tbuckley/cabot-search huggingface dataset:
Standards for control may not be consistent across United Kingdom
Authors: P. Ormerod
Journal: BMJ (1996)

<h3>Background</h3> Antiphospholipid antibodies in SLE may be affected by disease activity and treatment, but past studies have been conflicting. We investigated the association of titers of antiphospholipid antibodies with disease activity and therapy. <h3>Methods</h3> 943 SLE patients, who had at least 10 quarterly visits for testing for each anticardiolipin isotype (IgG, IgM and IgA) and dRVVT, were included in the study. Disease activity was measured with both the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Physician Global Assessment (PGA). Treatment was recorded at every visit. Results aCL IgG &gt;40 and aCL IgA were not associated with disease activity. Hydroxychloroquine reduced the levels of all antibodies, except for IgA aCL. Prednisone reduced aCL IgG but not aCL IgM, aCL IgA &gt;40 or dRVVT (seconds prolongation). <h3>Conclusion</h3> High titer aCL were not affected by disease activity. Thus these patients are more like ‘primary’ antiphospholipid patients. Hydroxychloroquine use was associated with reduced lupus anticoagulant (by seconds of prolongation) and reduced titers for most of the isotypes of anticardiolipin. Prednisone did not reduce the seconds of dRVVT prolongation. Anticardiolipin IgA seemed the most resistant to therapy.
Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation
Authors: C.-F. Fang, M.-J. Ma, B.-D. Zhan, S.-M. Lai, Y. Hu, X.-X. Yang, J. Li, G.-P. Cao, J.-J. Zhou, J.-M. Zhang, S.-Q. Wang, X.-L. Hu, Y.-J. Li, X.-X. Wang, W. Cheng, H.-W. Yao, X.-L. Li, H.-M. Yi, W.-D. Xu, J.-F. Jiang, G. C. Gray, L.-Q. Fang, E.-F. Chen, W.-C. Cao
Journal: BMJ (2015)

<b>Study question</b> Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? <b>Methods</b> An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. <b>Study answer and limitations</b> A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. <b>What this study adds</b> Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live poultry markets should be enhanced to monitor transmissibility and pathogenicity of the virus. <b>Funding, competing interests, data sharing</b> Funding support from the Program of International Science and Technology Cooperation of China (2013DFA30800), Basic Work on Special Program for Science and Technology Research (2013FY114600), National Natural Science Foundation of China (81402730), Special Program for Prevention and Control of Infectious Diseases in China (2013ZX10004218), US National Institutes of Health (1R01-AI108993), Zhejiang Province Major Science and Technology Program (2014C03039), and Quzhou Science and Technology Program (20111084). The authors declare no other interests and have no additional data.
Increasing Volume and Changing Characteristics of Invasive Pulmonary Aspergillosis on Sequential Thoracic Computed Tomography Scans in Patients With Neutropenia
Authors: Denis Caillot, Jean-Francois Couaillier, Alain Bernard, Olivier Casasnovas, David W. Denning, Lionel Mannone, Jose Lopez, Gerard Couillault, Francoise Piard, Odile Vagner, Henri Guy
Journal: Journal of Clinical Oncology (2001)

