tbuckley/cabot-search huggingface dataset:
Case-control studies of risk factors for primary biliary cirrhosis in two United Kingdom populations
Authors: M I Prince, S J Ducker, O F W James
Journal: Gut (2010)

The aetiology of primary biliary cirrhosis (PBC) is largely unknown. Previous studies have indicated that both environmental and genetic risk factors may be important.We undertook a large case-control study to study possible risk factors in more detail. All patients were sent postal questionnaires on risk factors.We identified two sets of PBC cases from a geographically defined epidemiology study (epidemiological cases) and from a survey of the national patient support group (Foundation cases). Controls were selected from the electoral roll in strata matched to epidemiological cases by quartiles of age and sex.Analysable questionnaires were received from 318 epidemiological cases, 2258 Foundation cases and 2438 controls. Statistically significant associations were seen with smoking (OR=1.63 (95% CI, 1.27 to 2.09)), epidemiological cases versus controls (1.57 (1.39 to 1.78)), Foundation cases versus controls, hair dye use (1.37 (0.98 to 1.80)), 1.25 (1.07 to 1.46)), and with previous histories of psoriasis (1.90 (1.21 to 1.91), 2.33 (1.03 to 1.73)), urinary infections (2.06 (1.56 to 0.1.73), 1.80 (1.54 to 2.11)), and shingles (2.38 (1.82 to 3.11), 1.23 (1.08 to 1.43)) and previous autoimmune diseases. Alcohol consumption was negatively associated with PBC (0.57 (0.39 to 0.83), 0.73 (0.61 to 0.79)). We did not identify any associations with obstetric risk factors except a previous history of obstetric cholestasis (2.13 (1.25 to 3.59), 2.20 (1.61 to 3.03)).We have confirmed that among environmental risk factors, smoking and the use of some cosmetics as well as urinary infections appear important. Among possible genetic risk factors a family history of PBC is a strong association and that a previous history of obstetric cholestasis as another putative 'genetic' risk.
BTS guideline for emergency oxygen use in adult patients
Authors: B R O'Driscoll, L S Howard, A G Davison
Journal: Thorax (2008)

### Philosophy of the guideline ### Assessing patients Figure 1 Chart 1: Oxygen prescription for acutely hypoxaemic patients in hospital. ABG, arterial blood gas; COPD, chronic obstructive pulmonary disease; Fio2, fraction of inspired oxygen; ICU, intensive care unit; NIV, non-invasive ventilation; Pco2, carbon dioxide tension; Spo2, arterial oxygen saturation measured by pulse oximetry. View this table: Table 1 Critical illnesses requiring high levels of supplemental oxygen (see section 8.10) ### Oxygen prescription View this table: Table 2 Serious illnesses requiring moderate levels of supplemental oxygen if the patient is hypoxaemic (section 8.11) View this table: Table 3 COPD and other conditions requiring controlled or low-dose oxygen therapy (section 8.12) ### Oxygen administration Figure 2 Chart 2: Flow chart for oxygen administration on general wards in hospitals. ABG, arterial blood gas; EPR, electronic patient record; EWS, Early Warning Score; Spo2, arterial oxygen saturation measured by pulse oximetry. ### Monitoring and maintenance of target saturation
Continuous and intermittent exercise responses in individuals with chronic obstructive pulmonary disease
Authors: S Sabapathy
Journal: Thorax (2004)

<b>Background:</b> While the acute physiological responses to continuous exercise have been well documented in individuals with chronic obstructive pulmonary disease (COPD), no previous study has examined the response to intermittent exercise in these patients. <b>Methods:</b> We examined the physiological responses of 10 individuals with moderate COPD (forced expiratory volume in 1 second 52 (15)% predicted) who performed both an intermittent (1 min exercise and rest intervals) and a continuous cycle ergometer test on separate days. Both intermittent and continuous exercise tests were performed at the same power output, calculated as 70% of the peak power attained during an incremental exercise test. <b>Results:</b> Intermittent exercise was associated with significantly lower values for oxygen uptake, carbon dioxide output, expired ventilation, heart rate, plasma lactate concentration, and ratings of breathlessness than continuous exercise. Subjects were able to complete a significantly greater total amount of work during intermittent exercise (71 (32) kJ) than during continuous exercise (31 (24) kJ). The degree of dynamic lung hyperinflation (change in end expiratory lung volume) was significantly lower during intermittent exercise (0.23 (0.07) l) than in continuous exercise (0.52 (0.13) l). <b>Conclusions:</b> The greater amount of work performed and lower measured physiological responses achieved with intermittent exercise may allow for greater peripheral training adaptations in individuals with more limited lung function. The results suggest that intermittent exercise may be superior to continuous exercise as a mode of training for patients with COPD.
Does the Clinical Examination Predict Lower Extremity Peripheral Arterial Disease?
Authors: Nadia A Khan, Sherali A Rahim, Sonia S Anand, David L Simel, Akbar Panju
Journal: JAMA (2006)

