tbuckley/cabot-search huggingface dataset:
False positive endoscopic ultrasound fine needle aspiration cytology: incidence and risk factors
Authors: F. C. Gleeson, B. R. Kipp, J. L. Caudill, J. E. Clain, A. C. Clayton, K. C. Halling, M. R. Henry, E. Rajan, M. D. Topazian, K. K. Wang, M. J. Wiersema, J. Zhang, M. J. Levy
Journal: Gut (2010)

It is broadly accepted that the false positive (FP) rate for endoscopic ultrasound fine needle aspiration (EUS FNA) is 0-1%. It was hypothesised that the FP and false suspicious (FS) rates for EUS FNA are greater than reported. A study was undertaken to establish the rate and root cause of discordant interpretation.Using a prospectively maintained endoscopic database, cytohistological discordant EUS FNA examinations from 30 July 1996 to 31 December 2008 were identified retrospectively.Tertiary referral centre.Discordant FNA was defined by positive or suspicious FNA cytology in the absence of malignancy or neoplasm in the subsequent surgical pathology specimen, specifically in the absence of neoadjuvant therapy. Three cytopathologists conducted a blinded review of randomised discordant and matched specimens.FNA was performed in 5667/18 066 (31.4%) patients undergoing EUS, of whom 2547 had cytology results interpreted as 'positive' or 'suspicious' or 'atypical' for malignancy or neoplasm. Subsequent surgical resection without prior neoadjuvant therapy was performed in 377 patients with positive or suspicious cytology. The FP rate was 20/377 (5.3%) and increased to 27/377 (7.2%) when FS cases were included. The incidence of discordance was consistent over time (1996-2002: 10/118 (8.6%) vs 2003-2008: 17/259 (6.6%); p=0.5) and was higher in non-pancreatic FNA (15%) than pancreatic FNA (2.2%; p=0.0001). Two-thirds of the non-pancreatic FP cases involved sampling of perioesophageal or perirectal nodes in patients with luminal neoplasms or Barrett's oesophagus. Following pathological re-review, discordance was attributed to translocated cell contamination/sampling error (50%) or cytopathologist interpretive error (50%).These findings refute the accepted paradigm that FP cytology rarely occurs with EUS FNA. Further investigation revealed that FP FNA developed secondary to endosonographer technique or initial cytological misinterpretation, and is particularly likely when perioesophageal or perirectal nodes are aspirated in the setting of a luminal neoplasm or Barrett's oesophagus. Further study is needed to determine the significance of these findings and potential impact on the performance of FNA and patient outcomes.
Comparison of patients' exercise capacity according to the MRC classification and 6-minute walking test
Authors: Hamid Reza Khoddami Vishteh, Atekeh Hajilari, Masoomeh Masoudnia, Fariba Ghorbani, Shadi Shafaghi Shadi Shafaghi, Katayoun Najafizadeh
Journal: European Respiratory Journal (2012)

Background: Since the description of dyspnea varies from patients to patient and also varies in various cultures, the aim of this study was evaluation of Persian version of MRC dyspnea scale and comparison of it with results of an objective test, 6 minute walking test (6mw).  Methods: In this cross-sectional study, 150 consecutive patients with chief complaint of dyspnea who referred to the physiotherapy department of Dr Masih Daneshvari hospital, Tehran, Iran for performing 6mw were selected. The severity of dyspnea was assessed by MRC dyspnea scale.  Results: 51% were male and the mean age of patients was 47 yr. 87 (58%) had pulmonary diseases, 39 (26%) had cardiac diseases and 24 (16%) had dyspnea with unknown origin. The mean of disease duration was 8 yr and 23 (15%) used oxygen at home. Overall, 14% of patients were in level 1 MRC, 41% in level 2, 20% in level 3, 21% in level 4 and 4% in level 5. The mean (SD) of distance, decrease in oxygen saturation and increase in Borg dyspnea scale were 347 ± 117 m, 8 ± 8% and 2 ± 2, respectively. Levels of MRC dyspnea scale were negatively correlated with distance (r=-0.500, P  Conclusion: Findings of our study showed that there are good correlation between MRC dyspnea scale and 6mw test. Since the assessment of level of function of patients with dyspnea is necessary for evaluating progression of the disease and 6mw test needs skilled personnel and appropriate place, MRC dyspnea scale could be a good alternate.  Keyword: Dyspnea, MRC dyspnea scale, 6 minute walking test, Pulmonary disease, Cardiac disease.
Pathogenesis of necrotising enteritis with special reference to intestinal hypersensitivity reactions.
Authors: S N Arseculeratne, R G Panabokke, C Navaratnam
Journal: Gut (1980)