PURPOSE: In patients with neutropenia, thoracic computed tomography (CT) halo and air-crescent signs are recognized as major indicators of invasive pulmonary aspergillosis (IPA). Nevertheless, the exact timing of CT images is not well known. PATIENTS AND METHODS: Seventy-one thoracic CT scans were analyzed in 25 patients with neutropenia with surgically proven IPA. RESULTS: On the first day of IPA diagnosis with early CT scan (d0), a typical CT halo sign was observed in 24 of 25 patients. At that time, the median number of thoracic lesions was two (range, one to six), and pulmonary involvement was bilateral in 12 cases. The halo sign was present in 68%, 22%, and 19% of cases on d3, d7, and d14, respectively. Similarly, the air-crescent sign was seen in 8%, 28%, and 63% of cases on the same days. Otherwise, a nonspecific air-space consolidation aspect was seen in 31%, 50%, and 18% of cases on the same days. The analysis of calculated aspergillary volumes on CT showed that, despite antifungal treatment, the median volume of lesions increased four-fold from d0 to d7, whereas it remained stable from d7 to d14. Overall, 21 patients (84%) were cured by the medical-surgical approach. CONCLUSION: In patients with neutropenia, CT halo sign is a highly effective modality for IPA diagnosis. The duration of the halo sign is short, and it demonstrates the value of early CT. The increase of the aspergillosis size on CT in the first days after IPA diagnosis is not correlated with a pejorative immediate outcome when using a combined medical-surgical approach.
Tetramer based approach for efficient identification and isolation of neo-antigen specific CD8 T cells from peripheral blood (PBL) of patients with metastatic cancers
Authors: Mini Bharathan, Katarina Trebska-McGowan, Pasetto Anna, Drew C Deniger, Ken-ichi Hanada, Jared J Gartner, James C Yang, Steven A Rosenberg, Paul F Robbins
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive cell therapy with T cells bearing mutation specific T cell receptors (TCR) can be an effective method for treating metastatic cancers. The objective of this study was to identify mutation reactive T cells in the circulation of patients with different types of metastatic
“Gunslinger’s gait”: a new cause of unilaterally reduced arm swing
Authors: Rui Araújo, Joaquim J Ferreira, Angelo Antonini, Bastiaan R Bloem
Journal: BMJ (2015)

<b>Objective</b>&nbsp;To postulate a new possible cause of a unilaterally reduced arm swing in addition to the known medical conditions such as shoulder pathology, Erb’s palsy, stroke, and Parkinson’s disease. <b>Methods</b>&nbsp;Analysis of YouTube videos depicting the gait of highly ranked Russian officials. <b>Results</b>&nbsp;We found a similar walking pattern in President Vladimir Putin, Prime Minister Dmitry Medvedev and three other highly ranked Russian officials, all presenting with a consistently reduced right arm swing in the absence of other overt neurological abnormalities. <b>Conclusions</b>&nbsp;We propose that this new gait pattern, which we term “gunslinger’s gait,” may result from a behavioural adaptation, possibly triggered by KGB or other forms of weapons training where trainees are taught to keep their right hand close to the chest while walking, allowing them to quickly draw a gun when faced with a foe. This should be included in the differential diagnosis of a unilaterally reduced arm swing.
Randomized phase II study of two different schedules of gemcitabine and oral TS-1 in chemo-naïve patients with advanced non-small cell lung cancer (NSCLC)
Authors: M. Satouchi, Y. Kotani, N. Katakami, T. Shimada, Y. Urata, S. Yoshimura, Y. Funada, A. Hata, M. Ando, S. Negoro
Journal: Journal of Clinical Oncology (2008)

