tbuckley/cabot-search huggingface dataset:
Proposed Diagnostic Criteria for the Brugada Syndrome
Authors: Arthur A.M. Wilde, Charles Antzelevitch, Martin Borggrefe, Josep Brugada, Ramón Brugada, Pedro Brugada, Domenico Corrado, Richard N.W. Hauer, Robert S. Kass, Koonlawee Nademanee, Silvia G. Priori, Jeffrey A. Towbin
Journal: Circulation (2002)
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration
Authors: A. Liberati, D. G Altman, J. Tetzlaff, C. Mulrow, P. C Gotzsche, J. P A Ioannidis, M. Clarke, P J Devereaux, J. Kleijnen, D. Moher
Journal: BMJ (2009)

Systematic reviews and meta-analyses are essential to summarise evidence relating to efficacy and safety of healthcare interventions accurately and reliably. The clarity and transparency of these reports, however, are not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (quality of reporting of meta-analysis) statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realising these issues, an international group that included experienced authors and methodologists developed PRISMA (preferred reporting items for systematic reviews and meta-analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this explanation and elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA statement, this document, and the associated website (www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
S129 Predicting outcome from HIV-associated pneumocystis pneumonia
Authors: D. Armstrong-James, A. J. Copas, P. D. Walzer, S. G. Edwards, R. F. Miller
Journal: Thorax (2010)

<h3>Background</h3> The presentation of <i>Pneumocystis jirovecii</i> pneumonia (PCP) ranges from mild to severe. The former responds to antimicrobial therapy, the latter has a high mortality rate despite treatment. Several studies have described clinical and laboratory factors that are predictive of death from PCP. Our objectives were to create a prognostic scoring model to aid the clinician in predicting outcome from HIV-associated PCP. <h3>Methods</h3> A prognostic scoring model was built using risk factors identifiable at/soon after hospitalisation, that is, ‘by the bedside’— which have previously been identified as being associated with mortality from PCP (a repeat episode of PCP, the patient9s age, their haemoglobin (Hb), PaO<sub>2</sub> (breathing room air), both on admission, the presence of co-morbidity (Comorb), such as lymphoma or pregnancy, and the presence of pulmonary Kaposi sarcoma (PKS) (Walzer PD, <i>et al</i> CID 2008;46:625–33). The model was built from data concerning 592 consecutive episodes of PCP that had occurred among 540 patients presenting to a specialist inpatient HIV treatment centre. <h3>Results</h3> The prognostic scoring model was: [25.5 + (age in years/10) + 2 (if a repeat episode of PCP) + 4 (if PKS detected) + 4 (if Comorb present)−PaO<sub>2</sub> – Hb]. The prognostic model produced scores ranging from 0 to 20; median (IQR)=9 (7–11). Testing interactions between risk factors and time showed the model to be applicable across all time periods. Patients were divided into five groups according to prognostic score: 0–3.9=group 1, 4–7.9=group 2, 8–11.9=group 3, 12–15.9=group 4, 16 or greater =group 5. Abstract S129 Table 1 shows mortality rates among the 540 patients with PCP, grouped according to their prognostic scores. <h3>Conclusions</h3> While this prognostic scoring model requires further validation in patient cohorts from other healthcare institutions, it is potentially a simple ‘by the bedside’ method of identifying patients early in their hospital admission who are at high and low risk of in-hospital death from PCP and so may aid the clinician in assessing the severity of illness and in deciding on treatment strategies.
Immunosuppressive effects of 1,2 5-dihydroxyvitamin D3 and its analogue calcipotriol on epidermal cells
Authors: M. BAGOT, D. CHARLIE, M.-C. LESCS, R. PAMPHILE, J. REVUZ
Journal: British Journal of Dermatology (1994)

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)2D3, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T-cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)2D3 and calcipotriol on the human allogeneic mixed epidermal cell-lymphocyte reaction. All experiments were performed both with 1,25(OH)2D3, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)2D3 resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC-depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle-treated LC. These calcitriol-pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected, LC-depleted keratinocytes failed to stimulate allogenic lymphocytes. When added to autologous unmodified EC, however, calcitriol-pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle-treated keratinocytes. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2-h or 24-h pulse with 1,25(OH)2D3 or calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitochondrial Genome of the Colorless Green Alga Polytomella parva: Two Linear DNA Molecules with Homologous Inverted Repeat Termini
Authors: Jinshui Fan, Robert W. Lee
Journal: Molecular Biology and Evolution (2002)

Most of the well-characterized mitochondrial genomes from diverse green algal lineages are circular mapping DNA molecules; however, Chlamydomonas reinhardtii has a linear 15.8 kb unit mitochondrial genome with 580 or 581 bp inverted repeat ends. In mitochondrial-enriched fractions prepared from Polytomella parva (=P. agilis), a colorless, naturally wall-less relative of C. reinhardtii, we have detected two linear mitochondrial DNA (mtDNA) components with sizes of 13.5 and 3.5 kb. Sequences spanning 97% and 86% of the 13.5- and 3.5-kb mtDNAs, respectively, reveal that these molecules contain long, at least 1.3 kb, homologous inverted repeat sequences at their termini. The 3.5-kb mtDNA has only one coding region (nad6), the functionality of which is supported by both the relative rate at which it has accumulated nonsynonymous nucleotide substitutions and its absence from the 13.5-kb mtDNA which encodes nine genes (i.e., large and small subunit rRNA [LSU and SSU rRNA] genes, one tRNA gene, and six protein-coding genes). On the basis of DNA sequence data, we propose that a variant start codon, GTG, is utilized by the P. parva 13.5-kb mtDNA-encoded gene, nad5. Using the relative rate test with Chlamydomonas moewusii (=C. eugametos) as the outgroup, we conclude that the nonsynonymous nucleotide substitution rate in the mitochondrial protein-coding genes of P. parva is on an average about 3.3 times that of the C. reinhardtii counterparts.
Application of Molecular Profiling in Clinical Trials for Advanced Metastatic Cancers
Authors: S. Kummar, P. M. Williams, C.-J. Lih, E. C. Polley, A. P. Chen, L. V. Rubinstein, Y. Zhao, R. M. Simon, B. A. Conley, J. H. Doroshow
Journal: JNCI Journal of the National Cancer Institute (2015)

There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach.
Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals
Authors: M. Bækvad-Hansen, B.G. Nordestgaard, M. Dahl
Journal: European Respiratory Journal (2010)

The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T&gt;C), rs2077079 (-18A&gt;C) and rs3024791 (-384G&gt;A)) associate with reduced lung function and risk of COPD in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status. None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV 1 ) % predicted, forced vital capacity (FVC) % pred and FEV 1 /FVC overall or among smokers (p = 0.25–0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p = 0.17–0.78). Similar results were obtained for hospitalisation due to COPD (p = 0.07–0.93); we could exclude overall hazard ratios for heterozygotes of 1.18–1.21 and for homozygotes of 1.25–1.57 or larger for all three polymorphisms. In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine.
Quality in primary care
Authors: B. Guthrie, T. Dreischulte
Journal: BMJ (2014)

Individual doctors matter, and pay for performance may reduce hospital admissions

The United Kingdom has led the world in several national policy initiatives to improve the quality of primary care, notably by implementing both nationwide surveys of patient experience and the largest healthcare pay for performance scheme in the world—the Quality and Outcomes Framework. This makes the United Kingdom fertile ground for examining the many uncertainties surrounding these policy initiatives, two of which are examined in the linked papers (doi:10.1136/bmj.g6034, doi:10.1136/bmj.g6423).1 2

Roberts and colleagues used multilevel modelling to explore whether variation in patient experience was due more to individual doctors or to the practices within which they worked.1 The doctors were responsible for 3.5 times more variation than the practices in patients’ experience of communication in the consultation, and 6.5 times more variation in whether or not patients trusted their doctor. In contrast, much more variation existed between practices than between the doctors for four indicators measuring aspects of patient experience that are less under the control of individual practitioners, such as cleanliness of buildings or ease of access.1 This is consistent with the few other studies that have rigorously examined variation in outcome at both individual and institutional level,3 suggesting, for example, that blood pressure measurement for patients with diabetes varies more between …
Modulation of the Lung Colonization of B16-F1 Melanoma Cells by Citrus Pectin
Authors: David Platt, Avraham Raz
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Modulation of the Lung Colonization of B16-F1 Melanoma Cells by Citrus Pectin Get access David Platt, David Platt Search for other works by this author on: Oxford Academic PubMed Google Scholar Avraham Raz Avraham Raz Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Pages 438–442, https://doi.org/10.1093/jnci/84.6.438 Published: 18 March 1992 Article history Received: 21 August 1991 Revision received: 06 December 1991 Accepted: 17 December 1991 Published: 18 March 1992
A Pharmacologic Inhibitor of the Protease Taspase1 Effectively Inhibits Breast and Brain Tumor Growth
Authors: David Y. Chen, Yishan Lee, Brian A. Van Tine, Adam C. Searleman, Todd D. Westergard, Han Liu, Ho-Chou Tu, Shugaku Takeda, Yiyu Dong, David R. Piwnica-Worms, Kyoung J. Oh, Stanley J. Korsmeyer, Ann Hermone, Richard Gussio, Robert H. Shoemaker, Emily H.-Y. Cheng, James J.-D. Hsieh
Journal: Cancer Research (2011)