The aetiological aspects of 83 sporadic cases of necrotising enteritis (NE) have been studied. Of 56 cases in which histology of the intestine was possible, eight showed appearances (oedema and local eosinophilia) suggestive of a type I hypersensitivity reaction, while in 37 the appearances were suggestive of a type III reaction. We suggest that these reactions, which were more common in children and young adults, were initiating factors in the intestinal necrosis. The type III reactions (submucosal arteritis, fibrinoid necrosis of arteriolar walls, intramural and perivascular infiltration with polymorphonuclear, mononuclear, and eosinophil cells, and submucous oedema) were in seven cases accompanied by extraintestinal lesions (hypercellularity of glomeruli, amorphous material in the Bowman9s capsular space, tubular casts, mononuclear cell infiltration into the hepatic portal tracts, congestion and oedema of the lung) which were compatible with systemic immune complex disease. The mesenteric lymph nodes in 12 out of 15 cases with intestinal arteritis showed appearances indicative of a humoral immune response. We suggest that NE is a two-stage process. In stage 1, a necrotic focus is established in the intestinal mucosa-submucosa by 9initiating9 factors of vascular (functional or organic) or microbial (exotoxic, endotoxic, or Shwartzman) origin. Functional circulatory insufficiency in the intestine is of particular relevance to necrotising enteritis in neonates and in adults with traumatic shock or cardiac insufficiency. The jejunal and--to a lesser extent--the ileal microcirculation appear to be particularly vulnerable to microcirculatory insufficiency. Ninety-seven per cent of our cases were of NE of the small intestine of which 76% involved the jejunum alone or as a part of a jejunoileitis. These 9initiating9 factors act either singly or synergistically with 9promoting9 factors (changes in the volume, composition, or pH of the diet, intestinal stasis, or bacterial factors) in the establishment of necrotic foci in the intestine. Stage 2 results from the colonisation of the necrotic foci by intestinal clostridia, the toxigenic capacity of which will determine the progress of the intestinal lesion. Clinically established NE is essentially gas gangrene of the intestinal wall. Our bacteriological findings (microscopic, cultural, and serological) support a pathogenetic role of Cl. welchii in the established stages of necrotising enteritis. Strains of Cl. welchii from NE cases had significantly higher histidine decarboxylase activity than strains from control sources; it is possible that the resultant histamine production could act as a promoting factor in stage 1. Neutralising antibody against the Wanowrie virus, an Asian arbovirus which produces haemorrhagic enteritis in mice, was absent in the paired sera from 10 cases examined.
Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials
Authors: Mark T Dransfield, Jean Bourbeau, Paul W Jones, Nicola A Hanania, Donald A Mahler, Jørgen Vestbo, Andrew Wachtel, Fernando J Martinez, Frank Barnhart, Lisa Sanford, Sally Lettis, Courtney Crim, Peter MA Calverley
Journal: The Lancet Respiratory Medicine (2013)
Facial Emotion Labeling Deficits in Children and Adolescents at Risk for Bipolar Disorder
Authors: Melissa A Brotman, Amanda E Guyer, Evin S Lawson, Sarah E Horsey, Brendan A Rich, Daniel P Dickstein, Daniel S Pine, Ellen Leibenluft
Journal: American Journal of Psychiatry (2008)

Objective: Research has revealed facial emotion labeling deficits in children and adolescents with bipolar disorder. To assess whether such impairments may be an endophenotype for bipolar disorder, the authors examined facial emotion identification proficiency in children who were at risk for bipolar disorder because they had a first-degree relative with the illness. Method: The facial expressions subtests of the Diagnostic Analysis of Nonverbal Accuracy scale were administered to 52 patients with bipolar disorder, 24 at-risk youths, and 78 control subjects, all 4–18 years of age. Results: Compared with the control group, both the bipolar and at-risk groups made more errors identifying facial emotions. The number of errors did not differ significantly between the bipolar and at-risk groups. Conclusions: Deficits in facial emotion labeling may be a risk marker for bipolar disorder. Further study is needed to determine the neural mechanisms involved, as well as to explore other emotional processing impairments in youths at risk for bipolar disorder and to identify genetic associations.
Population-based assessment of the outcomes in patients with postcolonoscopy colorectal cancers
Authors: Anand Govindarajan, Linda Rabeneck, Lingsong Yun, Jill Tinmouth, Lawrence F Paszat, Nancy N Baxter
Journal: Gut (2015)