8103 Background: TS-1, a novel oral fluorouracil derivative, has been shown to have anti-tumor activity with relatively mild adverse effects, and it is used in the treatment of NSCLC in Japan. The combination of gemcitabine (GEM) and 5-FU demonstrates a marked synergistic cytotoxic effect in a sequence-dependent manner in in vitro assay. This study was conducted in order to evaluate the efficacy and safety and to compare dosing schedules of gemcitabine combined with TS-1 in chemo-naïve NSCLC patients (pts). Methods: Pts with chemo-naive stage IIIB/IV NSCLC, an ECOG-PS of 0 or 1, and normal renal, liver, and bone marrow functions were randomized into 1 of 2 treatment arms. Oral TS-1 was administered daily from day 1 to 14, and GEM was given on days 1 and 8 (Arm A) or days 8 and 15 (Arm B). This cycle was repeated every 21 days. Results: A total of 80 pts were entered and 79 pts, treated in this trial. Randomization was well balanced across patient characteristics except for cell type (adenocarcinoma/squamous cell carcinoma = 37/4 (Arm A), 27/10 (Arm B)). Grade 3/4 hematological toxicities were neutropenia (54%), febrile neutropenia (9%), thrombocytopenia (11%) and anemia (4%). The hematological toxicity profiles did not differ very much between the two arms. Grade 3 pneumonitis was observed in 2 pts (3%). The response rate was 23.1% (95% confidence interval [CI]=11.1–39.3%) in Arm A and 30.6% (95% CI=16.3–46.1%), Arm B. Median time-to- progression (TTP) in Arm A was 4.1 months (95% CI=2.8–5.5) and Arm B, 5.4 months (95% CI=3.8–6.3) (p=0.75). Median survival time in Arm A was 15.7 months (95% CI=8.6–23.3) and Arm B, 22.4 months (95% CI=11.5-unknown) (p=0.32). Conclusions: The combination of GEM and TS-1 was determined to be feasible and effective for advanced NSCLC, and these results, particularly the favorable MST of Arm B, warrant further investigation of the Arm B dosing schedule for this combination for NSCLC. No significant financial relationships to disclose.
Abstract 13270: Relationship of Longitudinal Measurements of Biomarkers of Hemodynamic Stress, Systemic Inflammation, and Platelet Reactivity with Ischemic Outcomes in Non-ST-Elevation Acute Coronary Syndrome Patients Managed Without Revascularization
Authors: Mark Y Chan, Megan L Neely, Matthew T Roe, Shaun G Goodman, Jan H Cornel, Chunmei Zhou, Joseph A Jakubowski, Keith A Fox, Paul W Armstrong, Harvey D White, Dorairaj Prabhakaran, E. M Ohman, Kurt Huber
Journal: Circulation (2014)

Introduction: Hemodynamic stress, systemic inflammation, and platelet reactivity are key pathways mediating outcomes after acute coronary syndrome (ACS), but it remains uncertain how circulating biomarkers that reflect these pathways are associated and interconnected with ischemic outcomes in ACS patients who are managed without revascularization. Methods: We measured N-terminal pro B-type natriuretic peptide (NTproBNP; marker of hemodynamic stress), high-sensitivity C-reactive protein (hs-CRP; marker of systemic inflammation), and P2Y12 reaction units (PRU; marker of platelet reactivity measured by the VerifyNow device) at baseline and at 6 months in 1219 patients with non-ST-elevation ACS managed without revascularization and randomized to prasugrel vs clopidogrel in the TRILOGY-ACS trial. We tested the independent association of NTproBNP, hs-CRP, and PRU values with ischemic outcomes using Cox regression to adjust for baseline characteristics, including prior heart failure, Killip class, and biomarker ...
A message from the ERS President and the ERS Secretary for EU Affairs
Authors: Elisabeth Bel, Jean-Paul Sculier
Journal: European Respiratory Journal (2015)

We would like to emphasise to European Respiratory Society (ERS) members and to all physicians and researchers dealing with respiratory diseases the importance of the editorial written by Adoración Navarro-Torné and distinguished colleagues from the Health Directorate of DG Research and Innovation of the European Commission. The authors rightly note that chronic respiratory diseases (CRDs) (particularly chronic obstructive pulmonary disease (COPD) and asthma) and lung cancer are major causes of morbidity and mortality in the European Union, and have an important economic burden. The ERS leadership congratulates the European authorities on their support for respiratory research <http://ow.ly/RVMew>
Hospital trusts need “coherent plan” from government to reduce deficits, says spending watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The government must provide a clear plan for reducing the unsustainable level of deficit among NHS hospital trusts, the UK’s national spending watchdog has urged.

In a report published this week the National Audit Office (NAO) said that acute care hospital trusts in England had seen their finances worsen severely in the past 12 months and that the position was set to get even worse by the end of 2015-16.1

With demand for healthcare services continuing to rise, the NAO said that it was imperative that the Department of Health for England and its arm’s length bodies got to grips with the deficit and ensured that value for money was achieved.

