tbuckley/cabot-search huggingface dataset:
Sun Exposure in History
Authors: Adam S. Aldahan, Vidhi V. Shah, Stephanie Mlacker, Keyvan Nouri
Journal: JAMA Dermatology (2016)

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Echocardiographic (Echo) monitoring of myocardial injury during doxorubicin (DOX) therapy for childhood acute lymphoblastic leukemia (ALL)
Authors: S. E. Lipshultz, N. Rifai, V. M. Dalton, D. E. Levy, L. B. Silverman, S. R. Lipsitz, S. D. Colan, R. D. Gelber, S. E. Sallan
Journal: Journal of Clinical Oncology (2004)

8505 Background: Myocardial injury echo monitoring is recommended during DOX. We examined the relationship between echo-determined left ventricular (LV) function & structure & serum cardiac troponin T (cTnT), a sensitive & specific measure of myocardial injury during DOX and continuation therapy for ALL. Methods: 206 high-risk ALL pts were randomized on DFCI protocol 95–001 to receive DOX alone (30 mg/m2/dose, n=101 pts, 300 mg/m2 cumulative dose), or dexrazoxane (DEX) (300 mg/m2) followed by DOX (n=105 pts). cTnT was assayed before, during, & after DOX in 76 DOX-only pts & 82 DEX-DOX pts with 2377 samples (mean-15.1 samples/pt). Pts with cTnT had 462 echos (median-2.5 echos/pt) while receiving (n=162) or at 198 days (median) after DOX (n=164, during continuation). Echo z-scores (standard deviations Â± the predicted value) of LV function (fractional shortening [FS] & contractility) & structure (end-diastolic diameter) were determined. In this substudy the echo & cTnT results were compared. Results: Elevations of cTnT (>0.01 ng/mL) occurred in 35% (55/158) of pts. Pts treated with DOX alone were significantly more likely to have elevated cTnT samples (50 vs 21%; P<0.001). Echos prior to DOX showed normal LV FS (n=84, mean z-score, 0.19, P=0.51) & contractility (n=22, mean z-score, -0.02, P=0.96); but slight LV dilation (n=79, dimension z-score, 0.28, P=0.03). After DOX, FS (n=91, mean z-score, -1.06, P<0.0001) & contractility (n=29, mean z-score, −0.82, P=0.02) were depressed & dimension was normal (n=89, mean z-score, 0.01, P=0.92). However, there were no significant differences between the DOX-alone & DEX-DOX pts for mean LV dimension, FS, or contractility before, during, or after DOX. FS was significantly depressed in both treatment groups during & after DOX. Conclusion: Echo-determined LV structure & function during therapy for ALL may not accurately assess myocardial injury measured by cTnT. The role of echo monitoring during therapy requires further study. Transient confounders (e.g., cytokine-mediated myocardial depressant substances) may misrepresent DOX-associated myocardial injury. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron NCI; Pharmacia-Upjohn, Inc.; Roche Diagnostocs Corp.
Effects of remote monitoring on clinical outcomes and use of healthcare resources in heart failure patients with biventricular defibrillators: results of the MORE‐CARE multicentre randomized controlled trial
Authors: Giuseppe Boriani, Antoine Da Costa, Aurelio Quesada, Renato Pietro Ricci, Stefano Favale, Gabriele Boscolo, Nicolas Clementy, Valentina Amori, Lorenza Mangoni di S. Stefano, Haran Burri
Journal: European Journal of Heart Failure (2016)
Comparison of Patient-Reported Outcomes in 5-Year Survivors Who Received Bone Marrow vs Peripheral Blood Unrelated Donor Transplantation
Authors: Stephanie J. Lee, Brent Logan, Peter Westervelt, Corey Cutler, Ann Woolfrey, Shakila P. Khan, Edmund K. Waller, Richard T. Maziarz, Juan Wu, Bronwen E. Shaw, Dennis Confer, Mary M. Horowitz, Claudio Anasetti
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Bone marrow or peripheral blood from unrelated donors may be used for hematopoietic cell transplantation. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them. <h3>Objective</h3> To compare patient-reported outcomes between patients randomized to receive 1 of 2 graft types for unrelated donor transplantation. <h3>Design, Setting, and Participants</h3> This follow-up of a randomized clinical trial included English- or Spanish-speaking patients 16 years or older participating in a multicenter randomized clinical trial of unrelated donor bone marrow (BM) vs peripheral blood (PB) (N = 551) in hematopoietic cell transplantation for hematologic neoplasms. Patient-reported outcomes were collected from patients at enrollment and 0.5, 1, 2, and 5 years after transplantation. <h3>Interventions</h3> Unrelated donor BM or PB hematopoietic cell transplantation. <h3>Main Outcomes and Measures</h3> Functional Assessment of Cancer Therapy–Bone Marrow Transplant, Mental Health Inventory, occupational functioning, Lee Chronic Graft-vs-Host Disease Symptom Scale. <h3>Results</h3> At 5 years after transplantation, 102 BM and 93 PB participants were alive and eligible for assessment (age ≥40 years or older: 104 [53.5%] male: 101 [51.8%]). The mean (SE) Mental Health Inventory Psychological Well-Being scores (78.9 [1.7] vs 72.2 [1.9];<i>P</i> = .01; higher better) and Lee chronic graft-vs-host disease symptom scores (13.1 [1.5] vs 19.3 [1.6];<i>P</i> = .004; lower better) were significantly better for BM recipients, adjusting for baseline scores and missing data. Recipients of BM were also more likely to be working full or part-time than recipients of PB (odds ratio, 1.5; 95% CI, 1.2-2.0;<i>P</i> = .002), adjusting for work status before transplantation. With a median follow-up of 73 months (range, 30-121 months) for survivors, no differences in survival (40% vs 39%;<i>P</i> = .84), relapse (32% vs 29%;<i>P</i> = .47), or treatment-related mortality (29% vs 32%;<i>P</i> = .44) between BM and PB were observed. <h3>Conclusions and Relevance</h3> Recipients of unrelated donor BM had better psychological well-being, less burdensome chronic GVHD symptoms, and were more likely to return to work than recipients of PB at 5 years after transplantation. Bone marrow should be the standard of care for these types of transplant procedures. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00075816
Abstract 3448: Cardiac Dystrophinopathies: Prevalence and Clinical Phenotypes in a Consecutive Series of 408 Males with Idiopathic Dilated Cardiomyopathy
Authors: Michele Pasotti, Alessandra Serio, Marta Diegoli, Fabiana Gambarin, Nicola Marziliano, Maurizia Grasso, Emanuele Porcu, Eliana Disabella, Carlo Campana, Stefano Ghio, Laura Scelsi, Mario Vigano, Luigi Tavazzi, Eloisa Arbustini
Journal: Circulation (2008)

