tbuckley/cabot-search huggingface dataset:
AB0446 A comparative study of quantiferon TB-2G and 3G as screening examination for latent mycobacterium tuberculosis infection in patients with rheumatoid arthritis before treatment with biologics
Authors: Y. Hirano, Y. Oishi, T. Mieno, K. Yamauchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Mycobacterium Tuberculosis (TB) infection is one of the typical adverse events during the treatment with biologics, especially anti-tumour necrosis factor (TNF) agents, in patients with rheumatic disease. The screening of latent TB infection before treatment with biologics is recommended in a lot of recommendations including ACR recommendation and recommendation in European countries. Several methods of screening latent TB infection are used in clinical practice and QuantiFERON (QFT) is one of them. Although QFT-2G was old type, QFT-3G was newly developed. Differences in characters between these two methods are not well understood. <h3>Objectives</h3> The objectives of this study are to compare QFT-2G and 3G as screening for latent TB infection in patients with rheumatoid arthritis (RA) before treatment with biologics and investigate the outcome after initiation of biologics treatment. <h3>Methods</h3> RA patients in whom QFT-2G or 3G was performed in our department were included in this study. Patient characteristics and result of QFT were compared between 2G group and 3G group. Chest CT findings and clinical course after initiation of biologics were investigated in patients with positive QFT. <h3>Results</h3> 178 cases and 57 cases were included in 2G group and 3G group, respectively. Mean age in 2G group and 3G group were 59.3 years old and 60.4 years old, respectively. 5 cases in 2G group have past history of TB infection and none in 3G group. 5 cases in 2G group (2.8%) and 6 cases in 3G group (10.5%) have positive results and there was a significant difference (p=0.027). 157 cases in 2G group (88.2%) and 42 cases in 3G group (73.7%) have negative results and there was a significant difference (p=0.011). In 10 cases that had positive results of QFT 2G or 3G, none had past history of TB, chest CT was normal in 4 cases and chemoprophylaxis of isoniazid (INH) was performed in 5 cases. Although biologics was used in 7 cases among 10 QFT-positive cases, no active TB was occurred until last observation. Used biologics were infliximab in 2 cases, etanercept in a case, abatacept in 3 cases and golimumab in a case. <h3>Conclusions</h3> Although higher positive rate and lower negative rate were seen in QFT-3G group compared with in QFT-2Ggroup, its usefulness in clinical practice is unknown. QFT-3G has high sensitivity and patients who were prescribed with INH are increased. There are several adverse events including hepatic toxicity in INH chemoprophylaxis. This study suggested that biologics therapy with INH chemoprophylaxis was acceptable in RA patients with positive QFT if they had no findings of suspected active TB in clinical sign or chest X-P and CT. <h3>Disclosure of Interest</h3> None Declared
Intellectual Impairment in Children Exposed to Polychlorinated Biphenyls in Utero
Authors: Joseph L. Jacobson, Sandra W. Jacobson
Journal: New England Journal of Medicine (1996)

In utero exposure to polychlorinated biphenyls, a ubiquitous environmental contaminant, has been linked to adverse effects on neurologic and intellectual function in infants and young children. We assessed whether these effects persist through school age and examined their importance in the acquisition of reading and arithmetic skills.