Lower extremity peripheral arterial disease (PAD) is common and associated with significant increases in morbidity and mortality. Physicians typically depend on the clinical examination to identify patients who need further diagnostic testing.To systematically review the accuracy and precision of the clinical examination for PAD.MEDLINE (January 1966 to March 2005) and Cochrane databases were searched for articles on the diagnosis of PAD based on physical examination published in the English language. Included studies compared an element of the history or physical examination with a reference standard of ankle-brachial index, duplex sonography, or angiogram. Seventeen of the 51 potential articles identified met inclusion criteria. Two of the authors independently extracted data, performed quality review, and used consensus to resolve any discrepancies.For asymptomatic patients, the most useful clinical findings to diagnose PAD are the presence of claudication (likelihood ratio [LR], 3.30; 95% confidence interval [CI], 2.30-4.80), femoral bruit (LR, 4.80; 95% CI, 2.40-9.50), or any pulse abnormality (LR, 3.10; 95% CI, 1.40-6.60). While none of the clinical examination features help to lower the likelihood of any degree of PAD, the absence of claudication or the presence of normal pulses decreases the likelihood of moderate to severe disease. When considering patients who are symptomatic with leg complaints, the most useful clinical findings are the presence of cool skin (LR, 5.90; 95% CI, 4.10-8.60), the presence of at least 1 bruit (LR, 5.60; 95% CI, 4.70-6.70), or any palpable pulse abnormality (LR, 4.70; 95% CI, 2.20-9.90). The absence of any bruits (iliac, femoral, or popliteal) (LR, 0.39; 95% CI, 0.34-0.45) or pulse abnormality (LR, 0.38; 95% CI, 0.23-0.64) reduces the likelihood of PAD. Combinations of physical examination findings do not increase the likelihood of PAD beyond that of individual clinical findings. However, when combinations of clinical findings are all normal, the likelihood of disease is lower than when individual symptoms or signs are normal. A PAD scoring system, which includes auscultation of arterial components by handheld Doppler, provides greater diagnostic accuracy.Clinical examination findings must be used in the context of the pretest probability because they are not independently sufficient to include or exclude a diagnosis of PAD with certainty. The PAD screening score using the hand-held Doppler has the greatest diagnostic accuracy.
Lack of Erythroid Characteristics in la-Positive Leukemia Cell Lines Induced by Friend Murine Leukemia Virus: Brief Communication 2
Authors: Bruce Chesebro, Kathy Wehrly, David Housman
Journal: JNCI Journal of the National Cancer Institute (1978)

A group of mouse leukemia cell lines induced by the Friend murine leukemia virus (F-MuLV) was examined for la cell membrane antigens (regulated by the l-region of the H-2 complex), as well as for erythroid characteristics. Erythroid traits tested were hemoglobin synthesis, incorporation of59Fe into heme, and presence of globin mRNA. Of 19 lines, 13 were positive for erythroid characteristics. All of these 13 lines were la-negative. Of 19 lines, 6 were negative for erythroid characteristics, and 5 of the 6 were la-positive. The data suggested that F-MuLV-induced leukemogenesis may operate in more than 1 cell type. In addition to the primitive erythroid type of cell usually involved in leukemia induced by F-MuLV, nonerythroid la-positive cells may also be transformed. The exact origin of the la-positive leukemia cells is unknown.
Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells
Authors: Jin‐xing Wei, Li‐hong Lv, Yun‐le Wan, Yang Cao, Guo‐lin Li, Hao‐ming Lin, Rui Zhou, Chang‐zhen Shang, Jun Cao, Hai He, Qing‐fang Han, Pei‐qing Liu, Gang Zhou, Jun Min
Journal: Hepatology (2014)