Dystrophin gene (DYS) defects cause three major clinical phenotypes: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy (DCM). In the cardiology ...
Peripheral Nerve Regeneration: Current Status and New Strategies Using Polymeric Materials
Authors: Ana C. Pinho, Ana C. Fonseca, Arménio C. Serra, José D. Santos, Jorge F. J. Coelho
Journal: Advanced Healthcare Materials (2016)

Experiments concerning peripheral nerve regeneration have been reported since the end of the 19th century. The need to implement an effective surgical procedure in terms of functional recovery has resulted in the appearance of several approaches to solve this problem. Nerve autograft was the first approach studied and is still considered the gold standard. Since autografts require donor harvesting, other strategies involving the use of natural materials have also been studied. Nevertheless, the results were not very encouraging and attention has moved towards the use of nerve conduits made from polymers, whose properties can be easily tailored and which allow the nerve conduit to be easily processed into a variety of shapes and forms. Some of these materials are already approved by the US Food and Drug Administration (FDA), as is presented here. Furthermore, polymers with conductive properties have very recently been subject to intensive study in this field, since it is believed that such properties have a positive influence in the regeneration of the new axons. This manuscript intends to give a global view of the mechanisms involved in peripheral nerve regeneration and the main strategies used to recover motor and sensorial function of injured nerves.
Use Brexit to strengthen language tests for EU doctors, royal college says
Authors: Abi Rimmer
Journal: BMJ (2016)

The Royal College of Surgeons has called on the government to ensure that Brexit discussions permit the UK to strengthen language tests for doctors from the European Union (EU).

In a position statement, the college’s faculty of dental surgery (FDS) said that Britain’s decision to leave the EU created an opportunity for the government to strengthen the language tests that the General Medical Council (GMC) was allowed to apply to doctors from the European Economic Area (EEA).

