tbuckley/cabot-search huggingface dataset:
Air pollution and health
Authors: M. Green
Journal: BMJ (1995)

The haze of photochemical smog that collects over cities has been seen by most people during hot summer spells. Media reports on adverse health effects abound, and in Britain last week the environment minister asked motorists to leave their cars at home. Is this wise advice or overreaction?

The fact that air pollution can be harmful has been accepted in Britain since 4000 excess deaths were recorded during the smog in December 1952.1 The public outcry that followed led to the Clean Air Act of 1957. Air quality improved to the extent that the Clean Air Council was abolished in 1979, the Medical Research Council's Air Pollution Unit was closed a year later, and the monitoring network was largely disbanded.

Classic industrial air pollution was made up largely of smoke and sulphur dioxide from the burning of coal and generally occurred in winter. In Britain this has mainly been replaced by pollution from the combustion of petrol and diesel, which predominantly takes place in vehicles. Vehicle exhausts emit oxides of nitrogen (particularly nitrogen dioxide), carbon monoxide, hydrocarbons, particulates, and lead. On hot, still days these accumulate over cities, together with low concentrations of industrial pollutants, and undergo further reactions catalysed …
Chemotherapy-Induced Neuropathy and Its Association With Quality of Life Among 2- to 11-Year Colorectal Cancer Survivors: Results From the Population-Based PROFILES Registry
Authors: Floortje Mols, Tonneke Beijers, Valery Lemmens, Corina J. van den Hurk, Gerard Vreugdenhil, Lonneke V. van de Poll-Franse
Journal: Journal of Clinical Oncology (2013)

Purpose To gain insight into the prevalence and severity of chemotherapy-induced neuropathy and its influence on health-related quality of life (HRQOL) in a population-based sample of colorectal cancer (CRC) survivors 2 to 11 years after diagnosis. Methods All alive individuals diagnosed with CRC between 2000 and 2009 as registered by the Dutch population-based Eindhoven Cancer Registry were eligible for participation. Eighty-three percent (n = 1,643) of patients filled out the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20. Results The five neuropathy subscale–related symptoms that bothered patients with CRC the most during the past week were erectile problems (42% of men), trouble hearing (11%), trouble opening jars or bottles (11%), tingling toes/feet (10%), and trouble walking stairs or standing up (9%). Additionally, patients who received oxaliplatin more often reported tingling (29% v 8%; P = .001), numbness (17% v 5%; P = .005), and aching or burning pain (13% v 6%; P = .03) in toes/feet compared with those not treated with chemotherapy. They also more often reported tingling toes/feet (29% v 14%; P = .0127) compared with those treated with chemotherapy without oxaliplatin. Those with many neuropathy symptoms (eg, upper 10%) reported statistically significant and clinically relevant worse HRQOL scores on all EORTC QLQ-C30 subscales (all P &lt; .01). Conclusion Two to 11 years after diagnosis of CRC, neuropathy-related symptoms are still reported, especially sensory symptoms in the lower extremities among those treated with oxaliplatin. Because neuropathy symptoms have a negative influence on HRQOL, these should be screened for and alleviated. Future studies should focus on prevention and relief of chemotherapy-induced neuropathy.
Pilot assessment of the response of several pulmonary hemodynamic variables to sublingual sildenafil in candidates for heart transplantation
Authors: Miguel Angel Gómez‐Sánchez, Carlos Saenz de la Calzada, Pilar Escribano Subías, Juan Francisco Delgado Jiménez, María Lázaro Salvador, Agustín Albarrán González, Luis Cea Calvo
Journal: European Journal of Heart Failure (2004)
Sequencing of LRP2 Reveals Multiple Rare Variants Associated with Urinary Trefoil Factor-3
Authors: Gearoid M. McMahon, Matthias Olden, Maija Garnaas, Qiong Yang, Xuan Liu, Shih-Jen Hwang, Martin G. Larson, Wolfram Goessling, Caroline S. Fox
Journal: Journal of the American Society of Nephrology (2014)