P04 A dose effect of the disease risk gene HLA DR3 contributes to numerical and functional impairment of CD4+CD25+ regulatory T cells in patients with autoimmune hepatitis
Authors: P. Wang, J. Underhill, M. S. Longhi, G. Mieli-Vergani, Y. Ma, D. Vergani
Journal: Gut (2011)

<h3>Introduction</h3> Autoimmune diseases are frequent among first degree relatives (FDR) of patients with autoimmune hepatitis (AIH), but concordance for AIH is rare. A numerical and functional impairment of CD4<sup>pos</sup>CD25<sup>pos</sup> regulatory T cells (Tregs) is described in AIH patients, but no study has addressed Treg status in their FDR. <h3>Aim</h3> To define whether the defect of Tregs in AIH is inherited and is associated with disease predisposing HLA genes. <h3>Method</h3> 44 children with AIH (33 AIH-1 and 11 AIH-2, median age 13.5 yrs, 23 females), 65 FDR from 34 families [23 fathers, 47 yrs (38–58); 28 mothers, 44 yrs (24–53) and 14 siblings, 7 females, 13 yrs (5–24)] and 42 healthy subjects [HS, 36 yrs (22–54), 37 females] were studied. Tregs were purified from PBMCs using immunomagnetic beads and their phenotype and frequency was assessed by flowcytometry. CD25<sup>neg</sup> cells were used as responders in co-culture with Tregs and their proliferation was measured by <sup>3</sup>H-thymidine incorporation. HLA genotyping was performed by PCR using gene specific primers. <h3>Results</h3> The frequency of the disease predisposing gene HLA DR3 was significantly higher in patients (71%) and their FDR (56%) than in HS (23%, p&lt;0.0001 and p&lt;0.005). The frequency of homozygous DR3 was higher in patients (29%) than in FDR (9%, p=0.015) and HS (0%, p=0.001). In patients the frequency of HLA A1-B8-DR3 haplotype (42%) was higher than in FDR (27%, p=0.15) and HS (16%, p=0.02). The frequency of conventional CD4<sup>pos</sup>CD25<sup>pos</sup> Tregs was lower in patients (6.2%±0.5) than in FDR (9.3%±0.7, p=0.0016) and HS (9.7%±0.8, p=0.001). Though the frequency of CD4<sup>pos</sup>CD25<sup>high</sup>CD127<sup>neg</sup> ‘True’ Tregs was similar among patients, FDR and HS (6.0%±0.6, 6.3%±0.4 and 6.2%±0.5), their suppressive function was lower in patients (13.6% reduction of CD25<sup>neg</sup> cell proliferation) than in FDR (28.8%, p=0.007) and HS (36.9%, p&lt;0.0001). Among subjects positive for HLA DR3, the frequency of conventional Tregs was lower in patients (5.6%±0.5) than in FDR (8.4%±0.97, p=0.01) and in HS (9.1%±1.4, p=0.006). Among subjects positive for HLA A1-B8-DR3 haplotype, the frequency of Tregs was lower in patients (6.0%±0.7) than in FDR (9.1%±1.5, p=0.045) and HS (9.8%±1.8, p=0.02). <h3>Conclusion</h3> A numerical and functional impairment of Tregs in AIH patients is associated with possession of HLA disease predisposing genes, and in particular HLA DR3 homozygosity. Possession of DR3 was not associated to a similar immune regulatory impairment in FDR and HS, suggesting that a gene dose effect contributes to the impairment of immunoregulation and to the development of AIH.
Medicare Coverage of Mammograms Focus of Mother's Day Campaign
Authors: M. K. Taylor
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Medicare Coverage of Mammograms Focus of Mother's Day Campaign Get access Melissa Kraus Taylor Melissa Kraus Taylor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 10, 17 May 1995, Page 719, https://doi.org/10.1093/jnci/87.10.719 Published: 17 May 1995
Abstract 1947: Identification of microRNAs that regulate DNA damage response
Authors: Yemin Wang, Toshiyasu Taniguchi
Journal: Cancer Research (2010)

Abstract Mammalian cells have developed an elaborate DNA damage response system and DNA repair machinery, which play a critical role in the prevention of cancer and development of resistance to anti-cancer DNA damaging agents. Many proteins involved in DNA damage response, such as phosphorylated histone H2AX (γH2AX) and 53BP1, form nuclear foci at sites of DNA damage and facilitate DNA damage response and repair. The precise regulation of DNA damage response is crucial for cellular survival after DNA damage and its abrogation often results in genomic instability. MicroRNAs (miRNAs) are short, non-coding RNA molecules, which post-transcriptionally regulate gene expression by repressing translation and/or degrading mRNA. Some miRNAs function as oncogenes or tumor suppressors. However, the role of miRNAs in DNA damage response remains largely unknown. Here, we identified miRNAs that regulate DNA damage response, especially γH2AX/53BP1 foci formation, and modulate chemo-/radio-sensitivity of tumor cells. We developed a cell-based screening assay utilizing ionizing radiation (IR)-induced γH2AX/53BP1 foci formation in a human osteosarcoma cell line, U2OS, as a readout. The human miRNA Mimics and Inhibitors Libraries (Dharmacon), consisting of 810 miRNA mimics or inhibitors, were transfected in U2OS cells and screened with an automated high-throughput fluorescence microscope and an automatic foci counter. We found that two and five miRNA mimics reproducibly inhibited IR-induced γH2AX and 53BP1 foci formation, respectively, while none of the miRNA inhibitors inhibited their foci formation. Among these hits, we focused on miR-138, because miR-138 is reported to be deregulated in a subset of cancer and may be involved in tumorigenesis and chemosensitivity of cancer. We found that miR-138 decreased the expression of H2AX and reduced H2AX phosphorylation upon DNA damage. Consistent with a defect in DNA damage response, miR-138 sensitized U2OS cells to DNA damaging agents, such as IR and cisplatin. Importantly, the 3′UTR of H2AX contains a putative miR-138 binding site, suggesting that H2AX may be a direct target of miR-138. Taken together, we have identified some miRNAs which inhibit IR-induced foci formation of γH2AX/53BP1. In particular, miR-138 strongly reduced H2AX-mediated DNA damage response and enhanced the chemo-/radio-sensitivity of cancer cells, suggesting that miR-138 might serve as an important regulator of genome instability and a possible therapeutic target for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1947.
