tbuckley/cabot-search huggingface dataset:
The PneuCarriage Project: A Multi-Centre Comparative Study to Identify the Best Serotyping Methods for Examining Pneumococcal Carriage in Vaccine Evaluation Studies
Authors: Catherine Satzke, Eileen M. Dunne, Barbara D. Porter, Keith P. Klugman, E. Kim Mulholland
Journal: PLoS Medicine (2015)

Background The pneumococcus is a diverse pathogen whose primary niche is the nasopharynx. Over 90 different serotypes exist, and nasopharyngeal carriage of multiple serotypes is common. Understanding pneumococcal carriage is essential for evaluating the impact of pneumococcal vaccines. Traditional serotyping methods are cumbersome and insufficient for detecting multiple serotype carriage, and there are few data comparing the new methods that have been developed over the past decade. We established the PneuCarriage project, a large, international multi-centre study dedicated to the identification of the best pneumococcal serotyping methods for carriage studies. Methods and Findings Reference sample sets were distributed to 15 research groups for blinded testing. Twenty pneumococcal serotyping methods were used to test 81 laboratory-prepared (spiked) samples. The five top-performing methods were used to test 260 nasopharyngeal (field) samples collected from children in six high-burden countries. Sensitivity and positive predictive value (PPV) were determined for the test methods and the reference method (traditional serotyping of >100 colonies from each sample). For the alternate serotyping methods, the overall sensitivity ranged from 1% to 99% (reference method 98%), and PPV from 8% to 100% (reference method 100%), when testing the spiked samples. Fifteen methods had ≥70% sensitivity to detect the dominant (major) serotype, whilst only eight methods had ≥70% sensitivity to detect minor serotypes. For the field samples, the overall sensitivity ranged from 74.2% to 95.8% (reference method 93.8%), and PPV from 82.2% to 96.4% (reference method 99.6%). The microarray had the highest sensitivity (95.8%) and high PPV (93.7%). The major limitation of this study is that not all of the available alternative serotyping methods were included. Conclusions Most methods were able to detect the dominant serotype in a sample, but many performed poorly in detecting the minor serotype populations. Microarray with a culture amplification step was the top-performing method. Results from this comprehensive evaluation will inform future vaccine evaluation and impact studies, particularly in low-income settings, where pneumococcal disease burden remains high.
Single dose of oral dexamethasone for outpatient croup
Authors: R. Helowicz, J. Walton
Journal: BMJ (1996)

Single dose of oral dexamethasone for outpatient croupFailure to follow up all patients is a concern EDrTOR,-G C Geelhoed and colleagues con- clude from their study that oral dexamethasone at a dose of 0.15 mg/kg is effective in reducing return to medical care in children with mild croup.'The sample size seems adequate, though on the borderline for detecting a 90% reduction,
Reduced Insulin Production Relieves Endoplasmic Reticulum Stress and Induces β Cell Proliferation
Authors: Marta Szabat, Melissa M. Page, Evgeniy Panzhinskiy, Søs Skovsø, Majid Mojibian, Juan Fernandez-Tajes, Jennifer E. Bruin, Michael J. Bround, Jason T.C. Lee, Eric E. Xu, Farnaz Taghizadeh, Shannon O’Dwyer, Martijn van de Bunt, Kyung-Mee Moon, Sunita Sinha, Jun Han, Yong Fan, Francis C. Lynn, Massimo Trucco, Christoph H. Borchers, Leonard J. Foster, Corey Nislow, Timothy J. Kieffer, James D. Johnson
Journal: Cell Metabolism (2015)
Granulocyte-Macrophage Colony-Stimulating Factor Upregulates Reduced 5-Lipoxygenase Metabolism in Peripheral Blood Monocytes and Neutrophils in Acquired Immunodeficiency Syndrome
Authors: Michael J. Coffey, Susan M. Phare, Sandro Cinti, Marc Peters-Golden, Powel H. Kazanjian
Journal: Blood (1999)
Labelling people as ‘High Risk’: A tyranny of eminence?
Authors: Teppo L N Järvinen
Journal: British Journal of Sports Medicine (2015)