Novel biomarkers are being investigated to identify patients with kidney disease. We measured a panel of 13 urinary biomarkers in participants from the Offspring Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to 2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional studies in zebrafish were used to investigate histologic correlation with renal function. Across all 13 biomarkers, there were 97 significant SNPs at three loci. Lead SNPs at each locus were rs6555820 (P=6.7×10(-49); minor allele frequency [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788 (P=2.15×10(-16); MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and rs11048230 (P=4.77×10(-8); MAF=0.10) in an intergenic region near RASSF8 (associated with vascular endothelial growth factor). Validation in the CKDGen Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003). Sequencing of exons 16-72 of LRP2 in 200 unrelated individuals at extremes of urinary TFF3 levels identified 197 variants (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate testing, rare variants were associated with urinary TFF3 levels (P=0.003), and the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in zebrafish did not alter the renal phenotype in static or kidney injury models. In conclusion, this study revealed common variants associated with urinary levels of TFF3, kidney injury molecule-1, and vascular endothelial growth factor and identified a cluster of rare variants independently associated with TFF3.
Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families
Authors: A Balsa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied. <h3>PATIENTS AND METHODS</h3> From 1996 to 1998 European white families with at least two affected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were analysed. <h3>RESULTS</h3> 565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 affected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. Differences were found in disease duration (11–18 years) and in the prevalence of erosive disease (70–93%), nodules (15–44%), subjective Sjögren9s syndrome (5–38%), and EF (3–16%) (p&lt;0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE differed widely among countries (p&lt;0.0001): no SE alleles (6–36%), one allele (43–60%), and two alleles (20–39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient &lt;0.50) or in clinical and radiological features (κ&lt;0.22). <h3>CONCLUSIONS</h3> The differences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.
Male gonadal function in coeliac disease: 1. Sexual dysfunction, infertility, and semen quality
Authors: M J G Farthing, C R W Edwards, L H Rees, A M Dawson
Journal: Gut (1982)

The prevalence of hypogonadism, sexual dysfunction and abnormalities of semen quality was determined in 28 consecutive males with coeliac disease. These observations were related to jejunal morphology and nutritional status, and were compared with findings in 19 men with Crohn9s disease of similar age and nutritional status. Two of the 28 coeliacs (7%) had clinical evidence of hypogonadism but impotence and decreased sexual activity occurred more commonly, the latter apparently improving after gluten withdrawal. Of the married coeliacs, 19% had infertile marriages, a value greater than expected in the general population. Hypogonadism and sexual dysfunction were not detected in our patients with Crohn9s disease. Seminal analysis in coeliacs revealed marked abnormalities of sperm morphology and motility, but only the former appeared to improve after gluten withdrawal. Similar abnormalities, however, were also detected in patients with Crohn9s disease, although, unlike the coeliacs, 46% also had reduced concentrations of spermatozoa. Semen quality in coeliac disease could not be clearly related to general or specific (serum vitamin B<sub>12</sub> and red cell folate) nutritional deficiencies or to fertility, although sperm motility was markedly reduced in two of the three coeliacs with infertile marriages. The presence of antisperm antibodies did not appear to be an important aetiological factor in male infertility in coeliac disease. The pathogenesis of infertility and sexual dysfunction in coeliac disease remains unclear, suggesting that factors such as endocrine dysfunction or other specific nutritional deficiency may be involved.
Reduction of Elevated Plasma Osteopontin Levels With Resection of Non–Small-Cell Lung Cancer
Authors: Justin D. Blasberg, Harvey I. Pass, Chandra M. Goparaju, Raja M. Flores, Suzie Lee, Jessica S. Donington
Journal: Journal of Clinical Oncology (2010)

Purpose Plasma osteopontin (OPN) levels in advanced non–small-cell lung cancer (NSCLC) correlate with therapeutic response and survival, but the utility of plasma OPN for diagnosis and monitoring of early-stage NSCLC has not been investigated. We hypothesize that plasma OPN levels are elevated in early-stage NSCLC and decrease with resection. Patients and Methods Presurgery plasma OPN levels (in ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA) in a discovery set of 60 patients with early-stage NSCLC and were compared with data from 56 cancer-free smokers. Presurgery OPN was validated in an independent cohort of 96 patients with resectable NSCLC. The presurgery levels in the latter cohort were compared with matched postsurgery levels. Perioperative OPN levels were correlated with demographics, tumor characteristics, and perioperative events. OPN was monitored during follow-up. Results Discovery set presurgery NSCLC OPN (271 ± 31 ng/mL) was higher than smokers (40 ± 2 ng/mL; P = .001). Presurgery OPN was similar in the NSCLC validation cohort (324 ng/mL ± 20 ng/mL; P = .134). Postsurgery OPN (256 ng/mL ± 21 ng/mL) measured at mean of 9.8 weeks (range, 2 to 46 weeks) was lower than presurgery OPN (P = .005). Time from surgery significantly impacted postsurgery OPN: OPN ≤ 6 weeks postsurgery (303 n/mL ± 26 ng/mL) was higher than OPN greater than 6 weeks postsurgery (177 ng/mL ± 29 ng/mL; P = .003). Multivariate analysis noted correlations between albumin and creatinine to presurgery OPN and use of thoracotomy to postsurgery OPN. Recurrence rate was 5% at 29 weeks mean follow-up. OPN at recurrence was elevated from postsurgery nadir. Conclusion Plasma OPN levels are elevated in early-stage NSCLC. They are reduced after resection and appear to increase with recurrence. Plasma OPN may have utility as a biomarker in early-stage NSCLC.
CREB/PKA sensitive signalling pathways activate and maintain expression levels of the hepatitis B virus pre-S2/S promoter
Authors: F Tacke
Journal: Gut (2005)

<b>Background and aims:</b> CREB (cAMP response element binding protein) transcription factors are key regulators of homeostatic functions in the liver, and CRE binding is increased in hepatic inflammation. During chronic hepatitis B virus (HBV) infection, mutations or deletions in the pre-S region are frequently observed. These mutations can affect the pre-S2/S promoter controlling HBV envelope protein expression (hepatitis B surface antigen (HBsAg)) and have been associated with worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg expression. <b>Methods:</b> The effect of the CREB inducer protein kinase A (PKA) was tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter gene constructs were cloned to identify novel regulatory regions for the HBV pre-S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and supershift experiments were conducted to confirm DNA transcription factor binding. <b>Results:</b> Coexpression of HBV and PKA resulted in HBV-S mRNA induction and enhanced small envelope protein expression. We identified a CREB binding motif in the transcribed part of the pre-S2 region, contributing to basal S promoter activity via binding of activating transcription factor 2 (ATF2). A second CREB motif closely linked to the S-ATG showed a similar binding pattern involving ATF2 and CREB1, without appearing essential for basal promoter activity. Moreover, a sequence in the pre-S2 region is responsible for further transcriptional induction via CREB activators such as PKA and forskolin. EMSA experiments indicate that CREB1 and ATF4 are involved in complex formation conferring PKA dependent promoter activation. <b>Conclusions:</b> Our data suggest a novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of hepatocytes to enhance its HBsAg expression during homeostasis and hepatic inflammation.
Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload
Authors: V. Niederkofler
Journal: Journal of Clinical Investigation (2005)

Iron homeostasis plays a critical role in many physiological processes, notably synthesis of heme proteins. Dietary iron sensing and inflammation converge in the control of iron absorption and retention by regulating the expression of hepcidin, a regulator of the iron exporter ferroportin. Human mutations in the glycosylphosphatidylinositol-anchored protein hemojuvelin (HJV; also known as RGMc and HFE2) cause juvenile hemochromatosis, a severe iron overload disease, but the way in which HJV intersects with the iron regulatory network has been unclear. Here we show that, within the liver, mouse Hjv is selectively expressed by periportal hepatocytes and also that Hjv-mutant mice exhibit iron overload as well as a dramatic decrease in hepcidin expression. Our findings define a key role for Hjv in dietary iron sensing and also reveal that cytokine-induced inflammation regulates hepcidin expression through an Hjv-independent pathway.
NHS hospitals must become completely smoke free, says NICE
Authors: I. Torjesen
Journal: BMJ (2013)

Exchange protein directly activated by cAMP (Epac) and protein kinase A (PKA) are intracellular receptors for cAMP. Although PKA and its downstream effectors have been studied extensively in the context of drug addiction, whether and how Epac regulates cellular and behavioral effects of drugs of abuse remain essentially unknown. Epac is known to regulate AMPA receptor (AMPAR) trafficking. Previous studies have shown that a single cocaine exposure <i>in vivo</i> leads to an increase in GluA2-lacking AMPARs in dopamine neurons of the ventral tegmental area (VTA). We tested the hypothesis that Epac mediates cocaine-induced changes in AMPAR subunit composition in the VTA. We report that a single cocaine injection <i>in vivo</i> in wild-type mice leads to inward rectification of EPSCs and renders EPSCs sensitive to a GluA2-lacking AMPAR blocker in VTA dopamine neurons. The cocaine-induced increase in GluA2-lacking AMPARs was absent in Epac2-deficient mice but not in Epac1-deficient mice. In addition, activation of Epac with the selective Epac agonist 8-CPT-2Me-cAMP (8-CPT) recapitulated the cocaine-induced increase in GluA2-lacking AMPARs, and the effects of 8-CPT were mediated by Epac2. We also show that conditioned place preference to cocaine was impaired in Epac2-deficient mice and in mice in which Epac2 was knocked down in the VTA but was not significantly altered in Epac1-deficient mice. Together, these results suggest that Epac2 is critically involved in the cocaine-induced change in AMPAR subunit composition and drug-cue associative learning. <b>SIGNIFICANCE STATEMENT</b> Addictive drugs, such as cocaine, induce long-lasting adaptions in the reward circuits of the brain. A single intraperitoneal injection of cocaine leads to changes in the composition and property of the AMPAR that carries excitatory inputs to dopamine neurons. Here, we provide evidence that exchange protein directly activated by cAMP (Epac), a cAMP sensor protein, is required for the cocaine-induced changes of the AMPAR. We found that the effects of cocaine were mimicked by activation of Epac but were blocked by genetic deletion of Epac. Furthermore, cocaine-cue associative learning was impaired in mice lacking Epac. These findings uncovered a critical role of Epac in regulating the cellular and behavioral actions of cocaine.
Concurrent Disseminated Nocardiosis and GI Mucormycosis in a Stem-Cell Transplantation Recipient
Authors: Ming Y. Lim, Alisa P. Alker, Sophia Califano, Dimitri G. Trembath, Kevin Alby, Peter H. Gilligan, Katarzyna Jamieson, Jonathan S. Serody, Thomas C. Shea
Journal: Journal of Clinical Oncology (2014)
Abstract PR06: Lymphocyte invasion of basal breast tumors is associated with wild-type p53
Authors: David A. Quigley, Charlie Vaske, Laxmi Silwa-Pandit, Ruth Dannenfelser, Anita Langerød, Hans Kristian M. Vollan, Olga Troyanskaya, Suet-Feung Chin, Carlos Caldas, Allan Balmain, Anne-Lise Børresen-Dale, Vessela Kristensen
Journal: Cancer Research (2015)

