tbuckley/cabot-search huggingface dataset:
Sources of Fine Particulate Matter and Risk of Preterm Birth in Connecticut, 2000–2006: A Longitudinal Study
Authors: Gavin Pereira, Michelle L. Bell, Hyung Joo Lee, Petros Koutrakis, Kathleen Belanger
Journal: Environmental Health Perspectives (2014)

Background: Previous studies have examined fine particulate matter (≤ 2.5 μm; PM2.5) and preterm birth, but there is a dearth of longitudinal studies on this topic and a paucity of studies that have investigated specific sources of this exposure.Objectives: Our aim was to assess whether anthropogenic sources are associated with risk of preterm birth, comparing successive pregnancies to the same woman.Methods: Birth certificates were used to select women who had vaginal singleton live births at least twice in Connecticut during 2000–2006 (n = 23,123 women, n = 48,208 births). We procured 4,085 daily samples of PM2.5 on Teflon filters from the Connecticut Department of Environmental Protection for six cities in Connecticut. Filters were analyzed for chemical composition, and Positive Matrix Factorization was used to determine contributions of PM2.5 sources. Risk estimates were calculated with conditional logistic regression, matching pregnancies to the same women.Results: Odds ratios of preterm birth per interquartile range increase in whole pregnancy exposure to dust, motor vehicle emissions, oil combustion, and regional sulfur PM2.5 sources were 1.01 (95% CI: 0.93, 1.09), 1.01 (95% CI: 0.92, 1.10), 1.00 (95% CI: 0.89, 1.12), and 1.09 (95% CI: 0.97, 1.22), respectively.Conclusion: This was the first study of PM2.5 sources and preterm birth, and the first matched analysis, that better addresses individual-level confounding potentially inherent in all past studies. There was insufficient evidence to suggest that sources were statistically significantly associated with preterm birth. However, elevated central estimates and previously observed associations with mass concentration motivate the need for further research. Future studies would benefit from high source exposure settings and longitudinal study designs, such as that adopted in this study.Citation: Pereira G, Bell ML, Lee HJ, Koutrakis P, Belanger K. 2014. Sources of fine particulate matter and risk of preterm birth in Connecticut, 2000–2006: a longitudinal study. Environ Health Perspect 122:1117–1122; http://dx.doi.org/10.1289/ehp.1307741
MicroRNAs Play a Big Role in Regulating Ovarian Cancer–Associated Fibroblasts and the Tumor Microenvironment
Authors: Jonathan Chou, Zena Werb
Journal: Cancer Discovery (2012)

Abstract Summary: Mitra and colleagues analyzed microRNA expression profiles of fibroblasts isolated from ovarian cancer patients, searching for dysregulated microRNAs in the stromal compartment of human cancer. They found that decreased miR-31 and miR-214 and increased miR-155 expression can reprogram normal fibroblasts into tumor-promoting cancer-associated fibroblasts. They identified CCL5, a protumorigenic chemokine that is highly expressed in tumors, as a key target of miR-214, thus showing that microRNA perturbation in the stromal microenvironment can affect tumor growth. Cancer Discov; 2(12); 1078–80. ©2012 AACR. Commentary on Mitra et al., p. 1100
Genetic variants in the MRPS30 region and postmenopausal breast cancer risk
Authors: Ying Huang, Dennis G Ballinger, James Y Dai, Ulrike Peters, David A Hinds, David R Cox, Erica Beilharz, Rowan T Chlebowski, Jacques E Rossouw, Anne McTiernan, Thomas Rohan, Ross L Prentice
Journal: Genome Medicine (2011)

Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest.We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction.The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343.Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.
Analysis of RAG expression by peripheral blood CD5+ and CD5- B cells of patients with childhood systemic lupus erythematosus
Authors: H Morbach
Journal: Annals of the Rheumatic Diseases (2005)