The auditors highlighted that NHS trusts and foundation trusts posted a cumulative …
RETRACTED: SET1A Cooperates With CUDR to Promote Liver Cancer Growth and Hepatocyte-like Stem Cell Malignant Transformation Epigenetically
Authors: Tianming Li, Qidi Zheng, Jiahui An, Mengying Wu, Haiyan Li, Xin Gui, Hu Pu, Dongdong Lu
Journal: Molecular Therapy (2015)

Long noncoding RNA CUDR plays an important role during tumorigenesis. Herein, we demonstrate that SET1A cooperates with CUDR to accelerate hepatocarcinogenesis and promote malignant transformation of hepatocyte-like stem cells. Mechanistically, CUDR enhances the phosphorylation of RB1, C-myc expression, and the interplay between the SET1A and pRB1. Notably, CUDR acts as a sponge cushion that shows a link between SET1A and pRB1, producing a activated pRB1–SET1A complex. On the other hand, the pRB1–SET1A complex may carry methyls(me) to occupy the position of H3K4, resulting in specific tri-methylation of forth lysine of histone H3 (H3K4me3). Thereby, the H3K4me3 loads on the TRF2 promoter region which causes the TRF2 overexpression. Ultimately, the excessive TRF2 binds to telomere repeat DNA, prolonging the telomere length. These findings provide the first demonstration that SET1A cooperates with CUDR to play a positive potential role during hepatocarcinogenesis and hepatocyte-like stem cells' malignant transformation epigenetically. Long noncoding RNA CUDR plays an important role during tumorigenesis. Herein, we demonstrate that SET1A cooperates with CUDR to accelerate hepatocarcinogenesis and promote malignant transformation of hepatocyte-like stem cells. Mechanistically, CUDR enhances the phosphorylation of RB1, C-myc expression, and the interplay between the SET1A and pRB1. Notably, CUDR acts as a sponge cushion that shows a link between SET1A and pRB1, producing a activated pRB1–SET1A complex. On the other hand, the pRB1–SET1A complex may carry methyls(me) to occupy the position of H3K4, resulting in specific tri-methylation of forth lysine of histone H3 (H3K4me3). Thereby, the H3K4me3 loads on the TRF2 promoter region which causes the TRF2 overexpression. Ultimately, the excessive TRF2 binds to telomere repeat DNA, prolonging the telomere length. These findings provide the first demonstration that SET1A cooperates with CUDR to play a positive potential role during hepatocarcinogenesis and hepatocyte-like stem cells' malignant transformation epigenetically.
Neuropsychiatric, psychoeducational, and family characteristics of 14 juveniles condemned to death in the United States
Authors: D O Lewis, J H Pincus, B Bard, E Richardson, L S Prichep, M Feldman, C Yeager
Journal: American Journal of Psychiatry (1988)

Of the 37 juveniles currently condemned to death in the United States, all of the 14 incarcerated in four states received comprehensive psychiatric, neurological, neuropsychological, and educational evaluations. Nine had major neurological impairment, seven suffered psychotic disorders antedating incarceration, seven evidenced significant organic dysfunction on neuropsychological testing, and only two had full-scale IQ scores above 90. Twelve had been brutally physically abused, and five had been sodomized by relatives. For a variety of reasons the subjects' vulnerabilities were not recognized at the time of trial or sentencing, when they could have been used for purposes of mitigation.
Factor V Leiden (FVL) mutations and thromboembolic events (TE) in women with breast cancer on adjuvant tamoxifen
Authors: J. E. Garber, S. Halabi, E. Kaplan, S. Edge, L. Dressler, E. Paskett, N. Berliner
Journal: Journal of Clinical Oncology (2005)