<h3>Objective</h3> The potential for cancers to not be detected on colonoscopy is increasingly recognised, but little is known about patient outcomes. The objective of this study was to assess the outcomes of patients diagnosed with postcolonoscopy colorectal cancers (PCCRCs). <h3>Design</h3> We conducted a population-based retrospective cohort study, including all patients diagnosed with colorectal cancer (CRC) in Ontario, Canada from 2003 to 2009. Patients were categorised into three groups: DETECTED (diagnosed within 6 months of first colonoscopy), PCCRC (diagnosed 6–36 months after first colonoscopy) or NOSCOPE (no colonoscopy within 36 months of diagnosis). Univariate and multivariable analyses were conducted to study overall survival, surgical treatment, emergency presentation and surgical complications. <h3>Results</h3> Overall, 45 104 patients were included, with 2804 being classified as having a PCCRC. Compared with the DETECTED group, PCCRC was associated with a significantly higher likelihood of stage IV disease (17.2% vs 12.9%), worse overall survival (5 year OS: 60.8% vs 68.3%, p&lt;0.0001; adjusted HR: 1.25, 95% CI 1.17 to 1.32, p&lt;0.0001), a higher likelihood of emergency presentation (OR: 2.86, 95% CI 2.56 to 3.13, p&lt;0.001) and lower likelihood of surgical resection (OR: 0.61, 95% CI 0.55 to 0.67, p&lt;0.001). However, patients with PCCRC had significantly better outcomes than those in the NOSCOPE group (stage IV: 37.1%, 5 year OS: 38.9%) <h3>Conclusions</h3> Compared with CRC detected by colonoscopy, PCCRCs are associated with a higher risk of emergent presentation, a lower likelihood of surgical resection and most notably, significantly worse oncological outcomes. However, they have better outcomes than patients with no recent colonoscopy.
Comparison of initial versus delayed introduction of a treat-to-target strategy in patients with recent-onset rheumatoid arthritis: results of the T-4 3-year study
Authors: Yukitomo Urata, Yoshihide Nakamura, Ken-ichi Furukawa
Journal: Annals of the Rheumatic Diseases (2013)

We investigated whether a delayed treat-to-target strategy introduction was disadvantageous compared with the clinical, radiological, and functional efficacy of initial introduction on early rheumatoid arthritis (RA) after a 3-year follow-up (T-4 3-year) study.

Between August 2008 and April 2010, 243 early RA patients (symptom duration <3 years) were randomly allocated to one of four strategy groups; we focus here on the routine care (R group) and the disease activity score in 28 joints (DAS28)1 plus matrix metalloproteinase (MMP)-3-driven therapy (T group)2 (figure 1).3 The T-4 3-year study followed a 1-year study. At 56 weeks, all subjects were allocated to the T group (R→T, RT group; T→T, TT group, etc.), and visits were every 4 weeks; the clinical variable assessment, each physician's articular examination and DAS28 calculations were every 12 weeks and at baseline.



Figure 1 
Subject disposition and study flow chart (A), tapering methods of biological agents (BA) (B) and percentage of subjects who met triple criteria for comprehensive disease remission over time (C–F) (non-responder imputation). (A) Investigators may have listed more than one reason. (B) …
Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex
Authors: Deshui Jia, Rui Dong, Ying Jing, Dan Xu, Qifeng Wang, Lei Chen, Qigen Li, Yuping Huang, Yuannv Zhang, Zhenfeng Zhang, Li Liu, Shan Zheng, Qiang Xia, Hongyang Wang, Kuiran Dong, Xianghuo He
Journal: Hepatology (2014)

Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the β-catenin gene that lead to constitutive activation of the Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of six paired HB tumors and their corresponding lymphocytes. This identified 24 somatic nonsynonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP, and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the β-catenin in 42 HB tumors. We further used short hairpin RNA (shRNA)-mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that one novel oncogene (CAPRIN2) and three tumor suppressors (SPOP, OR5I1, and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. These results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis.
Accelerometer-based measures in physical activity surveillance: current practices and issues
Authors: Željko Pedišić, Adrian Bauman
Journal: British Journal of Sports Medicine (2014)