The assembly of immunoglobulin genes during B cell development in the bone marrow is dependent on the expression of recombination activating genes (RAG) 1 and 2. Recently, RAG expression in peripheral blood IgD+ B cells outside the bone marrow has been demonstrated and is associated with the development of autoimmune diseases.To investigate RAG expression in the CD5+ or CD5- IgD+ B cell compartment in childhood systemic lupus erythematosus (SLE).Using a combination of flow cytometric cell sorting and reverse transcriptase polymerase chain reaction analysis of cDNA libraries generated from individual cells, the expression of RAG, VpreB, and CD154 mRNA by individual peripheral blood B cells of three paediatric SLE patients was examined in detail.While only one patient had a significantly increased frequency of RAG+ B cells in the CD5- B cell population, all patients showed higher frequencies of RAG+ B cells in the CD5+IgD+ B cell population. The frequency of RAG+ IgD+CD5+/- B cells was reduced during intravenous cyclophosphamide treatment. In healthy age matched children, RAG expressing IgD+ B cells were hardly detectable. Coexpression of RAG and VpreB or CD154 mRNA could only be found in SLE B cells.RAG expression in peripheral blood B cells of SLE patients is particularly increased in the IgD+CD5+ B cell population. CD5+ and CD5- B cells in SLE have the potential to undergo receptor revision leading to the generation of high affinity pathogenic autoantibodies.
Human intermittent hypoxia-induced respiratory plasticity is not caused by inflammation
Authors: Andrew E. Beaudin, Xavier Waltz, Matiram Pun, Katherine E. Wynne-Edwards, Sofia B. Ahmed, Todd J. Anderson, Patrick J. Hanly, Marc J. Poulin
Journal: European Respiratory Journal (2015)

Ventilatory instability, reflected by enhanced acute hypoxic (AHVR) and hypercapnic (AHCVR) ventilatory responses is a fundamental component of obstructive sleep apnoea (OSA) pathogenesis. Intermittent hypoxia-induced inflammation is postulated to promote AHVR enhancement in OSA, although the role of inflammation in intermittent hypoxia-induced respiratory changes in humans has not been examined. Thus, this study assessed the role of inflammation in intermittent hypoxia-induced respiratory plasticity in healthy humans. In a double-blind, placebo-controlled, randomised crossover study design, 12 males were exposed to 6 h of intermittent hypoxia on three occasions. Prior to intermittent hypoxia exposures, participants ingested (for 4 days) either placebo or the nonsteroidal anti-inflammatory drugs indomethacin (nonselective cyclooxygenase (COX) inhibitor) and celecoxib (selective COX-2 inhibitor). Pre- and post-intermittent hypoxia resting ventilation, AHVR, AHCVR and serum concentration of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α were assessed. Pre-intermittent hypoxia resting ventilation, AHVR, AHCVR and TNF-α concentrations were similar across all three conditions (p≥0.093). Intermittent hypoxia increased resting ventilation and the AHVR similarly across all conditions (p=0.827), while the AHCVR was increased (p=0.003) and TNF-α was decreased (p=0.006) with only selective COX-2 inhibition. These findings indicate that inflammation does not contribute to human intermittent hypoxia-induced respiratory plasticity. Moreover, selective COX-2 inhibition augmented the AHCVR following intermittent hypoxia exposure, suggesting that selective COX-2 inhibition could exacerbate OSA severity by increasing ventilatory instability.
Detection of Isolated Tumor Cells by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism for K-ras Mutations in Tissue Samples of 199 Colorectal Cancer Patients
Authors: Christoph P. Dieterle, Michael Conzelmann, Ulrich Linnemann, Martin R. Berger
Journal: Clinical Cancer Research (2004)

Abstract The aim of this study was to identify K-ras mutations as marker for isolated tumor cells in liver, lymph node, and bone marrow specimens of colorectal cancer patients. To detect these, a PCR-RFLP assay was used with a sensitivity exceeding that of routine histopathology by at least 1 order of magnitude. In addition, the ratio of mutated versus wild-type alleles was determined by an internal standard. Of 199 patients, 74 (37.5%) were found to bear a K-ras-positive tumor. Of these, 60 (81%) were mutated in codon 12 and 14 (19%) in codon 13 (P &amp;lt; 0.001). In addition, 14 organs were found K-ras positive, 13 of which were from 12 patients with a K-ras-positive tumor (16%) and 1 from a patient with a K-ras-negative tumor (0.8%). Eight patients exhibited liver involvement and 6 showed lymph node involvement. Remarkably, no bone marrow specimen was found K-ras positive (P &amp;lt; 0.017 versus liver involvement). Sequence analysis of tumor DNA revealed that GGT (Gly) was replaced by GAT (Asp; 35%), GTT (Val; 32%), AGT (Ser; 13%), GCT (Ala; 10%), TGT (Cys; 8%), and CGT (Arg; 2%) for codon 12, and by GAC (Asp) as the only type of mutation for codon 13. In colorectal carcinomas the ratio of K-ras mutated versus wild-type alleles ranged over 4 orders of magnitude (100-10−4, median: 10−2) and was correlated with both, residual tumor load (R1/2; P = 0.028) and distant metastasis (M1; P = 0.057). These results show that detection of K-ras mutated alleles by PCR-RFLP in patients with colorectal carcinoma may aid in the identification of isolated tumor cells. High ratios of K-ras alleles were correlated with certain negative prognostic parameters (R,M). In accord with its function as a primary filter for colorectal carcinoma cells, the liver was more often contaminated with K-ras-positive cells than bone marrow.
Risk of Leukemia Following Treatment for Non-Hodgkin's Lymphoma
Authors: L. B. Travis, R. E. Curtis, M. Stovall, E. J. Holowaty, F. E. van Leeuwen, B. Glimelius, C. F. Lynch, A. Hagenbeek, C.-Y. Li, P. M. Banks, M. K. Gospodarowicz, J. Adami, S. Wacholder, P. D. Inskip, M. A. Tucker, J. D. Boice
Journal: JNCI Journal of the National Cancer Institute (1994)