Abstract The tumor suppressor p53 is mutated in approximately 30% of breast adenocarcinomas, but the clinical implications of p53 mutation depend on the subtype of breast tumor. Although p53 mutation is associated with worse outcome for patients with Luminal B and Her2 subtypes, the same is not true in Basal tumors, despite the fact that Basal tumors have the highest frequency of p53 mutation of any subtype. Lymphocytic infiltration is associated with better prognosis in several epithelial malignancies including triple-negative breast tumors. In this study we identify an association in Basal breast cancer between lymphocytic infiltration and the number of copies of wild-type p53 by combining gene expression, p53 sequencing, DNA copy number analysis, and semi-quantitative immune cell histology in 1,281 tumors. We use the Nanodissect algorithm to define signatures for T cell types and show that the infiltration consists primarily of cytotoxic T lymphocytes. Elevated expression of this gene signature is associated with better outcome in Basal tumors, and differential pathway activity analysis identifies significant activation of caveolin 1 signaling to TGF-beta in p53 wild-type Basal tumors. These findings identify a new link between the p53 pathway and beneficial adaptive immune response in breast tumors not responsive to the estrogen receptor, supporting a connection between a lack of p53 function and the failure of tumor immunosurveillance. This abstract is also presented as Poster A35. Citation Format: David A. Quigley, Charlie Vaske, Laxmi Silwa-Pandit, Ruth Dannenfelser, Anita Langerød, Hans Kristian M. Vollan, Olga Troyanskaya, Suet-Feung Chin, Carlos Caldas, Allan Balmain, Anne-Lise Børresen-Dale, Vessela Kristensen. Lymphocyte invasion of basal breast tumors is associated with wild-type p53. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR06. doi:10.1158/1538-7445.CHTME14-PR06
The Role of Prevention in Oncology Practice: Results From a 2004 Survey of American Society of Clinical Oncology Members
Authors: Patricia A. Ganz, Lorna Kwan, Mark R. Somerfield, David Alberts, Judy E. Garber, Kenneth Offit, Scott M. Lippman
Journal: Journal of Clinical Oncology (2006)

In 2004, the American Society of Clinical Oncology (ASCO) Cancer Prevention Committee surveyed the members to describe involvement in clinical prevention activities.A previously administered survey, with updated items on genetics, chemoprevention, and survivorship, was mailed to a stratified random sample of 2,000 domestic members and a convenience sample of 3,144 international members.A total of 49.7% of domestic members contacted and survey eligible responded (n = 851). Nonresponders were younger (50.5 v 51.7 years; P < .01); 465 international members responded. Overall, 35% had received formal instruction in cancer prevention and control, and most respondents expected increased use of prevention, screening/early detection, and risk reduction/genetic counseling in their practices in the next 5 years. Most reported caring for cancer survivors, including providing general medical care. They also either directly provide or refer patients for cancer prevention and control services (eg, cancer screening, tobacco and nutrition counseling, risk reduction, and chemoprevention). Multivariable modeling found fewer perceived barriers to inclusion of cancer prevention activities in clinical practice among those practicing in an academic setting, seeing a higher proportion of patients without a cancer diagnosis, having formal training in prevention and control, expecting an increase in prevention activities in the next 5 years, and providing community advice on prevention.Barriers to the inclusion of cancer prevention and control activities in oncology clinical practice exist. Nevertheless, a substantial proportion of both domestic and international ASCO members report an interest in cancer prevention and control activities, with a desire for more specific educational programs in this emerging area of oncology practice.