The deregulation of microRNAs (miRNAs) plays an important role in human hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in hepatocellular carcinoma (HCC) cells. First, we examined the different miRNA expression profiles in HCC cells and HCC cell–derived exosomes. Next, coculture experiments indicated that HCC cell–derived exosomes promoted the cell growth, migration, and invasion of HCC cells and had the ability to shuttle miRNAs to recipient cells. Further, our data showed that Vps4A, a key regulator of exosome biogenesis, was frequently down‐regulated in HCC tissues. The reduction of Vps4A in HCC tissues was associated with tumor progression and metastasis. In vitro studies revealed that Vps4A repressed the growth, colony formation, migration, and invasion of HCC cells. We further investigated the role and involvement of Vps4A in suppressing the bioactivity of exosomes and characterized its ability to weaken the cell response to exosomes. By small RNA sequencing, we demonstrated that Vps4A facilitated the secretion of oncogenic miRNAs in exosomes as well as accumulation and uptake of tumor suppressor miRNAs in cells. A subset of Vps4A‐associated miRNAs was identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the phosphatidylinositol‐3‐kinase/Akt signaling pathway was the most likely candidate pathway for modulation by these miRNAs. Indeed, we proved that the phosphatidylinositol‐3‐kinase/Akt pathway was inactivated by Vps4A overexpression. Conclusion : Exosome‐mediated miRNA transfer is an important mechanism of self‐modulation of the miRNA expression profiles in HCC cells, and Vps4A may function as a tumor suppressor, which utilizes exosomes as mediators to regulate the secretion and uptake of miRNAs in hepatoma cells; these observations provide new insights into the development of HCC. (H epatology 2015;61:1284–1294)
Infections in the survivors of out-of-hospital cardiac arrest in the first 7 days
Authors: Min-Shan Tsai, Wen-Chu Chiang, Chien-Chang Lee, Cheng-Chun Hsieh, Patrick Chow-In Ko, Chiung-Yuan Hsu, Chan-Ping Su, Shey-Ying Chen, Wei-Tein Chang, Ang Yuan, Matthew Huei-Ming Ma, Shyr-Chyr Chen, Wen-Jone Chen
Journal: Intensive Care Medicine (2005)
T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity.
Authors: J A Gracie, E M Bolton, C Porteous, J A Bradley
Journal: The Journal of Experimental Medicine (1990)

This study has examined the cellular and humoral responses underlying the rejection of rat renal allografts bearing an isolated RT1Aa class I MHC disparity. RT1Aa disparate kidneys were rejected promptly by high responder RT1u but not by low responder RT1c recipients (median survival time 10 d and greater than 100 d, respectively). The magnitude and phenotype of the cellular infiltrate were similar in rejecting and nonrejecting RT1Aa disparate kidneys. Paradoxically, graft infiltrating cells and spleen cells from RT1u recipients showed minimal ability to lyse donor strain lymphoblasts in vitro, whereas effector cells from RT1c recipients showed modest levels of cytotoxicity. Injection of RT1u rats with MRC OX8 mAb was highly effective at selectively depleting CD8+ cells from graft recipients but had no effect in prolonging the survival of RT1Aa disparate grafts despite the complete absence of CD8+ cells from the graft infiltrate, which included numerous CD4+ T cells and macrophages. RT1u, but not RT1c, recipients mounted a strong alloantibody response against RT1Aa disparate kidneys. Immune serum obtained from RT1u recipients that had rejected a RT1Aa disparate graft was able, when injected into cyclosporin-treated RT1u recipients, to restore their ability to reject a RT1Aa, but not a third-party RT1c, kidney. These results suggest that CD8+ cells in general and CD8+ cytotoxic effector cells in particular are unnecessary for the rapid rejection of RT1Aa class I disparate kidney grafts by high responder RT1u recipients. By implication, CD4+ T cells alone are sufficient to cause prompt rejection of such grafts and they may do so by providing T cell help for the generation of alloantibody.
Representations, computation, and inverse ecological optics
Authors: Heiko Neumann
Journal: Behavioral and Brain Sciences (1998)

Implicit and explicit filling-in phenomena should be distinguished. Blind spot phenomena and mechanisms of boundary completion can be accounted for by implicit filling-in. Surface regions are “painted” with perceptual quantities, such as brightness, by explicit filling-in. “Filling-in” and “finding-out” relate to different computational tasks. Mechanisms of purposive computation (e.g., for navigation) evaluate local measurements, thus “finding out”; whereas mechanisms for grasping might require passive reconstruction, thus “filling in.”
Evidence for Polygenic Adaptation to Pathogens in the Human Genome
Authors: Josephine T. Daub, Tamara Hofer, Emilie Cutivet, Isabelle Dupanloup, Lluis Quintana-Murci, Marc Robinson-Rechavi, Laurent Excoffier
Journal: Molecular Biology and Evolution (2013)

