutaka Eiraku, Masaharu Kawabata, Mitsuhiro Osame, Kimiyoshi Arimura
Journal: Blood (2004)
Identification and characterization of novel amphioxus microRNAs by Solexa sequencing
Authors: Xi Chen, Qibin Li, Jin Wang, Xing Guo, Xiangrui Jiang, Zhiji Ren, Chunyue Weng, Guoxun Sun, Xiuqiang Wang, Yaping Liu, Lijia Ma, Jun-Yuan Chen, Jun Wang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang
Journal: Genome biology (2009)

Abstract Background microRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. While the number of known human and murine miRNAs is continuously increasing, information regarding miRNAs from other species such as amphioxus remains limited. Results We combined Solexa sequencing with computational techniques to identify novel miRNAs in the amphioxus species B. belcheri (Gray). This approach allowed us to identify 113 amphioxus miRNA genes. Among them, 55 were conserved across species and encoded 45 non-redundant mature miRNAs, whereas 58 were amphioxus-specific and encoded 53 mature miRNAs. Validation of our results with microarray and stem-loop quantitative RT-PCR revealed that Solexa sequencing is a powerful tool for miRNA discovery. Analyzing the evolutionary history of amphioxus miRNAs, we found that amphioxus possesses many miRNAs unique to chordates and vertebrates, and these may thus represent key steps in the evolutionary progression from cephalochordates to vertebrates. We also found that amphioxus is more similar to vertebrates than are tunicates with respect to their miRNA phylogenetic histories. Conclusions Taken together, our results indicate that Solexa sequencing allows the successful discovery of novel miRNAs from amphioxus with high accuracy and efficiency. More importantly, our study provides an opportunity to decipher how the elaboration of the miRNA repertoire that occurred during chordate evolution contributed to the evolution of the vertebrate body plan.
Evidence-Based Deprescribing of Statins in Patients With Advanced Illness
Authors: Holly M. Holmes, Adam Todd
Journal: JAMA Internal Medicine (2015)

Several observational studies have demonstrated that statins continue to be prescribed for patients with limited life expectancy. In one study, 2 up to 62% of patients with cancer and a poor prognosis continued to receive statins, often for primary prevention of cardiovascular disease. In another trial, 3 the time to stopping treatment with a statin was similar in patients with cancer and in those without cancer, and more than 31% of patients with cancer filled a statin prescription within 30 days of death. Patients with other life-limiting illness, such as advanced dementia, also continued to receive statins even at the end of life. 4 Why are statins continued until the end of life? This is a complex multifaceted issue. Stopping statin therapy in the case of limited life expectancy has been advocated as a relatively straightforward decision; a recommendation of the Choosing Wisely campaign advises not to start lipid-lowering medications in patients with limited life expectancy. 5 However, at present, little is known about the barriers faced by clinicians when stopping statin treatment in patients with limited life expectancy. There may be continued uncertainty on the part of clinicians about the benefits afforded by continuing the treatment, particularly if a patient has been receiving the medication for a long time without adverse effects. Furthermore, clinicians and patients may be uncertain about the benefits and harms of discontinuing the therapy. In this issue of JAMA Internal Medicine, Kutner and colleagues 1 present the results of its first multicenter study: a pragmatic randomized trial of statin therapy discontinuation in patients with advanced disease and limited prognosis. This study suggests that stopping statin treatment at the end of life may be safe and is potentially associated with improved quality of life and reduced cost. The importance of these results cannot be overstated; clinicians wishing to recommend discontinuing the treatment in patients with advanced disease and limited life expectancy now have an evidence base to inform their decision making. Indeed, patients and their caregivers can now be advised that both withdrawing and continuing statin therapy are reasonable alternatives in advanced illness and in the absence of recent cardiovascular events. Will this study provide the evidence needed to help clinicians deprescribe statin treatment? Kutner et al 1 suggest that
Distribution of HLA histocompatibility antigens, ABO blood groups and Rh antigens in alcoholic liver disease.
Authors: M Melendez, L Vargas-Tank, C Fuentes, R Armas-Merino, D Castillo, C Wolff, M E Wegmann, J Soto
Journal: Gut (1979)

The distribution of 16 antigens of the HLA-A and 15 antigens of the HLA-B series of HLA system, the blood groups ABO, and Rh antigens were studied in 40 alcoholics with cirrhosis, 18 alcoholics without cirrhosis, and in normal control subjects. The group of alcoholics with cirrhosis showed a significantly high frequency of HLA-B13 (corrected P less than 0.01) when compared with normal subjects, while the frequency of HLA-B13 was similar to normal in alcoholics without cirrhosis. On the basis of these findings, its seems that the carriers of HLA-B13 are more susceptible to liver damage caused by alcohol. Both groups of alcoholics and the normal controls had a similar distribution of ABO blood groups and Rh antigens.