There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described.Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL.Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls.Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy.Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.
‘Biologics’: a clinically meaningless term
Authors: Kenneth A. Katz
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Anton Inbedkov:Shall we say ‘pistols at dawn'? Boris Grushenko:Well, we can say it. I don't know what it means, but we can say it. —From Woody Allen's Love and Death (1975).1 ‘Biologics’ have become ubiquitous in dermatology. We read about them in our journals, hear about them at our meetings, meet their salespeople in our offices, see their promotional materials everywhere, receive countless invitations to participate in continuing medical education (CME) courses and dinner talks focusing on them, and – increasingly – prescribe them for our patients. Similarly, the term ‘biologics’ has become pervasive in the dermatology lexicon. (Full disclosure: I've used the term myself in the past.)2 But do we really know what we mean when we use the term? I suggest that the term ‘biologics’ actually has as much relevance to clinical dermatologists as the phrase ‘pistols at dawn’ had to Grushenko – which is to say, none at all. Moreover, to the extent that the term ‘biologics’ has meaning to clinical dermatologists, it only misleads us.
Effect of bisphosphonates on cartilage turnover assessed with a newly developed assay for collagen type II degradation products
Authors: H J Lehmann
Journal: Annals of the Rheumatic Diseases (2002)

Background: Animal studies of arthritis have suggested that bisphosphonates may have chondroprotective abilities. Objective: To evaluate the effect of bisphosphonate treatment on cartilage degradation. Methods: Type II collagen is almost exclusively localised in cartilage, where it is the major structural component of the tissue. Hence fragments derived from this protein should represent a specific index for cartilage degradation. The urinary concentration of collagen type II C-telopeptide degradation products (CTX-II) was measured by a new immunoassay (enzyme linked immunosorbent assay (ELISA)). The serum concentration of collagen type I C-telopeptide degradation products (CTX-I), a marker of bone degradation, was also measured by ELISA. Participants: Two groups were studied. The alendronate group included 63 healthy postmenopausal women aged 45–54 randomly allocated to receive three years9 treatment with 1 mg, 5 mg, 10 mg, or 20 mg alendronate daily or placebo. In the third year the women receiving 20 mg were switched to placebo. The ibandronate group included 119 women at least 10 years after the menopause aged &lt;75 randomly allocated to receive 12 months9 treatment with 0.25 mg, 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg ibandronate daily or placebo followed by 12 months without treatment. Results: 20 mg of alendronate and 2.5 and 5 mg of ibandronate treatment produced significant decreases in urinary CTX-II to about 50% of baseline. The level reached after three months of treatment remained practically constant during the following 12–36 treatment months. When treatment was withdrawn CTX-II values returned towards baseline. Serum CTX-I also decreased rapidly within three months, but to a level of about 30% of baseline. Conclusions: The urinary excretion of CTX-II, a new marker of cartilage degradation, decreases significantly in response to bisphosphonate. This suggests that bisphosphonates may have chondroprotective effects in humans. By measurement of CTX-II it should be possible to monitor the effects of drugs that potentially inhibit cartilage destruction.
Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony
Authors: Maria Vittoria Pitzalis, Massimo Iacoviello, Roberta Romito, Francesco Massari, Brian Rizzon, Giovanni Luzzi, Pietro Guida, Andrea Andriani, Filippo Mastropasqua, Paolo Rizzon
Journal: Journal of the American College of Cardiology (2002)
Abstract 3830: E2F1-FOXM1 activation predicts progression of non-muscle invasive bladder cancer
Authors: Seon-Kyu Kim, Se-Ra Lee, Yun-Gil Roh, Bicna Song, Kiejung Park, Sun-Hee Leem, In-Sun Chu
Journal: Cancer Research (2014)

