tbuckley/cabot-search huggingface dataset:
The Requirement for Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor in Leukocyte-Mediated Immune Glomerular Injury
Authors: A. Richard Kitching, Xiao Ru Huang, Amanda L. Turner, Peter G. Tipping, Ashley R. Dunn, Stephen R. Holdsworth
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Proliferative glomerulonephritis in humans is characterized by the presence of leukocytes in glomeruli. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can potentially stimulate or affect T cell, macrophage, and neutrophil function. To define the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis, glomerular injury was studied in mice genetically deficient in either GM-CSF (GM-CSF −/− mice) or G-CSF (G-CSF −/− mice). Two models of glomerulonephritis were studied: neutrophil-mediated heterologous-phase anti-glomerular basement membrane (GBM) glomerulonephritis and T cell/macrophage-mediated crescentic autologous-phase anti-GBM glomerulonephritis. Both GM-CSF −/− and G-CSF −/− mice were protected from heterologous-phase anti-GBM glomerulonephritis compared with genetically normal (CSF WT) mice, with reduced proteinuria and glomerular neutrophil numbers. However, only GM-CSF −/− mice were protected from crescentic glomerular injury in the autologous phase, whereas G-CSF −/− mice were not protected and in fact had increased numbers of T cells in glomeruli. Humoral responses to the nephritogenic antigen were unaltered by deficiency of either GM-CSF or G-CSF, but glomerular T cell and macrophage numbers, as well as dermal delayed-type hypersensitivity to the nephritogenic antigen, were reduced in GM-CSF −/− mice. These studies demonstrate that endogenous GM-CSF plays a role in experimental glomerulonephritis in both the autologous and heterologous phases of injury.
The adventitia may be a barrier specific to nitric oxide in rabbit pulmonary artery.
Authors: R H Steinhorn, F C Morin, J A Russell
Journal: Journal of Clinical Investigation (1994)

To determine whether the adventitia that surrounds pulmonary vessels acts as a barrier specific to nitric oxide, special lucite chambers were constructed to measure the force of contraction of rabbit pulmonary artery rings in which the endothelial or adventitial surfaces could be preferentially exposed to nitric oxide (NO), carbon monoxide (CO), or sodium nitroprusside (SNP). Delivery of NO to the endothelial and adventitial surfaces of preconstricted vessels produced markedly different concentration-response curves with maximal relaxations of 89 +/- 3 and 11 +/- 9%, respectively. In contrast, relaxations induced by both CO and SNP did not differ significantly between endothelial and adventitial exposure to these agents. Placement of a layer of pericardium onto the endothelial surface eliminated relaxation to the endothelial delivery of NO but not to CO. We conclude that the pulmonary vascular response to NO displays a striking sidedness which is not observed either with CO, another gas of similar molecular weight, or with SNP, both of which cause relaxation by stimulating guanylate cyclase. The elimination of NO but not CO relaxations with a layer of pericardium may indicate that the adventitia acts as a barrier specific to NO. This directionality of effect provides evidence for a highly localized regulation of pulmonary vascular tone by endothelial cell NO and also indicates that extravascular NO may have limited access to pulmonary vascular smooth muscle.
Peroxisome Proliferator-Activated Receptor γ–Independent Suppression of Androgen Receptor Expression by Troglitazone Mechanism and Pharmacologic Exploitation
Authors: Chih-Cheng Yang, Yu-Chieh Wang, Shuo Wei, Li-Fang Lin, Chang-Shi Chen, Cheng-Chun Lee, Cheng-Chieh Lin, Ching-Shih Chen
Journal: Cancer Research (2007)