The threonine endopeptidase Taspase1 has a critical role in cancer cell proliferation and apoptosis. In this study, we developed and evaluated small molecule inhibitors of Taspase1 as a new candidate class of therapeutic modalities. Genetic deletion of Taspase1 in the mouse produced no overt deficiencies, suggesting the possibility of a wide therapeutic index for use of Taspase1 inhibitors in cancers. We defined the peptidyl motifs recognized by Taspase1 and conducted a cell-based dual-fluorescent proteolytic screen of the National Cancer Institute diversity library to identify Taspase1 inhibitors (TASPIN). On the basis of secondary and tertiary screens the 4-[(4-arsonophenyl)methyl]phenyl] arsonic acid NSC48300 was determined to be the most specific active compound. Structure-activity relationship studies indicated a crucial role for the arsenic acid moiety in mediating Taspase1 inhibition. Additional fluorescence resonance energy transfer-based kinetic analysis characterized NSC48300 as a reversible, noncompetitive inhibitor of Taspase1 (K(i) = 4.22 μmol/L). In the MMTV-neu mouse model of breast cancer and the U251 xenograft model of brain cancer, NSC48300 produced effective tumor growth inhibition. Our results offer an initial preclinical proof-of-concept to develop TASPINs for cancer therapy.
Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis
Authors: A Jacoby
Journal: Gut (2005)

<b>Background and aims:</b> Study of health related quality of life (HRQOL) and the factors responsible for its impairment in primary biliary cirrhosis (PBC) has, to date, been limited. There is increasing need for a HRQOL questionnaire which is specific to PBC. The aim of this study was to develop, validate, and evaluate a patient based PBC specific HRQOL measure. <b>Subjects and methods:</b> A pool of potential questions was derived from thematic analysis of indepth interviews carried out with 30 PBC patients selected to represent demographically the PBC patient population as a whole. This pool was systematically reduced, pretested, and cross validated with other HRQOL measures in national surveys involving a total of 900 PBC patients, to produce a quality of life profile measure, the PBC-40, consisting of 40 questions distributed across six domains. The PBC-40 was then evaluated in a blinded comparison with other HRQOL measures in a further cohort of 40 PBC patients. <b>Results:</b> The six domains of PBC-40 relate to fatigue, emotional, social, and cognitive function, general symptoms, and itch. The highest mean domain score was seen for fatigue and the lowest for itch. The measure has been fully validated for use in PBC and shown to be scientifically sound. PBC patient satisfaction, measured in terms of the extent to which a questionnaire addresses the problems that they experience, was significantly higher for the PBC-40 than for other HRQOL measures. <b>Conclusion:</b> The PBC-40 is a short easy to complete measure which is acceptable to PBC patients and has significantly greater relevance to their problems than other frequently used HRQOL measures. Its scientific soundness, shown in extensive testing, makes it a valuable instrument for future use in clinical and research settings.
Molecular Characterization of Gastric Neuroendocrine Carcinoma Based on Extensive Sequence Variation and Genome-Wide Methylation Analysis
Authors: T. Ando, A. Hosokawa, S. Nanjo, A. Ueda, H. Mihara, S. Kajiura, H. Fujinami, H. Yohita, J. Nishikawa, T. Sugiyama
Journal: Annals of Oncology (2014)
Developmental Remodeling of the Internal Elastic Lamina of Rabbit Arteries
Authors: Lisa C. Y. Wong, B. Lowell Langille
Journal: Circulation Research (1996)