Most approaches aiming at finding genes involved in adaptive events have focused on the detection of outlier loci, which resulted in the discovery of individually "significant" genes with strong effects. However, a collection of small effect mutations could have a large effect on a given biological pathway that includes many genes, and such a polygenic mode of adaptation has not been systematically investigated in humans. We propose here to evidence polygenic selection by detecting signals of adaptation at the pathway or gene set level instead of analyzing single independent genes. Using a gene-set enrichment test to identify genome-wide signals of adaptation among human populations, we find that most pathways globally enriched for signals of positive selection are either directly or indirectly involved in immune response. We also find evidence for long-distance genotypic linkage disequilibrium, suggesting functional epistatic interactions between members of the same pathway. Our results show that past interactions with pathogens have elicited widespread and coordinated genomic responses, and suggest that adaptation to pathogens can be considered as a primary example of polygenic selection.
Soluble CD95 concentrations are increased in patients with severe systemic lupus erythematosus, but not in their first degree relatives
Authors: M W van der Linden
Journal: Annals of the Rheumatic Diseases (2001)

Plasma concentrations of soluble CD95 (sCD95) are raised in patients with systemic lupus erythematosus (SLE) before clinical relapses become manifest. Increased sCD95 concentrations may therefore be a familial characteristic that is associated with susceptibility to severe disease. To test this, sCD95 concentrations were measured in healthy first degree relatives of patients with severe and non-severe SLE.Seventy seven first degree relatives of 26 patients with severe, and 72 relatives of 25 patients with non-severe lupus were studied. Controls were 42 first degree relatives of 17 patients with chronic cutaneous lupus erythematosus (CCLE) and 63 partners of the patients with their first degree relatives. Severe lupus was defined as both multi-organ disease and cyclophosphamide treatment, non-severe lupus as neither. Organ damage was assessed with the SLICC-ACR index, disease activity with SLEDAI.Soluble CD95 concentrations in relatives of patients with severe SLE were similar to those in relatives of patients with non-severe SLE, relatives of patients with CCLE, and controls (median (interquartile range) sCD95 concentration 0.59 (0.52-0.66) v 0.57 (0.50-0.63), 0.56 (0.51-0.71), and 0.55 (0.49-0.61) ng/ml, p=0.25, p=0.94, and p=0.17, respectively). Increased concentrations of sCD95, however, were found in patients with severe SLE compared with those in patients with non-severe SLE, patients with CCLE, and control relatives (0.77 (0.70-0.97) v 0.60 (0.54-0.67), 0.57 (0.54-0.71), and 0.57 (0.52-0.63) ng/ml, respectively, p<0.001). Concentrations of sCD95 were significantly correlated with damage index scores (rs=0.47, p<0.01). Basic and clinical characteristics of patients with SLE, including SLEDAI scores, could not explain these observations.Soluble CD95 concentrations are associated with severity of the disease and not with susceptibility for severe SLE.
Reliable and Sensitive Identification of Occult Tumor Cells Using the Improved Rare Event Imaging System
Authors: Stine-Kathrein Kraeft, Andras Ladanyi, Kevin Galiger, Anna Herlitz, Andrew C. Sher, Danielle E. Bergsrud, Gaelle Even, Stephanie Brunelle, Lyndsay Harris, Ravi Salgia, Tom Dahl, John Kesterson, Lan Bo Chen
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to assess the feasibility of using rare event imaging system (REIS)-assisted analysis to detect occult tumor cells (OTCs) in peripheral blood (PB). The study also sought to determine whether REIS-assisted OTC detection presents a clinically viable alternative to manual microscopic detection to establish the true significance of OTC from solid epithelial tumors. Experimental Design: We recently demonstrated proof of concept using a fluorescence-based automated microscope system, REIS, for OTC detection from the PB. For this study, the prototype of the system was adopted for high-throughput and high-content cellular analysis. Results: The performance of the improved REIS was examined using normal blood (n = 10), normal blood added to cancer cells (n = 20), and blood samples obtained from cancer patients (n = 80). Data from the screening of 80 clinical slides from breast and lung cancer patients, by manual microscopy and by the REIS, revealed that as many as 14 of 35 positive slides (40%) were missed by manual screening but positively identified by REIS. In addition, REIS-assisted scanning reliably and reproducibly quantified the total number of cells analyzed in the assay and categorized positive cells based on their marker expression profile. Conclusions: REIS-assisted analysis provides excellent sensitivity and reproducibility for OTC detection. This approach may enable an improved method for screening of PB samples and for obtaining novel information about disease staging and about risk evaluation in cancer patients.
Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory.
Authors: M Quiding, I Nordström, A Kilander, G Andersson, L A Hanson, J Holmgren, C Czerkinsky
Journal: Journal of Clinical Investigation (1991)

We have examined secretory antibody and cell-mediated immune responses to oral cholera vaccine in the human gastrointestinal mucosa. Freshly isolated peripheral blood lymphocytes and intestinal lymphocytes obtained by enzymatic dispersion of duodenal biopsies were assayed for numbers of total and vaccine specific immunoglobulin-secreting cells by enzyme-linked immunospot assay (ELISPOT) techniques; the frequency of cells secreting interferon-gamma (IFN-gamma) was also examined by a new modification of the ELISPOT technique. After booster immunizations with oral cholera vaccine, large numbers of cholera toxin-specific antibody-secreting cells (ASC) appeared in the small intestine. The responses were dominated by IgA ASC. A single immunization, performed 5 mo after the initial vaccinations, gave rise to an ASC response similar to that seen after the first booster immunization, with respect to both magnitude and isotype distribution. Each of the immunizations also evoked an ASC response in blood which was of lower magnitude than that seen in the small intestine, and comprised similar proportions of IgA and IgG ASC. A booster immunization also resulted in increased frequencies of IFN-gamma-secreting cells, but this increase was confined to the duodenal mucosa. This study establishes the feasibility of studying, at the single-cell level, intestinal immune reactivity in humans. Furthermore, it indicates that the small intestinal mucosa is an enriched source of IFN-gamma. It also demonstrates marked differences between intestinal and peripheral blood immune responses after enteric immunization, and confirms the notion that the mucosal immune system in humans displays immunological memory.
5(S),15(S)-dihydroxyeicosatetraenoic acid and lipoxin generation in human polymorphonuclear cells: dual specificity of 5-lipoxygenase towards endogenous and exogenous precursors.
Authors: C Chavis, I Vachier, P Chanez, J Bousquet, P Godard
Journal: The Journal of Experimental Medicine (1996)

5-Lipoxygenase activation of human blood polymorphonuclear cells (PMN) from asthmatic patients (asthmatics) was studied to investigate whether differences may exist with healthy subjects (controls). The respective cell capacities to produce lipoxins (LXs), leukotrienes, and 5(S), 15(S)-dihydroxyeicosatetraenoic acid [5(S),15(S)-diHETE] were compared under in vitro stimulation by ionophore A23187, with or without exogenous 15(S)-hydroxyeicosatetraenoic acid [15(S)-diHETE]. Eicosanoids were analyzed by elution with an isocratic reverse-phase high performance liquid chromatography system, and their profiles, detected by simultaneous monitoring at 302, 280, and 246 nm, were evaluated on the basis of chromatographic behavior: UV spectral characteristics and coelution with synthetic standards. In the presence of exogenous 15(S)-HETE, human PMN were able to produce LXs and 5(S),15(S)-diHETE, PMN from asthmatics were able to produce 5(S), 5(S),15(S)-diHETE, and LXs from endogenous sources, whereas in the same experimental conditions, no detectable amounts of these compounds were released by PMN from controls. The levels of 5(S),15(S)-diHETE, and LXs biosynthesized from endogenous arachidonic acid were highly correlated. Two different LX patterns were observed involving two possible metabolic pathways: (a) via the intermediate 5,6-epoxytetraene alone for LXs generation from exogenous 15(S)-HETE; and (b) via 5,6- and/or 14,15-epoxytetraenes leading to the formation of an enzyme-bound delocalized carbocation for LXs generation from endogenous arachidonate, respectively. The enhanced 5-lipoxygenase activation of blood PMN from asthmatics and the metabolism of exogenous 15(S)-HETE may reflect a priming induced by various mediators released from environmental cells, and could be considered as a model of transcellular signalization between PMN and endothelial cells.