P286 Recommendations For Smoking Cessation Service Provision For Smokers With Copd With Multiple Complex Needs: Findings From A Pilot Study
Authors: S. Yap, E. Pang, S. Lunn, C. Croft, M. Stern
Journal: Thorax (2014)

<h3>Introduction</h3> Smokers with COPD are highly nicotine addicted and often have additional complex needs. Quit rates are poor and there is little evidence-based guidance on specific cessation interventions for these patients. This pilot study aimed to identify barriers to smoking cessation for this patient group. <h3>Method</h3> Smokers with COPD were offered up to 12 individual sessions with a clinical psychologist in addition to standard smoking cessation counselling and pharmacotherapy. The psychological intervention included an initial assessment and formulation on factors maintaining smoking which informed an individualised psychology intervention targeting barriers to smoking cessation. <h3>Results</h3> 57 patients (moderate COPD, high prevalence of complex physical andpsychological comorbidities) were included in the study (Table 1). 20/57 (35%) patients attended &gt;2 sessions (mean=5, range 2–12). 7/20 had already quit (relapse prevention referrals), 13 were smokers. 22/57 (39%) patients never engaged, 15/57 (26%) were lost to follow-up. 6/7 (86%) of the relapse prevention group maintained their quit. 2/13 (15%) of the current smoker group maintained a 28 day quit and 4/13 (31%) reduced tobacco intake. Psychological barriers to quitting were identified including smoking as a means of emotion regulation. <h3>Conclusions</h3> For COPD smokers with a heavy smoking history and multiple quit attempts, and complex needs, additional psychological intervention alongside traditional quit smoking support may aid in preventing relapse, although further research is needed. For current smokers, the hypothesis was not supported, although the study did illuminate common themes regarding obstacles to quitting for this complex group who present a challenge to traditional quit smoking services. It is clear that the current ‘one size fits all’ approach to smoking cessation does not meet the needs of these smokers who require more focused specific interventions to support smoking cessation including: Pre-quit support ‘Cut down to quit’ approach Long-term, intensive follow up Assertive outreach Multi-agency working The above recommendations may provide a starting point for future service design.