“We would like to see the government ensure that any post-Brexit negotiations with the EU give the UK flexibility to test EEA applicants’ language skills in the same way as non-EEA applicants,” the FDS said.

The FDS said that data provided by the GMC following a Freedom of Information request showed that 29 doctors from the EEA …
Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock
Authors: Salomé L. Gazit, Boubacar Mariko, Patrice Thérond, Benoit Decouture, Yuquan Xiong, Ludovic Couty, Philippe Bonnin, Véronique Baudrie, Sylvain M. Le Gall, Blandine Dizier, Nesrine Zoghdani, Jessica Ransinan, Justin R. Hamilton, Pascale Gaussem, Pierre-Louis Tharaux, Jerold Chun, Shaun R. Coughlin, Christilla Bachelot-Loza, Timothy Hla, Benoit Ho-Tin-Noé, Eric Camerer
Journal: Circulation Research (2016)

Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The relative importance of S1P sources sustaining these processes remains unclear.To address the level of redundancy in bioactive S1P provision to the developing and mature vasculature.S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases -1 and -2. S1P deficiency impaired aggregation and spreading of washed platelets and profoundly reduced their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P deficiency aggravated vasoplegia in this model, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. Accordingly, the S1P2 receptor mediated most of the survival benefit of S1P, whereas the endothelial S1P1 receptor was dispensable for survival despite its importance for maintaining vascular integrity.Although source redundancy normally secures essential S1P signaling in developing and mature blood vessels, profound depletion of plasma S1P renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective during anaphylactic shock.
The Combination of PLX3397, a Selective FLT3-ITD Inhibitor, and Decitabine, a Hypomethylating Agent, Demonstrates Benefit in AML Cell Lines in Vitro and in Vivo
Authors: James Tsai, Elizabeth A Burton, Gaston Habets, Brian West, Paul Lin, Henry Hsu, Chao Zhang, Gideon Bollag
Journal: Blood (2014)
Phase II evaluation of nintedanib in the treatment of bevacizumab-resistant persistent/recurrent ovarian, fallopian tube, or primary peritoneal carcinoma.
Authors: Brittany Anne Davidson, Robert Squatrito, Linda R. Duska, Laura Jean Havrilesky, Nyssa Schwager, Michael McCollum, Sanja Arapovic, Angeles Alvarez Secord
Journal: Journal of Clinical Oncology (2016)

TPS5601 Background: Anti-angiogenic therapy with bevacizumab (B) has shown promise in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) however, the development of resistance against B-induced VEGF blockade may occur via secondary pathways. Data suggest that continued VEGF inhibition after progression may have utility in the management of B-treated patients. Nintedanib is a tyrosine kinase inhibitor that inhibits both the VEGF pathway & secondary pro-angiogenic pathways. In EOC, nintedanib has shown activity in the upfront setting when combined with standard chemotherapy. Methods: This is an open label multi-center study. The primary objective of this study is to assess the activity of nintedanib as measured by 6 month progression free survival (PFS) in patients with B-resistant, persistent/recurrent EOC, fallopian tube (FTC), or primary peritoneal carcinoma (PPC). Secondary objectives include tumor response based on RECIST 1.1 & Gynecologic Cancer Intergroup (GCIG) CA125 criteria, the frequency/severity of AE, & duration of PFS. Patient preferences for treatment outcomes & assessment of baseline quality of life (QOL) & cancer related symptoms will be performed. Translational objectives include evaluation of VEGF & growth factor levels to assess for correlation with outcomes as well as coagulation/endothelial cell activation markers that may predict treatment-related thrombotic/bleeding risk. Patients must have recurrent/persistent EOC, FTC or PPC with measurable/detectable disease and be B-resistant (treatment free interval after B response < 6 months or progression on B containing therapy) and have ≤ 3 prior cytotoxic regimens (including 1 platinum-based). Patients with prior radiation for non-EOC tumors, therapeutic anticoagulation, history of abdominal fistula/GI perforation, nonhealing ulcers, CNS disease or suspicion of transmural bowel involvement are excluded. Nintedanib is dosed at 200mg BID until progression or AE preclude therapy. Each cycle is 28 days. Blood/urine specimens are collected at pre-determined intervals. At this time, seventeen out of 27 patients planned for the first stage have been enrolled. Clinical trial information: NCT01669798.
The usefulness of PET/CT and diffusion-weighted MRI in pancreatic cancer.
Authors: M. Ueno, S. Ohkawa, T. Kawano, S. Kobayashi, K. Miyakawa, T. Yoshida
Journal: Journal of Clinical Oncology (2010)