508 Background: Tamoxifen (T) therapy has been associated with an increased risk of TE in women with breast cancer (BR) and in healthy women. In NSABP P-1, relative risk (RR) of DVT among women on T v. placebo was 1.60 (95% CI=0.91–2.86) and of PE was 3.01 (95% CI=1.15–9.27). FVL is a mutation in clotting Factor V that has been associated with increased TE risk with oral contraceptives and pregnancy. FVL was not associated with an increased risk of TE on T in high-risk women in NSABP P-1 or IBIS-1, but those analyses had small numbers of TE. Methods: A case-control study was conducted among CALGB institutions. Assuming a 1:2 case-control ratio, a total of 120 case-control sets were needed to provide 80% power to detect a RR=4 assuming a one-sided type I error rate= 0.05. Cases were 120 women who had had a documented DVT or PE while on adjuvant T, not necessarily on CALGB treatment trials. Controls were women with breast cancer who were taking or had taken adjuvant T with no TE, matched to the case on age at diagnosis (± 5 years). Data were collected on cancer stage, date of diagnosis, adjuvant chemotherapy use, smoking history and family TE history. Data on BMI and surgery (associated with TE on T in P-1 and IBIS, respectively) were not collected. Samples were analyzed for FVL mutations using multiplex PCR-based techniques. Conditional logistic regression was used to estimate the RR and 95% confidence interval. Results: This analysis is limited to 109 case-control triplets on whom complete data are available. Overall, 17 (15.6%) FVL mutations were seen in the cases; 10 (5%) in controls. The OR was 3.92 (95% CI=1.67 - 9.14, p<0.0001). Additional analysis will be provided. Conclusions: This is the largest case-control study designed to address the association between FVL and T-associated TE. The results from this study suggest that women with TE on T are almost 4 times more likely to have FVL than those without TE. Supported by Susan G. Komen Foundation. No significant financial relationships to disclose.
Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson's Disease and Other Brain Disorders
Authors: Hayate Javed, Sindhu A Menon, Karima M Al-Mansoori, Abdelmojib Al-Wandi, Nour K Majbour, Mustafa T Ardah, Shiji Varghese, Nishant N Vaikath, M Emdadul Haque, Mimoun Azzouz, Omar MA El-Agnaf
Journal: Molecular Therapy (2015)

Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability, for which there is no effective treatment available till date. Here, we report the development of nonviral vectors specific for neuronal cells that can deliver short interfering RNA (siRNA) against the α-synuclein gene (SNCA), and prevent PD-like symptoms both in vitro and in vivo. These vectors not only help siRNA duplexes cross the blood–brain barrier in mice, but also stabilize these siRNAs leading to a sustainable 60–90% knockdown of α-synuclein protein. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rapidly develop PD-like symptoms which were significantly alleviated when SNCA was knocked down using our vectors. Together, our data not only confirm the central role of α-synuclein in the onset of PD, but also provide a proof of principle that these nonviral vectors can be used as novel tools to design effective strategies to combat central nervous system diseases. Parkinson's disease (PD) is a debilitating neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability, for which there is no effective treatment available till date. Here, we report the development of nonviral vectors specific for neuronal cells that can deliver short interfering RNA (siRNA) against the α-synuclein gene (SNCA), and prevent PD-like symptoms both in vitro and in vivo. These vectors not only help siRNA duplexes cross the blood–brain barrier in mice, but also stabilize these siRNAs leading to a sustainable 60–90% knockdown of α-synuclein protein. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rapidly develop PD-like symptoms which were significantly alleviated when SNCA was knocked down using our vectors. Together, our data not only confirm the central role of α-synuclein in the onset of PD, but also provide a proof of principle that these nonviral vectors can be used as novel tools to design effective strategies to combat central nervous system diseases.
Enhancing the Prognostic Value of Cardiac Imaging With Multimodal Risk Assessment⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: W.H. Wilson Tang
Journal: JACC. Cardiovascular imaging (2009)

Progress in multimodality cardiac imaging has relied upon technological advances in providing better accuracy and quantification of the images of interest. Newer-generation cardiovascular diagnostic imaging tools are already equipped with unsurpassed capabilities to integrate a wide range of imaging