PROCEDURAL BENEFIT OF SUBSTRATE BASE ABLATION VERSUS CONVENTIONAL MAPPING AND ABLATION OF CLINICAL STABLE VENTRICULAR TACHYCARDIA: RESULTS FROM THE VISTA RANDOMIZED TRIAL
Authors: Luigi Di Biase, John Burkhardt, Dhanunjaya Lakkireddy, Corrado Carbucicchio, Sanghamitra Mohanty, Chintan Trivedi, Prasant Mohanty, Pasquale Santangeli, Rong Bai, Giovanni Forleo, Rodney Horton, Shane Bailey, Javier Sanchez, Amin Al-Ahmad, Patrick Hranitzky, Gemma Pelargonio, Richard Hongo, Salwa Beheiry, Steven Hao, Madhu Reddy, Antonio Rossillo, Sakis Themistoclakis, Antonio Dello Russo, Claudio Tondo, Andrea Natale
Journal: Journal of the American College of Cardiology (2015)
Abstract 3385A: Synergistic effect of purified components from Antrodia Cinnamomea Mycelia on targeting oral cancer stem cell
Authors: Ching-Wen Chang, Jeng-Fan Lo
Journal: Cancer Research (2012)

Abstract Background: Cancer stem cells (CSCs), also termed as Cancer initiating cells (CICs), represent a rare subpopulation of cells, which are responsible for tumor growth. CICs such as oral cancer -cancer initiating cells (OC-CICs), are often resistant to either radio- or chemotherapy. Therefore, development of drug candidates that specifically target OC-CICs will be effective for future oral cancer therapy. Methods: In this study, we used the in vitro cell-based ALDH activity assay system, which has been demonstrated as a CICs marker, to screen for the active purified components from Antrodia Cinnamomea Mycelia extract (ACME), which can target OC-CICs. In combination with the active components from ACME that targeting OC-CICs, we evaluated the synergistic effect of above active components from ACMS on target oral cancer stem cells. Results: We first found ACME purified compounds (CH-190-WS-A and CH-190-WS-D) can significantly down regulate the ALDH activity of oral cancer cells or OC-CICs, respectively. Treatment of CH-190-WS-A and CH-190-WS-D significantly induced cell death and enhanced the differentiation capability of OC-CICs. Moreover, we found that treatment of CH-190-WS-A and CH-190-WS-D reduced the self-renewal ability, tumorigenic properties and stemness properties of OC-CICs in vitro. Additionally, treatment with CH-190-WS-A or CH-190-WS-D suppressed tumor growth of nude mice bearing tumor xenografts, respectively. Furthermore, treatment of CH-190-WS-D results in down-regulation of mTOR/PI3K/pAKT molecular mechanisms which play an important role in CICs. Whereas treatment of CH-190-WS-A inactivated Notch pathway, which can restore AKT activity then overcome cell death. Finally, combined treatment of CH-190-WS-D and CH-190-WS-A also dramatically caused cell death of OC-CICs through dual-pathway blockage. Conclusion: Our studies reveal combination of ACME purified components can target OC-CICs. Eventually, we can develop therapeutic protocol for alternative oral cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3385A. doi:1538-7445.AM2012-3385A
CORONARY ARTERY CALCIUM SCORE IS SUPERIOR TO CAROTID PLAQUE SCORE FOR PREDICTING CARDIOVASCULAR DISEASE EVENTS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Adam D. Gepner, Rebekah Young, Joel Kaufman, Joseph Delaney, Michael Blaha, Wendy Post, Erin Michos, Joseph Polak, James Stein
Journal: Journal of the American College of Cardiology (2016)
Abstract PD02-03: Added value of HER-2 amplification testing by multiplex ligation-dependent probe amplification (MLPA)
Authors: H-J van Slooten, CC Kuijpers, CB Moelans, A Horstman, S Al-Janabi, JW Hinrichs, PJ van Diest, M Jiwa
Journal: Cancer Research (2012)

Abstract Introduction Accurate determination of HER-2 status is critical for selection of breast cancer (BC) patients for trastuzumab treatment. According to the most commonly used testing protocol, patients with 3+ immunohistochemistry (IHC) are considered for trastuzumab. In addition, 2+ IHC cases are tested for gene amplification and, when amplified, these patients are considered for trastuzumab treatment as well. Because in our experience IHC results have been proven to be sensitive to pre-analytical variation and inter- and intra-observer variation, we apply amplification testing not solely to 2+, but also to 1+ and 3+ cases. At Symbiant Pathology Expert Centre, a validation study (n = 99) comparing MLPA with chromogenic in situ hybridization (CISH) showed 100% concordance. Starting from April 2011, MLPA has been used as the method for HER-2 amplification testing, because in our hands this technique is more time- and cost-effective than CISH for analyzing large sample numbers. CISH was performed when MLPA was inconclusive, IHC score was heterogeneous or when invasive carcinoma could not be physically separated from DCIS. Here we report the results of a comparison between HER-2 amplification tests and IHC in a cohort of 928 BC patients. Methods Pathology reports of 928 BC patients from 4 pathology laboratories were retrospectively reviewed. 728 patients were diagnosed between April 2011 and February 2012 in one of three laboratories of Symbiant Pathology Expert Centre. The other 200 patients were diagnosed in University Medical Centre Utrecht between January 2010 and December 2011. 18 patients had multiple tumors that were included as separate cases. In total, 949 tumors were reviewed. Results With IHC, major differences are observed between the 4 pathology laboratories concerning the percentage of cases scored as 0–1+ and 2+ (Table 1). A considerable number of 3+ cases (6.4%) failed to show gene amplification by MLPA and/or CISH. A smaller percentage of 0–1+ cases (1.8%) did show gene amplification (Table 2). 90 equivocal cases were double tested by CISH and MLPA. In 52/90 of these cases (58%) at least one test was inconclusive. The other 38 (42%) cases showed 100% concordance between MLPA and CISH. Conclusion MLPA is an accurate and cost-effective method for the determination of HER-2 status. We recommend the use of a gene amplification test to confirm HER-2 status in all IHC scores, not just the 2+ cases. However, it is still unclear whether the small subgroups of patients showing only HER-2 protein overexpression or only HER-2 gene amplification would benefit from trastuzumab. Follow-up data are therefore needed to determine the clinical value of HER-2 status assessed by each technique in order to improve the current standard of care for HER-2 testing. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-03.