e14651 Background: SUVs of FDG-PET are semi-quantitative and are affected by various factors (e.g., blood sugar, tumor diameter, examination time following FDG injection). Although SUVmax may be a prognostic factor, it is especially difficult to predict the survival of low-SUVmax patients from our previous study. On the other hand, in the diffusion-weighted MRI the apparent diffusion coefficient (ADC) is measured as an index. In this study, we examined the significance of SUV and ADC from the viewpoint of prognosis in pancreatic cancer. Methods: The subjects were 23 pancreatic cancer patients who underwent PET/CT and diffusion-weighted MRI. The acquisition time of PET/CT was 60 min after FDG injection and SUVmax were measured. Diffusion-weighted MRI was performed with a b-factor of 1,000 sec/mm2 and ADCmin was measured. The survival times were compared among the patients who were divided into two groups at median SUVmax and ADCmin using the Kaplan - Meyers and log-rank test. Results: The UICC stages were as follows: stage II; 4, stage III; 3, stage IV; 16. The therapeutic modalities were as follows: surgery; 4 patients, chemotherapy; 19 patients. SUVmax ranged from 3.33 to 11.33 with a median value of 8.33. ADCmin ranged from 0.50 to 1.46 with a median value of 0.81. The median survival time in all patients was 262 days. There was no correlation between SUVmax and ADCmin. Each patient in the high-SUVmax group and low-ADCmin group had a poor prognosis although it was not significant. Moreover when we divide the low-SUV max group into two groups by the value of ADCmin, low ADCmin patients in the low-SUVmax group had a poor prognosis (MST low 300, high 420 days, p = 0.07). Conclusions: Using ADC and SUV, we may predict the prognosis more precisely in pancreatic cancer patients. No significant financial relationships to disclose.
The anti-apoptotic effect of alpha-lipoic acid against neointimal hyperplasia via induction of Nur77-mediation.
Authors: J. Jeong, B. Kang, Y. Chae, J. Kim, I. Lee
Journal: Journal of Clinical Oncology (2010)

e13624 Background: Neointimal hyperplasia of vascular smooth muscle cells (VSMCs) is caused by increased proliferation and decreased apoptosis. We previously reported that alpha-lipoic acid (ALA), a naturally occurring antioxidant, prevents neointimal hyperplasia through its anti-inflammatory property. Nuclear receptor Nur77 (NR4A1; NGFI-B/TR3) induces apoptosis of various cancer cells and also inhibits VSMC proliferation. However, it is unknown whether Nur77-mediated apoptotic pathway is involved in the inhibitory effect of ALA on neointimal hyperplasia. We explored the hypothesis that ALA protects against neointimal hyperplasia through the induction of Nur77-mediated apoptosis in VSMCs. Methods: VSMCs were isolated from the thoracic aorta of 4-week-old male Sprague–Dawley (SD) rats and were treated with ALA (2 mmol/L). Results: ALA treatment induced VSMC apoptosis, as evidenced by increases in Bax expression, cytochrome c release and caspase-3 activation. Also, ALA enhanced the expression and cytoplasmic localization of Nur77, resulting in interaction of Nur77 with Bcl-2, which triggers Nur77-mediated apoptosis. siRNA-mediated downregulation of Nur77 diminished the pro-apoptotic effect of ALA on VSMCs. Moreover, ALA increased p38 MAPK phosphorylation and inhibition of p38 MAPK abolished ALA-induced apoptosis and cytoplasimc localization of Nur77. Adenovirus-mediated transfer of shRNA against Nur77 diminished inhibitory effect of ALA on neointimal hyperplasia. Conclusions: Collectively, these data indicate that ALA induced cell apoptosis through induction of p38 MAPK/Nur77-mediation. This study also suggests that stimulation of Nur77-mediated apoptotic pathway in VSMCs can be a potential therapeutic strategy to treatment of cancer. No significant financial relationships to disclose.
Gene Dosage of the Cell Cycle Regulatory Phosphatases Cdc25C and PP2A Determines Sensitivity to Lenalidomide in del(5q) MDS.
Authors: Sheng Wei, Kathy Rocha, Ann Williams, Xianhong Chen, P.K. Burnette, Julie Y. Djeu, Qing Liu, John Byrd, Lubomir Sokol, Nick Lawrence, Roberta Pireddu, Gordon Dewald, Jaroslaw Maciejewski, Alan List
Journal: Blood (2007)
Paracetamol is no more likely to exacerbate asthma in children than ibuprofen, shows study
Authors: Susan Mayor
Journal: BMJ (2016)