Self-reports of physical activity (PA) have been the mainstay of measurement in most non-communicable disease (NCD) surveillance systems. To these, other measures are added to summate to a comprehensive PA surveillance system. Recently, some national NCD surveillance systems have started using accelerometers as a measure of PA. The purpose of this paper was specifically to appraise the suitability and role of accelerometers for population-level PA surveillance.A thorough literature search was conducted to examine aspects of the generalisability, reliability, validity, comprehensiveness and between-study comparability of accelerometer estimates, and to gauge the simplicity, cost-effectiveness, adaptability and sustainability of their use in NCD surveillance.Accelerometer data collected in PA surveillance systems may not provide estimates that are generalisable to the target population. Accelerometer-based estimates have adequate reliability for PA surveillance, but there are still several issues associated with their validity. Accelerometer-based prevalence estimates are largely dependent on the investigators' choice of intensity cut-off points. Maintaining standardised accelerometer data collections in long-term PA surveillance systems is difficult, which may cause discontinuity in time-trend data. The use of accelerometers does not necessarily produce useful between-study and international comparisons due to lack of standardisation of data collection and processing methods. To conclude, it appears that accelerometers still have limitations regarding generalisability, validity, comprehensiveness, simplicity, affordability, adaptability, between-study comparability and sustainability. Therefore, given the current evidence, it seems that the widespread adoption of accelerometers specifically for large-scale PA surveillance systems may be premature.
Duration of Untreated Psychosis and Time to Treatment Response for Delusions and Hallucinations
Authors: Handan Gunduz-Bruce, Marjorie McMeniman, Delbert G. Robinson, Margaret G. Woerner, John M. Kane, Nina R. Schooler, Jeffrey A. Lieberman
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Duration of untreated psychosis is associated with time to treatment response among patients with schizophrenia. However, individual psychotic symptoms have not been investigated in this context. The authors examined the relationship between duration of untreated psychosis and time to response for hallucinations and delusions. METHOD: Data were available for 118 patients with first-episode schizophrenia in a longitudinal treatment study. Patients received open-label treatment with conventional antipsychotics and were followed for up to 5 years. Duration of untreated psychosis was correlated with time to response for delusions and hallucinations, and predictors of time to response were examined. RESULTS: Time to response for delusions was significantly longer than that for hallucinations. Duration of untreated psychosis was significantly correlated with time to response for delusions but not for hallucinations. In regression analyses, duration of untreated psychosis was the only predictor for time to response for delusions; it was not a predictor for hallucinations. CONCLUSIONS: The results suggest that duration of untreated psychosis may be specifically associated with time to response for delusions. This association may have clinical implications.
Effect of Prone Positioning on Clinical Outcomes in Children With Acute Lung Injury
Authors: Martha A. Q. Curley, Patricia L. Hibberd, Lori D. Fineman, David Wypij, Mei-Chiung Shih, John E. Thompson, Mary Jo C. Grant, Frederick E. Barr, Natalie Z. Cvijanovich, Lauren Sorce, Peter M. Luckett, Michael A. Matthay, John H. Arnold
Journal: JAMA (2005)

In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known.To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning.Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded.Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines.Ventilator-free days to day 28.The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, -0.2 days; 95% CI, -3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, -3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure-free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28.Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.
Characterization of an in vivo concentration-effect relationship for piperaquine in malaria chemoprevention
Authors: Martin Bergstrand, François Nosten, Khin Maung Lwin, Mats O. Karlsson, Nicholas J. White, Joel Tarning
Journal: Science Translational Medicine (2014)

An in vivo concentration-effect relationship for the malaria drug piperaquine can be used for translational simulations of expected therapeutic outcomes in vulnerable populations.
CLONAL EVOLUTION OF GLIOMAS IS ENCODED IN THE EVOLUTIONARY DYNAMICS OF DNA METHYLATION
Authors: J. F. Costello, T. Mazor, A. Pankov, B. E. Johnson, C. Hong, R. J. A. Bell, I. V. Smirnov, G. F. Reis, J. J. Phillips, M. Barnes, A. W. Bollen, B. S. Taylor, A. M. Molinaro, A. B. Olshen, J. S. Song, M. S. Berger, S. M. Chang, J. F. Costello
Journal: Neuro-Oncology (2014)

BACKGROUND: The clonal evolution of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast, tumor epigenetic states are reversible and sensitive to the tumor microenvironment, presumably precluding the use of epigenetics to discover the clonal and sub-clonal evolution of tumors. We recently used mutation patterns to learn how low grade gliomas evolve over time, and also discovered that temozolomide treatment of LGG is associated with TMZ-induced hypermutation and malignant progression to GBM (BE Johnson et al, Science, 2014). METHODS: We used exome and RNA sequencing, DNA methylation arrays, along with computational analysis to construct phylogenetic and phyloepigenetic relationships among co-evolving tumor cell populations. RESULTS: Here we examined the spatial and temporal dynamics of DNA methylation in our clinically and genetically characterized cohort of IDH1-mutant low-grade gliomas and their patient-matched recurrences. While all tumors exhibited the hypermethylation signature associated with IDH1 mutation, low-grade gliomas that underwent spontaneous or temozolomide-associated malignant progression to high-grade glioblastoma multiforme (GBM) had a unique signature of DNA hypomethylation enriched for both active enhancers, and sites of age-related hypermethylation in the brain. Genes with promoter hypomethylation and concordant transcriptional upregulation during evolution to GBM were enriched in cell cycle function, evolving in concert with genetic alterations that deregulate the G1/S cell cycle checkpoint. Despite the plasticity of tumor epigenetic states, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations in the same patients. CONCLUSIONS: These findings highlight widespread co-dependency of genetic and epigenetic events throughout the clonal evolution of initial and recurrent gliomas.