Abstract We examined remodeling of the internal elastic lamina (IEL) of rabbit arteries from 3 to 23 weeks of age. The IELs were fenestrated at all ages; however, the sizes of the fenestrae increased dramatically during postnatal development. Mean areas occupied by the individual fenestrae of the carotid artery IEL increased from 11.3±0.7 μm 2 in 3-week-old rabbits to 61.2±5.5 μm 2 in adult rabbits. The estimated number of fenestrae per vessel also increased greatly, from 2.68×10 5 to 9.27×10 5 ; however, the increased number of fenestrae did not keep pace with growth of the artery, since fenestrae per square millimeter decreased by 26%. Large increases in the size of fenestrae were also observed in the renal and iliac arteries, although greater decreases in fenestrae per square millimeter occurred with age (70% in iliac arteries). Morphological assessments suggested that enlarging fenestrae frequently fuse with neighbors. By contrast with other arteries, the IEL of the abdominal aorta was not a continuous fenestrated sheet in young animals, perhaps reflecting the extensive remodeling that this vessel undergoes in the postnatal period. We decreased common carotid blood flow by 70% in 5 rabbits at 10 weeks of age by ligating the ipsilateral external carotid artery, and we approximately doubled blood flow in 5 others at the same age, by contralateral common carotid ligation. At 15 weeks of age, fenestrae in the artery carrying increased flow were 39% larger than fenestrae in the control artery, whereas fenestrae were 53.5% smaller after 70% decreases in flow ( P &lt;.05). We conclude that flow-dependent enlargement of fenestrae contributes to developmental remodeling of the IEL. Remodeling of the IEL may also have important implications for transport of materials and cell-cell communication between the intima and media.
Eradication of Microscopic Lymph Node Metastases After Injection of Living BeG Adiacent to the Primary Tumor
Authors: Howard G. Smith, Robert C. Bast, Berton Zbar, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1975)

Guinea pigs with established intradermal tumors and microscopic axillary lymph node metastases were treated with a combination of surgery and BCG. The tumors were excised and BCG was given in attempts to eliminate residual malignant disease. Injection of BCG into established intradermal tumors 7 days before local excision successfully eradicated microscopic axillary lymph node metastases and cured significant numbers of animals. Injection of BCG into dermal tumors 20 minutes or 1 day before excision prolonged survival but did not cure a significant number of animals. Injection of BCG into the skin adjacent to the dermal tumor 7 days before local excision eradicated microscopic axillary lymph node metastases. However, such injection 1 day before local excision did not eradicate metastases. BCG administered by intravenous, intra-arterial, or intranodal injection did not eliminate reidual malignant disease. Several factors were evaluated as possible correlates of successful immunotherapy. The development of tuberculin hypersensitivity, the magnitude of regional adenopathy, and the number of BCG organisms in axillary nodes were not useful correlates. Histologically, the presence of tumor cells, multiple focal granuloma, or histiocytosis in axillary nodes faiiled to correlate with results of therapy. The development of tumor-specific transplantation immunity provided the best correlate of successful immunotherapy.
Screening Adult Survivors of Childhood Cancer for Cardiomyopathy: Comparison of Echocardiography and Cardiac Magnetic Resonance Imaging
Authors: Gregory T. Armstrong, Juan Carlos Plana, Nan Zhang, Deokumar Srivastava, Daniel M. Green, Kirsten K. Ness, F. Daniel Donovan, Monika L. Metzger, Alejandro Arevalo, Jean-Bernard Durand, Vijaya Joshi, Melissa M. Hudson, Leslie L. Robison, Scott D. Flamm
Journal: Journal of Clinical Oncology (2012)

To compare two-dimensional (2D) echocardiography, the current method of screening for treatment-related cardiomyopathy recommended by the Children's Oncology Group Guidelines, to cardiac magnetic resonance (CMR) imaging, the reference standard for left ventricular (LV) function.Cross-sectional, contemporaneous evaluation of LV structure and function by 2D and three-dimensional (3D) echocardiography and CMR imaging in 114 adult survivors of childhood cancer currently median age 39 years (range, 22 to 53 years) exposed to anthracycline chemotherapy and/or chest-directed radiation therapy.In this survivor population, 14% (n = 16) had an ejection fraction (EF) less than 50% by CMR. Survivors previously undiagnosed with cardiotoxicity (n = 108) had a high prevalence of EF (32%) and cardiac mass (48%) that were more than two standard deviations below the mean of normative CMR data. 2D echocardiography overestimated the mean EF of this population by 5%. Compared with CMR, 2D echocardiography (biplane method) had a sensitivity of 25% and a false-negative rate of 75% for detection of EF less than 50%, although 3D echocardiography had 53% and 47%, respectively. Twelve survivors (11%) had an EF less than 50% by CMR but were misclassified as ≥ 50% (range, 50% to 68%) by 2D echocardiography (biplane method). Detection of cardiomyopathy was improved (sensitivity, 75%) by using a higher 2D echocardiography cutoff (EF < 60%) to detect an EF less than 50% by the reference standard CMR.CMR identified a high prevalence of cardiomyopathy among adult survivors previously undiagnosed with cardiac disease. 2D echocardiography demonstrated limited screening performance. In this high-risk population, survivors with an EF 50% to 59% by 2D echocardiography should be considered for comprehensive cardiac assessment, which may include CMR.