Using paracetamol to treat fever or pain is no more likely than ibuprofen to exacerbate asthma in children with mild persistent asthma, a randomised trial has shown.1

Observational data have previously linked paracetamol and asthma symptoms to decreased lung function, so some doctors have recommended avoiding the drug in children with asthma. But data from randomised trials have been limited.

The new study, reported in the New England Journal of Medicine …
Detection of Varicella Zoster Virus Specific CD8 T Cells in Patients after T Cell Depleted Allogeneic Stem Cell Transplantation by a Novel Epitope Screening Technology.
Authors: P.L.J. van der Heiden, M. Kester, M.W.A.G. van der Hoorn, W.M.E. Haarman, H.E. Barnby-Porritt, A. Banaszek, C.E. Napper, Erik W.A. Marijt, Roelof Willemze, J.H. Frederik Falkenburg, Mirjam Heemskerk
Journal: Blood (2007)
Vaccination Approaches for Retrovirus Infections1
Authors: Padman S. Sarma, Jack Gruber
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Vaccination Approaches for Retrovirus Infections Get access Padman S. Sarma, Padman S. Sarma Search for other works by this author on: Oxford Academic PubMed Google Scholar Jack Gruber Jack Gruber Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 769–774, https://doi.org/10.1093/jnci/76.4.769 Published: 01 April 1986
Maintenance therapy with avelumab (MSB0010718C; anti-PD-L1) vs continuation of first-line chemotherapy in patients with unresectable, locally advanced or metastatic gastric cancer: The phase 3 JAVELIN Gastric 100 trial.
Authors: Markus H. Moehler, Julien Taïeb, Jayne S. Gurtler, Huiling Xiong, Jenny Zhang, Jean-Marie Cuillerot, Narikazu Boku
Journal: Journal of Clinical Oncology (2016)

TPS4134 Background: Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers. Avelumab* is a fully human anti-PD-L1 IgG1 antibody that has shown promising efficacy and an acceptable safety profile in patients (pts) with adenocarcinoma of the stomach or gastroesophageal junction (AS/GEJ) treated in first-line (1L) and second-line settings. This open-label phase 3 study (NCT02625610) compares maintenance (Mn) treatment with single-agent avelumab vs continuation of 1L chemotherapy in pts with AS/GEJ. Methods: The primary objective of this global, multicenter trial is to demonstrate superiority of Mn therapy with avelumab vs continuation of 1L chemotherapy. Primary endpoint is overall survival or progression-free survival. Approximately 666 eligible pts will receive induction chemotherapy and upon completion, approximately 466 pts without disease progression will be randomized to receive treatment in the Mn phase. Main eligibility criteria include: histologically confirmed unresectable locally advanced or metastatic (LA/M) AS/GEJ, ECOG PS 0-1, no prior chemotherapy for LA/M disease, no prior therapy with any drug targeting T cell coregulatory proteins, and no concurrent anticancer treatment or immunosuppressive agents. Pts are not preselected for PD-L1 expression; HER2+ pts are excluded. During the induction phase, pts receive chemotherapy (oxaliplatin + 5-fluorouracil + leucovorin or oxaliplatin + capecitabine) for 12 wks. Pts entering the Mn phase are randomized to receive either avelumab 10 mg/kg as a 1h intravenous infusion Q2W or continuation of 1L chemotherapy. Treatment is given until disease progression, unacceptable toxicity, or consent withdrawal. Secondary endpoints include best overall response, quality of life (assessed via EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-STO22), safety as per NCI-CTCAE v4.03, and tumor biomarkers. Responses are evaluated according to RECIST 1.1 and adjudicated by a blinded independent review committee. Trial enrollment began in Dec 2015. *Proposed INN. Clinical trial information: NCT02625610.