Abstract 721: Multiplexed systems pathology for in-depth analysis of the tumor microenvironment: a strong correlation between pAkt and androgen receptor in the epithelial component of prostate cancer.
Authors: Sami Blom, Petra Mäki-Teeri, Tuomas Mirtti, Antti Rannikko, Jenni Säilä, Teijo Pellinen, Olli Kallioniemi
Journal: Cancer Research (2013)

Abstract It is important to understand the heterogeneity across the cancer tissue as well as the spatial interactions and signaling between the different components that constitute the tumor microenvironment; epithelium, stroma, inflammatory cells, etc. The state of the tumor microenvironment and its variability within and in between tumors may give important insights on cancer initiation and progression, diagnostics, prognostics and therapeutic assessment. Thus, there is a major need to assess multiple molecular targets simultaneously, quantitatively, and within the specific tumor sub-compartments. Here, we demonstrate a systems pathology approach for quantitative detection of multiple proteins in formalin-fixed paraffin-embedded patient tissue samples using a combination of immunohistochemistry and high-throughput fluorescence imaging. The study cohort consisted of 50 prostate cancer tissue samples from 25 patients exhibiting different disease stages in a tissue microarray (TMA) format. We developed a multiplexed assay for detecting pAkt, AR, and cytokeratin 8 (CK8) simultaneously using fluorescent nanoparticle labeling and high-throughput quantitative imaging. Fluorescent signals of pAkt and AR were automatically quantified within the segmented CK8-positive prostate epithelium. The stromal compartment and the non-malignant prostate tissue were analysed separately. Our results showed that the expression of pAkt and AR correlated strongly in the prostate cancer epithelium (Pearson correlation coefficient 0.89, p &amp;lt; 0.001). This suggests that the androgen-dependent signaling is strongly associated with the pAkt signaling in cancer, with potential ramifications for administrating and monitoring anti-androgens and/or Akt-inhibitor therapy. The systems pathology approach enables quantitative in situ multianalyte detection for any key cancer signaling proteins. The analyses can be readily expanded to TMAs of large prospective or clinical trial cohorts with automated imaging. The ability to quantitatively study the spatial arrangement of the tumor microenvironment could have decisive advantages and improve the diagnostic and therapeutic predictions. Citation Format: Sami Blom, Petra Mäki-Teeri, Tuomas Mirtti, Antti Rannikko, Jenni Säilä, Teijo Pellinen, Olli Kallioniemi. Multiplexed systems pathology for in-depth analysis of the tumor microenvironment: a strong correlation between pAkt and androgen receptor in the epithelial component of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 721. doi:10.1158/1538-7445.AM2013-721
Psychoanalysis helps doctors understand patients
Authors: N. Byrne, R. Harland
Journal: BMJ (2012)

Sometimes it’s embarrassing to be a psychiatrist. Psychiatry has always strived like a younger sibling to establish its status as equivalent to physical medicine, borrowing its clothes to do so. But they don’t fit. The strident tone of non-psychiatrists Salkovskis and Wolpert’s argument against psychoanalysis also belies this anxiety.1 However, anything but the most primitive …