Previously, we showed that the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone at high doses was able to suppress androgen receptor (AR) expression in LNCaP prostate cancer cells independently of PPARgamma. Pharmacologic exploitation of this finding led to STG28, a PPARgamma-inactive analogue of troglitazone with substantially higher potency in AR repression. Considering the pivotal role of AR in prostate tumorigenesis, this study investigates the mechanism by which troglitazone and derivatives suppress AR expression in LNCaP cells. Reverse transcription-PCR and reporter gene assays indicate that this drug-induced AR repression occurs at both mRNA and protein levels. Evidence suggests that troglitazone and derivatives mediate the transcriptional repression of AR by facilitating the ubiquitin-dependent proteasomal degradation of the transcriptional factor Sp1. These agents also cause the proteolysis of two proteins that regulate Sp1-mediated transcription (i.e., the TATA-binding protein-associated factor TAF(II)250 and cyclin D1). However, their involvement in the transcriptional repression of AR is refuted by the finding that small interfering RNA knockdown of these two regulatory proteins does not cause AR down-regulation. STG28 does not cause significant reduction in Sp1 or AR expression in normal prostate epithelial cells. This discriminatory effect underscores the differential susceptibility of malignant versus normal cells to the inhibitory effect of STG28 on cell viability. From a translational perspective, STG28 provides a proof of principle that potent AR-ablative agents could be developed through structural modifications of troglitazone. Moreover, as the control of Sp1 degradation remains unclear, STG28 represents a unique pharmacologic probe to investigate the ubiquitin-proteasome system that regulates Sp1 proteolysis.
Combining community-based research and local knowledge to confront asthma and subsistence-fishing hazards in Greenpoint/Williamsburg, Brooklyn, New York.
Authors: Jason Corburn
Journal: Environmental Health Perspectives (2002)

Activists in the environmental justice movement are challenging expert-driven scientific research by taking the research process into their own hands and speaking for themselves by defining, analyzing, and prescribing solutions for the environmental health hazards confronting communities of the poor and people of color. I highlight the work of El Puente and The Watchperson Project--two community-based organizations in the Greenpoint/Williamsburg neighborhood in Brooklyn, New York, that have engaged in community-based participatory research (CBPR) to address asthma and risks from subsistence-fish diets. The CBPR process aims to engage community members as equal partners alongside scientists in problem definition, information collection, and data analysis--all geared toward locally relevant action for social change. In the first case I highlight how El Puente has organized residents to conduct a series of asthma health surveys and tapped into local knowledge of the Latino population to understand potential asthma triggers and to devise culturally relevant health interventions. In a second case I follow The Watchperson Project and their work surveying subsistence anglers and note how the community-gathered information contributed key data inputs for the U.S. Environmental Protection Agency Cumulative Exposure Project in the neighborhood. In each case I review the processes each organization used to conduct CBPR, some of their findings, and the local knowledge they gathered, all of which were crucial for understanding and addressing local environmental health issues. I conclude with some observations about the benefits and limits of CBPR for helping scientists and communities pursue environmental justice.
Presentation of the Same Glycolipid by Different CD1 Molecules
Authors: A. Shamshiev, H.-J. Gober, A. Donda, Z. Mazorra, L. Mori, G. De Libero
Journal: The Journal of Experimental Medicine (2002)

Five CD1 molecules are expressed in humans and it is unclear whether they have specialized or redundant functions. We found that sulfatide is a promiscuous CD1-binding ligand and have isolated T cell clones that are specific for sulfatide and restricted by distinct CD1 molecules. These clones have been used to compare the capacity of different CD1 to present the same glycolipid, to induce effector functions, and to form persistent immunogenic complexes. CD1a, CD1b, and CD1c molecules similarly load sulfatide on the cell surface without processing, and prime Th1 and Th2 responses. Stimulation by sulfatide-loaded CD1a persists much longer than that by CD1b and CD1c in living cells. Use of recombinant soluble CD1a confirmed the prolonged capacity to stimulate T cells. Moreover, other glycosphingolipids bind to all CD1, which suggests the presence of additional promiscuous ligands. Thus, group I CD1 molecules present an overlapping set of self-glycolipids, even though they are quite divergent from an evolutionary point of view.
Clinical characteristics and prognostic factors of pulmonary MALT lymphoma
Authors: R. Borie, M. Wislez, G. Thabut, M. Antoine, A. Rabbat, L-J. Couderc, I. Monnet, H. Nunes, F-X. Blanc, H. Mal, A. Bergeron, D. Dusser, D. Israël-Biet, B. Crestani, J. Cadranel
Journal: European Respiratory Journal (2009)

Mucosa-associated lymphoid tissue-derived (MALT) lymphoma, a low grade B-cell extranodal lymphoma, is the most frequent subset of primary pulmonary lymphoma. Our objective was to evaluate the initial extent of disease and to analyse the characteristics and long-term outcome of these patients. All chest and pathological departments of teaching hospitals in Paris were contacted in order to identify patients with a histological diagnosis of primary pulmonary lymphoma of the MALT subtype. 63 cases were identified. The median age was 60 yrs. 36% of cases had no symptoms at diagnosis. 46% of patients had at least one extrapulmonary location of lymphoma. The estimated 5- and 10-yr overall survival rates were 90% and 72%, respectively. Only two of the nine observed deaths were related to lymphoma. Age and performance status were the only two adverse prognostic factors for survival. Extrapulmonary location of lymphoma was not a prognostic factor for overall survival or for progression-free survival. Treatment with cyclophosphamide or anthracycline was associated with shorter progression-free survival, when compared with chlorambucil. The survival data confirm the indolent nature of pulmonary MALT lymphoma. Better progression-free survival was observed with chlorambucil when compared with cyclophosphamide or anthracycline.
Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial
Authors: Sarah A Frech, Herbert L DuPont, A Louis Bourgeois, Robin McKenzie, Jaime Belkind-Gerson, Jose F Figueroa, Pablo C Okhuysen, Norma H Guerrero, Francisco G Martinez-Sandoval, Juan HM Meléndez-Romero, Zhi-Dong Jiang, Edwin J Asturias, Jane Halpern, Olga R Torres, Ana S Hoffman, Christina P Villar, Raniya N Kassem, David C Flyer, Bo H Andersen, Kazem Kazempour, Sally A Breisch, Gregory M Glenn
Journal: The Lancet (2008)
Recognising the importance of national respiratory audits
Authors: C. E. Bucknall, N. A. Maskell
Journal: Thorax (2011)

Assessment of the quality of care has come to prominence over the past two decades with the increasing realisation that healthcare delivery is an increasingly complex task, that mistakes happen and that the process can be treated as a system to which the same techniques as are used in industry can be applied.

Quality assurance and quality improvement are the twin aims of the recently revamped British Thoracic Society (BTS) audit system, which has the added benefit of providing nationwide snap shots of current practice which can feed into guideline review and patient advocacy programmes.

The web-based system currently runs eight …
In vitro investigations of jet-pulses for the measurement of respiratory impedance in newborns
Authors: M Schmidt, B Foitzik, O Hochmuth, G Schmalisch
Journal: European Respiratory Journal (1999)

The aim of this in vitro study was to investigate the measuring range and accuracy of a miniaturized equipment for respiratory impedance (Zrs) measurements in newborns using jet-pulses. Brief flow pulses (peak flow=16 L x min(-1), width=10 ms) were generated by a jet-generator consisting of a solenoid valve and an injector, situated between pneumotachograph and outflow resistance. Serially arranged resistance-inertance-compliance (R-I-C) lung models (RM=1.3-6.4 kPa x L(-1) x s, CM=7.4-36.9 mL x kPa(-1), IM=1.5 Pa x L(-1) x s2) were used to measure the real and imaginary part of Zrs between 4 and 50 Hz and to determine R, C and I by means of the method of least squares. The median errors for R, C and I were -0.1 kPa x L(-1) x s (-2%), 2.4 mL x kPa(-1)(13%) and -0.2 Pa x L(-1) x s2 (-13%) for measurements without breathing signals and 0.11 kPa x L(-1) -s (3%), 3 mL x kPa(-1) (16%) and 0.28 Pa x L (-1) x s2 (19%) in mechanically ventilated models. During spontaneous breathing the influence of the breathing flow on Zrs was negligible. The equipment did not show any nonlinearity when different pulse amplitudes were used (Vmax=13-22 L x min(-1)). The investigations have shown that jet-pulses allow reliable measurements of respiratory impedance and have the potential to provide valuable information about lung mechanics in spontaneously breathing and mechanically ventilated newborns. The developed measuring head has a low apparatus dead space, is easy to disinfect, has standard connections and can be used as the T-piece in a ventilator circuit.
Characterization of genetic variation in <i><scp>TLR</scp>8</i> in relation to allergic rhinitis
Authors: V. Henmyr, C. Lind‐Halldén, D. Carlberg, C. Halldén, E. Melén, M. Wickman, A. Bergström, T. Säll, L. O. Cardell
Journal: Allergy (2015)

A previous investigation of all 10 TLR genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. This study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.The TLR8 gene was resequenced in 288 AR patients from Malmö and the data were compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared.Sequencing detected 13 polymorphisms (three promotor and 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF < 1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR association tests made using the BAMSE cohort yielded five P-values <0.05. Tests of IgE levels yielded four significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects, and response to different allergens in the different populations.Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveals contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR.
Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors
Authors: Panagiotis D. Kottaridis, Rosemary E. Gale, Stephen E. Langabeer, Marion E. Frew, David T. Bowen, David C. Linch
Journal: Blood (2002)
Why schools should promote students’ health and wellbeing
Authors: Chris Bonell, Neil Humphrey, Adam Fletcher, Laurence Moore, Rob Anderson, Rona Campbell
Journal: BMJ (2014)

<h3>Objectives</h3> Increased exposure to digital devices as part of online classes increases susceptibility to visual impairments, particularly among school students taught using e-learning strategies. This study aimed to identify the impact of remote learning during the COVID-19 lockdown on children’s visual health. <h3>Design</h3> Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. <h3>Data sources</h3> Scopus, PubMed and ScienceDirect databases from the year 2020 onwards. <h3>Eligibility criteria</h3> We included cross-sectional, case–control, cohort studies, case series and case reports, published in English, Spanish or French, that approached the effects of remote learning during the COVID-19 lockdown on visual health in neurotypical children. <h3>Data extraction and synthesis</h3> We included a total of 21 articles with previous quality assessments using the Joanna Briggs checklist. Risk of bias assessment was applied using the National Institutes of Health quality assessment tool for before-and-after studies with no control group; the tool developed by Hoy <i>et al</i> to assess cross-sectional studies; the Murad <i>et al</i> tool to evaluate the methodological quality of case reports and case series; and the Newcastle-Ottawa Scale for cohort studies. <h3>Results</h3> All but one study reported a deleterious impact of the COVID-19 lockdown on visual health in children. Overall, the most frequently identified ocular effects were refractive errors, accommodation disturbances and visual symptoms such as dry eye and asthenopia. <h3>Conclusions</h3> Increased dependence on digital devices for online classes has either induced or exacerbated visual disturbances, such as rapid progression of myopia, dry eye and visual fatigue symptoms, and vergence and accommodation disturbances, in children who engaged in remote learning during the COVID-19 lockdown. <h3>PROSPERO registration number</h3> CRD42022307107.
Orthopaedic surgery in 255 patients with inflammatory arthropathies: longitudinal effects on pain, physical function and health-related quality of life
Authors: H Osnes-Ringen, T K Kvien, J E Henriksen, P Mowinckel, H Dagfinrud
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To examine the effectiveness of orthopaedic surgery in patients with inflammatory arthropathies with regard to longitudinal changes in pain, physical function and health-related quality of life and explore differences in effectiveness between replacement versus non-replacement surgery and surgery in the upper versus the lower limb. <h3>Methods:</h3> 255 patients (mean age 57.5 years (SD 13.1), 76.7% female) with inflammatory arthropathies underwent orthopaedic surgical treatment and responded to mail surveys at baseline and during follow-up (3, 6, 9 and 12 months). The booklet of questionnaires included the arthritis impact measurement scales 2 (AIMS2), health assessment questionnaire (HAQ), short form 36 (SF-36), EQ-5D and visual analogue scales (VAS) addressing patient global, fatigue, general pain and pain in the actual joint. Standardised response means (SRM) were calculated to estimate the magnitude of improvement. <h3>Results:</h3> Significant improvement was seen for most of the dimensions of health, the largest improvement for pain in the actual joint (SRM 1.17) at one year follow-up. SRM for AIMS-2 physical, SF-36 physical and HAQ were 0.1, 0.48 and 0.05, respectively. The overall numeric improvement (SRM) in utility was 0.10 (0.37) with EQ-5D and 0.03 (0.27) with SF-6D. Improvement overall was similar after surgery in the upper versus the lower limb, but was larger in patients undergoing replacement surgery than in patients undergoing other surgical procedures (SRM 1.54 vs 1.08 for pain in the actual joint). <h3>Conclusions:</h3> Surgical procedures have a major positive impact on pain in the actual joint, but improvement is less in other dimensions of health. Health benefits were larger after replacement surgery than after other surgical procedures.
Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by Integrating TCGA Data
Authors: Yitan Zhu, Yanxun Xu, Donald L. Helseth, Kamalakar Gulukota, Shengjie Yang, Lorenzo L. Pesce, Riten Mitra, Peter Müller, Subhajit Sengupta, Wentian Guo, Jonathan C. Silverstein, Ian Foster, Nigel Parsad, Kevin P. White, Yuan Ji
Journal: JNCI Journal of the National Cancer Institute (2015)

Genetic interactions play a critical role in cancer development. Existing knowledge about cancer genetic interactions is incomplete, especially lacking evidences derived from large-scale cancer genomics data. The Cancer Genome Atlas (TCGA) produces multimodal measurements across genomics and features of thousands of tumors, which provide an unprecedented opportunity to investigate the interplays of genes in cancer. We introduce Zodiac, a computational tool and resource to integrate existing knowledge about cancer genetic interactions with new information contained in TCGA data. It is an evolution of existing knowledge by treating it as a prior graph, integrating it with a likelihood model derived by Bayesian graphical model based on TCGA data, and producing a posterior graph as updated and data-enhanced knowledge. In short, Zodiac realizes “Prior interaction map + TCGA data → Posterior interaction map.” Zodiac provides molecular interactions for about 200 million pairs of genes. All the results are generated from a big-data analysis and organized into a comprehensive database allowing customized search. In addition, Zodiac provides data processing and analysis tools that allow users to customize the prior networks and update the genetic pathways of their interest. Zodiac is publicly available at www.compgenome.org/ZODIAC. Zodiac recapitulates and extends existing knowledge of molecular interactions in cancer. It can be used to explore novel gene-gene interactions, transcriptional regulation, and other types of molecular interplays in cancer.
Time and the implicit-explicit continuum
Authors: Jill Boucher
Journal: Behavioral and Brain Sciences (1999)

Dienes &amp; Perner's target article contains numerous but unsystematic references to the implicit or explicit knowledge of the temporal context of a known state of affairs such as may constitute the content of a propositional attitude. In this commentary, the forms of cognition that, according to D&amp;P, require only implicit knowledge of time are contrasted with those for which explicit temporal knowledge is needed. It is suggested that the explicit representation of time may have been important in human evolution and that certain developmental disorders including autism may be (partly) caused by defective ability to represent time.