Whenever a doctor cannot do good, he must be kept from doing harm.Hippocrates

Nowadays, being at ‘high risk’ of having a disease has become a disease in and of itself. Sweeping educational programmes at all levels of healthcare now turn an otherwise healthy person's ‘high’ blood pressure, elevated serum lipids or low bone density into chronic conditions having increased risk of a potentially bad event.1 But what represents ‘high risk’? This question lies at the heart of modern medicine, particularly with respect to pharmacological primary prevention.

Advocates of this evolution argue simply that primary prevention saves lives. However, permissive labelling of conditions as diseases may not be entirely harmless. On an individual patient level, possible disadvantages include making relatively healthy individuals perceive themselves as ‘sick’, and almost every treatment has inherent risks.2 On a societal level, we probably all still remember the discouraging effect of the new European guidelines on cardiovascular disease classified most adult Norwegians—among the healthiest populations in the world—to be at ‘high risk’ of cardiovascular disease.3 …
PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia
Authors: Christopher B. Cole, Angela M. Verdoni, Shamika Ketkar, Elizabeth R. Leight, David A. Russler-Germain, Tamara L. Lamprecht, Ryan T. Demeter, Vincent Magrini, Timothy J. Ley
Journal: Journal of Clinical Investigation (2015)

The DNA methyltransferases DNMT3A and DNMT3B are primarily responsible for de novo methylation of specific cytosine residues in CpG dinucleotides during mammalian development. While loss-of-function mutations in DNMT3A are highly recurrent in acute myeloid leukemia (AML), DNMT3A mutations are almost never found in AML patients with translocations that create oncogenic fusion genes such as PML-RARA, RUNX1-RUNX1T1, and MLL-AF9. Here, we explored how DNMT3A is involved in the function of these fusion genes. We used retroviral vectors to express PML-RARA, RUNX1-RUNX1T1, or MLL-AF9 in bone marrow cells derived from WT or DNMT3A-deficient mice. Additionally, we examined the phenotypes of hematopoietic cells from Ctsg-PML-RARA mice, which express PML-RARA in early hematopoietic progenitors and myeloid precursors, with or without DNMT3A. We determined that the methyltransferase activity of DNMT3A, but not DNMT3B, is required for aberrant PML-RARA-driven self-renewal ex vivo and that DNMT3A is dispensable for RUNX1-RUNX1T1- and MLL-AF9-driven self-renewal. Furthermore, both the PML-RARA-driven competitive transplantation advantage and development of acute promyelocytic leukemia (APL) required DNMT3A. Together, these findings suggest that PML-RARA requires DNMT3A to initiate APL in mice.
Induction (ICT) or consolidation chemotherapy (CT) with cisplatin (C) and paclitaxel (P) plus concurrent chemo-radiation (CT/TRT) with cisplatin and vinorelbine (V) for unresectable non-small cell lung cancer (NSCLC) patients (pts): Randomized phase II trial GFPC-GLOT-IFCT 02–01
Authors: P. Fournel, A. Vergnenégre, G. Robinet, H. Léna, R. Gervais, H. Le Caer, P. J. Souquet, J. M. Chavaillon, C. Chouaid, I. Martel-Lafay
Journal: Journal of Clinical Oncology (2006)

7048 Background: Concurrent CT/TRT is the standard treatment for unresectable stage III NSCLC, but the optimal sequencing of TRT and CT is not well defined.Consolidation CT with taxane seems to be a good approach (SWOG 95–04). Methods: Unresectable stage III NSCLC pts (weight loss &lt; 10%, ECOG PS 0–1, no supraclavicular lymph node or superior vena cava syndrome) were eligible. in Arm A, pts received 2 cycles of C 80 mg/m 2 and P 200 mg/m 2 followed by a concurrent CT/TRT including TRT as 66 Gy in 33 fractions and C 80 mg/m 2 d1,29 and 57 and V d1,8,29,36,57 and 64. In Arm B, the same CT/TRT began on d1 followed by 2 cycles of C and P. The primary objective was response rate at the end of treatment, assessed by RECIST criteria. 132 pts were needed. Results: From 05/2002 to 03/2005, 133 pts were included by 35 centers. 5 pts were ineligible. Both groups were well-matched for baseline characteristics. 30 pts were stage IIIAN2 and 98 stage IIIB. Toxicities (106 pts analyzable) grade 3–4 by CTC and RTOG criteria (Arm A/Arm B) were: neutropenia 36%/41%, infection 11%/15%, esophagitis 6%/13%, pneumonitis 0%/1%. 5 toxic deaths were observed (2 sepsis, 1 massive hemoptysis, 1 post-irradiation pneumonitis, 1 esophageal fistula). In Arm A, objective response rate was 36% after ICT. At the end of treatment, response rate (Arm A/Arm B) was in intent to treat: progression 19%/19%, stable-disease 6%/11%, objective response 55%/48%. 13 pts were not evaluable for response in Arm A and 14 in Arm B [ table ]. Conclusions: Toxicities and response rates are similar in both arms, but ICT followed by CT/TRT appears to provide a better therapeutic outcome. [Table: see text] No significant financial relationships to disclose.
Minimum unit pricing: better late than never
Authors: Mark Robinson, Gerry McCartney, Clare Beeston
Journal: BMJ (2015)

Now that the advocate general of the EU has given his opinion on minimum unit pricing, the case is expected to return to the Scottish courts, where the issue of whether the policy is “appropriate” and “superior to alternative measures such as increased taxation” will be further debated.1 We welcome this as an opportunity for new evidence to be considered. …
Molecular Mechanisms of Transmembrane Signaling in B Lymphocytes
Authors: J C Cambier, J T Ransom
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
The Efficacy of Cognitive-Behavioral Therapy and Psychodynamic Therapy in the Outpatient Treatment of Major Depression: A Randomized Clinical Trial
Authors: Ellen Driessen, Henricus L. Van, Frank J. Don, Jaap Peen, Simone Kool, Dieuwertje Westra, Mariëlle Hendriksen, Robert A. Schoevers, Pim Cuijpers, Jos W.R. Twisk, Jack J.M. Dekker
Journal: American Journal of Psychiatry (2013)

Objective The efficacy of psychodynamic therapies for depression remains open to debate because of a paucity of high-quality studies. The authors compared the efficacy of psychodynamic therapy with that of cognitive-behavioral therapy (CBT), hypothesizing nonsignificant differences and the noninferiority of psychodynamic therapy relative to CBT. Method A total of 341 adults who met DSM-IV criteria for a major depressive episode and had Hamilton Depression Rating Scale (HAM-D) scores ≥14 were randomly assigned to 16 sessions of individual manualized CBT or short-term psychodynamic supportive therapy. Severely depressed patients (HAM-D score >24) also received antidepressant medication according to protocol. The primary outcome measure was posttreatment remission rate (HAM-D score ≤7). Secondary outcome measures included mean posttreatment HAM-D score and patient-rated depression score and 1-year follow-up outcomes. Data were analyzed with generalized estimating equations and mixed-model analyses using intent-to-treat samples. Noninferiority margins were prespecified as an odds ratio of 0.49 for remission rates and a Cohen's d value of 0.30 for continuous outcome measures. Results No statistically significant treatment differences were found for any of the outcome measures. The average posttreatment remission rate was 22.7%. Noninferiority was shown for posttreatment HAM-D and patient-rated depression scores but could not be demonstrated for posttreatment remission rates or any of the follow-up measures. Conclusions The findings extend the evidence base of psychodynamic therapy for depression but also indicate that time-limited treatment is insufficient for a substantial number of patients encountered in psychiatric outpatient clinics.
Magnesium ion influx reduces neuroinflammation in Aβ precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin-1β
Authors: Pu Wang, Xin Yu, Pei-Pei Guan, Jing-Wen Guo, Yue Wang, Yan Zhang, Hang Zhao, Zhan-You Wang
Journal: Cellular and Molecular Immunology (2015)
British American Tobacco puts tobacco in new e-cigarette
Authors: Jonathan Gornall
Journal: BMJ (2015)

British American Tobacco (BAT) has announced plans for a hybrid product that combines electronic cigarette technology with tobacco.

Like a standard e-cigarette, the iFuse will heat nicotine infused liquid into a vapour, but this will then be passed through tobacco before being inhaled. BAT said that iFuse, a so called “heat not burn” product, will incorporate elements of its Kent brand of cigarettes and will be sold where that brand is popular. …
Surrogates for Survival or Other End Points in Oncology
Authors: Michael LeBlanc, Catherine Tangen
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Adipose tissue distribution is associated with glycaemic control and microalbuminuria in Chinese patients with type 2 diabetes: a cross-sectional study
Authors: Zhengyi Wang, Lin Ding, Yu Xu, Xiaolin Huang, Ying Chen, Lin Lin, Ya Huang, Po Wang, Kui Peng, Jieli Lu, Yuhong Chen, Min Xu, Weiqing Wang, Yufang Bi, Guang Ning
Journal: The Lancet (2015)
An Oncogenic <i>NTRK</i> Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101
Authors: Robert C. Doebele, Lara E. Davis, Aria Vaishnavi, Anh T. Le, Adriana Estrada-Bernal, Stephen Keysar, Antonio Jimeno, Marileila Varella-Garcia, Dara L. Aisner, Yali Li, Philip J. Stephens, Deborah Morosini, Brian B. Tuch, Michele Fernandes, Nisha Nanda, Jennifer A. Low
Journal: Cancer Discovery (2015)

Oncogenic TRK fusions induce cancer cell proliferation and engage critical cancer-related downstream signaling pathways. These TRK fusions occur rarely, but in a diverse spectrum of tumor histologies. LOXO-101 is an orally administered inhibitor of the TRK kinase and is highly selective only for the TRK family of receptors. Preclinical models of LOXO-101 using TRK-fusion-bearing human-derived cancer cell lines demonstrate inhibition of the fusion oncoprotein and cellular proliferation in vitro, and tumor growth in vivo. The tumor of a 41-year-old woman with soft-tissue sarcoma metastatic to the lung was found to harbor an LMNA-NTRK1 gene fusion encoding a functional LMNA-TRKA fusion oncoprotein as determined by an in situ proximity ligation assay. In a phase I study of LOXO-101 (ClinicalTrials.gov no. NCT02122913), this patient's tumors underwent rapid and substantial tumor regression, with an accompanying improvement in pulmonary dyspnea, oxygen saturation, and plasma tumor markers.TRK fusions have been deemed putative oncogenic drivers, but their clinical significance remained unclear. A patient with a metastatic soft-tissue sarcoma with an LMNA-NTRK1 fusion had rapid and substantial tumor regression with a novel, highly selective TRK inhibitor, LOXO-101, providing the first clinical evidence of benefit from inhibiting TRK fusions.
Integrating tumor microenvironment with cancer molecular classifications
Authors: Etienne Becht, Aurélien de Reyniès, Wolf H Fridman
Journal: Genome Medicine (2015)

The composition of the tumor microenvironment is associated with a patient's prognosis and can be therapeutically targeted. A link between the cellular composition and genomic features of the tumor and its response to immunotherapy is beginning to emerge. Analyzing the microenvironment of tumor molecular subgroups can be a useful approach to tailor immunotherapies.
Body Weight and Prognosis in Breast Cancer<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref><xref ref-type="fn" rid="FN4">4</xref>
Authors: N F Boyd, J E Campbell, T Germanson, D B Thomson, D J Sutherland, J W Meakin
Journal: JNCI Journal of the National Cancer Institute (1981)

We have examined the relationship between risk factors for breast cancer incidence and the subsequent prognosis of breast cancer among patients in a randomized controlled trial of adjuvant ovarian ablation. Body weight was the only risk factor found to be associated with statistically significant differences in survival. This finding could not be explained by a disproportionate number of anatomically more advanced tumors in the heavier women. In premenopausal women aged 45 years or more, the only group to benefit from adjuvant ovarian ablation, there was an interaction of treatment and weight, suggesting that weight exerts its influence on prognosis by a hormonal mechanism. The prognostic effect of weight was generally most marked in patients with tumors whose prognostic characteristics were favorable, and in these patients weight loss as an adjuvant treatment may reduce the frequency of disease recurrence.
Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis
Authors: G M Bell, A E Anderson, J Diboll, R Reece, O Eltherington, R A Harry, T Fouweather, C MacDonald, T Chadwick, E McColl, J Dunn, A M Dickinson, C M U Hilkens, John D Isaacs
Journal: Annals of the Rheumatic Diseases (2016)

Objectives To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. Methods An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×10 6 , 3×10 6 or 10×10 6 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. Results There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×10 6 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. Conclusion IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×10 6 tolDC but no systemic clinical or immunomodulatory effects were detectable. Trial registration number NCT01352858.
Local research ethics committees
Authors: H. Tunstall-Pedoe
Journal: BMJ (1995)

Local committees have strengths too

EDITOR,--Anyone familiar with observer variation in measurement, the psychology of committees, or lunacy in the law courts would predict disagreement between research ethics committees. K G M M Alberti implies that common forms, central direction, and training will help,1 but differences will remain. Is conformity the priority? If so, why have local committees?

The idea that research done in a community should be approved locally by a committee of medical and lay members is changing …
Abstracts from the Seventh Congress of the European Association for Neuro-Oncology
Journal: Neuro-Oncology (2006)

BACKGROUND: Conventional interpretation of methionine PET (Met-PET) scans in suspected brain tumors uses the ratio of the tracer uptake within the lesion to the corresponding contralateral area. The precise location at which the region of interest used to calculate the reference value is placed is vital, because local variations in methionine uptake may significantly alter the calculated ratio. Identifying a precise mirror region is complicated by the distorting effect of the tumor and the need for manual realignment of the image. METHOD: Patients with low-grade primary brain tumors or benignlesions were identified on the basis of a tissue diagnosis or surveillance neuroimaging that excluded a high-grade tumor. These conditions were selected because they primarily involve a single hemisphere, with methionine uptake in the unaffected hemisphere being essentially normal. A total of 180 Met-PET scans performed during 2003  2005 were identified from the database at the Max Planck Institute for Neurological Research, coded, and anonymized for analysis. Scans demonstrating midline lesions, significant mass effect, or evidence of substantial previous surgery were then excluded. A methionine template was prepared using data from patients who had undergone both FDG and Met-PET scans within eight weeks, with normalization to a previously developed FDG template. Methionine scans were coregistered to the template, after masking of any tumor, and the diseased hemispheres stripped. Mean uptake maps for each hemisphere were calculated on a voxel-by-voxel basis and merged to create the normal methionine uptake map. Scans unsuitable for inclusion into the normal map were reanalyzed using the contralateral hemisphere and the normal uptake map for reference values, allowing the methods to be compared. RESULTS: Good correlation was found between uptake ratios using reference values calculated by both methods. Reference values could be reliably calculated in tumors that were previously problematic to analyze, such as those that cross the midline. Coregistration of the normal map was impaired in some cases by loss of the normal architecture, but valid reference values were obtained despite this. CONCLUSION: Use of a normal uptake may facilitate calculation of PET uptake ratios in brain tumors. Further research is required to evaluate the correlation with histological findings and the accuracy of image coregistration in the presence of distorting tumors.
Mechanism of Action of Novel Marine Neurotoxins on Ion Channels
Authors: C H Wu, T Narahashi
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More