Abstract Backgrounds: Bladder cancer is a genetic disorder driven by the accumulative changes of the multiple genes, such as E2F1, FOXM1, and EZH2. The objective of this study is to estimate a prognostic value of gene expression signature and identify putative signaling pathway for mediating progression of non-muscle invasive bladder cancer (NMIBC). Methods: Gene expression profiling was performed using primary NMIBC cohort to identify a signature correlated with disease progression. The signature was validated in three independent cohorts. The association between the signature and prognosis of NMIBC patients was assessed using various statistical methods including a leave-one-out cross-validation and multivariate Cox regression analyses. The upstream regulator analysis of the genes in the signature was performed by Ingenuity Pathway Analysis TM. We also confirmed a prognostic relevance of the signature with experimental assays using bladder cancer cell lines. Results: Kaplan-Meier analysis in the discovery cohort revealed significant differences in disease progression associated with the expression signature of E2F1-associated genes (p = 0.003), which produced consistent prognostic pattern in the validation cohorts. Multivariate Cox regression analysis revealed that the signature was an independent strong predictor of disease progression (hazard ratio = 6.082, 95% confidence interval = 3.280 to 11.279, p &amp;lt; 0.001). In subset analyses, the signature could identify patients who would benefit from intravesical immunotherapy. Lastly, upstream regulator analyses and experimental assays of the signature revealed that NMIBC progression could be mediated by E2F1-FOXM1 pathways. Conclusion: The prognostic molecular signature defined by activation of E2F1 and FOXM1 represents a promising diagnostic tool to identify high risk NMIBC patients. Citation Format: Seon-Kyu Kim, Se-Ra Lee, Yun-Gil Roh, Bicna Song, Kiejung Park, Sun-Hee Leem, In-Sun Chu. E2F1-FOXM1 activation predicts progression of non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3830. doi:10.1158/1538-7445.AM2014-3830
Developmental origins of health and disease: reducing the burden of chronic disease in the next generation
Authors: Peter D Gluckman, Mark A Hanson, Murray D Mitchell
Journal: Genome Medicine (2010)

Despite a wealth of underpinning experimental support, there has been considerable resistance to the concept that environmental factors acting early in life (usually in fetal life) have profound effects on vulnerability to disease later in life, often in adulthood. This has resulted in an unwillingness among public health decision makers to implement relatively simple approaches, based upon an understanding of developmental plasticity and intergenerational influences, to reducing the burden of disease particularly in low socioeconomic groups.
Doxorubicin With Cyclophosphamide Followed by Docetaxel Every 21 Days Compared With Doxorubicin and Docetaxel Every 14 Days As Preoperative Treatment in Operable Breast Cancer: The GEPARDUO Study of the German Breast Group
Authors: Gunter von Minckwitz, Günter Raab, Angelika Caputo, Martin Schütte, Jörn Hilfrich, Jens U. Blohmer, Bernd Gerber, Serban D. Costa, Elisabeth Merkle, Holger Eidtmann, Dieter Lampe, Christian Jackisch, Andreas du Bois, Manfred Kaufmann
Journal: Journal of Clinical Oncology (2005)

Purpose Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer. Methods This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m 2 plus docetaxel 75 mg/m 2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m 2 plus cyclophosphamide 600 mg/m 2 every 21 days followed by docetaxel 100 mg/m 2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes. Secondary end points were predictors for pCR, clinical response, rate of breast conservation, and safety. Results A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with ADOC (7.0%; n = 31) (odds ratio, 2.22; 90% CI, 1.52 to 3.24; P &lt; .001). Independent predictors of attaining a pCR included the use of sequential therapy, high tumor grade, and negative hormone receptor status. The response rates detected by palpation and by imaging were significantly higher with AC-DOC (85.0% and 78.6%, respectively) than with ADOC (75.2% and 68.6%, respectively; both P values &lt; .001). The rate of breast-conserving surgery was 63.4% for AC-DOC and 58.1% for ADOC (P = .05). Predominant grade 3/4 toxicities were leucopenia (AC-DOC, 74.2%; ADOC, 53.7%) and neutropenia (AC-DOC, 66.4%; ADOC, 44.7%) but were infrequently associated with fever (AC-DOC, 4.6%; ADOC, 3.1%). Conclusion Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer.