tbuckley/cabot-search huggingface dataset:
Cigarette Smoking as a Risk Factor for Epidemic A(H1N1) Influenza in Young Men
Authors: Jeremy D. Kark, Moshe Lebiush, Lotte Rannon
Journal: New England Journal of Medicine (1982)

We studied an outbreak of A(H1N1) influenza in an Israeli military unit of 336 healthy young men to determine the relation of cigarette smoking to the incidence of clinically apparent influenza and to the influenza-antibody response. Of 168 smokers, 68.5 per cent had influenza, as compared with 47.2 per cent of nonsmokers (P less than 0.0001). Influenza was also more severe in the smokers; 50.6 per cent of the smokers lost work days or required bed rest, or both, as compared with 30.1 per cent of the nonsmokers. The proportion of all influenza in smokers that was attributable to smoking was 31.2 per cent (95 per cent confidence intervals, 16.5 to 43.1 per cent). For severe influenza, the attributable risk in the smokers was 40.6 per cent (95 per cent confidence intervals, 21.6 to 54.8 per cent). A quarter of all severe morbidity from influenza in the overall study population was attributable to smoking. Antibody levels to A/USSR/90/77(H1N1) antigen were higher in smokers but not markedly so. We conclude that smoking is a major determinant of morbidity in epidemic influenza and may contribute substantially to incapacitation in outbreaks in populations that smoke heavily.
FRI0260 Survival, causes of death and mortality risk factors in systemic sclerosis:
Authors: J.G. Ovalles-Bonilla, J. Martínez-Barrio, F. Lόpez-Longo, I. de la Torre, C. González, L. Valor, M. Montoro-Άlvarez, F. Aramburu, C. Marín, L. Martínez-Estupiñán, J. Nieto, M. Hinojosa, N. Bello, I. Monteagudo, L. Carreño
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Among the rheumatic diseases, Systemic Sclerosis (SSc) stands out as a severely incapacitating and life-threatening disease. <h3>Objectives</h3> To analize the causes of death, survival and risk factors for mortality in SSc patients. <h3>Methods</h3> Demographic, clinical, immunological and mortality data were obtained from a long term prospective cohort of SSc patients recruited between 1986 and 2011 in the Rheumatology Department of Gregorio Marañon Hospital in Madrid, Spain. Patients were divided into 4 groups: limited SSc, diffuse SSc, SSc in overlap and SSc in mixed connective tissue disease (SSc-MCTD). ANOVA, Kruskal-Wallis or χ<sup>2</sup> tests were used to identify differences among groups; Kaplan-Meier and Mantel-Haenszel (log-rank) analysis were used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. <h3>Results</h3> A total of 137 patients were included, of whom 122 (89%) were women. Mean age at diagnosis was 43±17.7 years, and the mean follow-up time was 15.2 years. A global mortality of 34 (24.8%) cases was observed: 8 related to cardiac involvement, 8 to serious infections, 7 to pulmonary involvement, 6 to neoplasms, 2 to renal involvement and 3 to other causes. Survival rates from disease onset were 96, 90, 75 and 50% at 5, 10, 20 and 30 years, respectively. Limited SSc and SSc-MCTD show a significantly (p=0.002) higher survival mean time (33.7 years) when compared to diffuse and overlap variants (22.4 years). Poorer survival is associated with interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies (see table 1). Independent prognostic factors for mortality were interstitial lung disease (HR 6.8, CI 95% 1.5-30, p=0.012), pulmonary arterial hypertension (HR 5.6, CI 95% 1.2-26.9, p=0.032), and Anti-Ro antibodies (HR 3.9, CI 95% 1.5-9.8, p=0.004). <h3>Conclusions</h3> A 20-year survival was seen in more than 70% of SSc patients. The main causes of death are cardiac involvement, severe infections and pulmonary manifestations. Diffuse SSc, SSc-MCTD, interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies are the main risk factors for mortality. <h3>Disclosure of Interest</h3> None Declared
Abstract P2-10-35: The grade of accompanying DCIS in IDC as important prognostic factor
Authors: JY Kim, H-G Moon, WS Han, DY Noh
Journal: Cancer Research (2012)

Abstract Backgrounds: The issue of whether concomitant ductal carcinoma in situ (DCIS) affects the prognosis of with invasive breast cancer is important but studies of this have reported inconsistent results. So we aimed to assess the character and prognostic difference in infiltrating ductal carcinoma (IDC) according to accompanying DCIS status. Methods: We reviewed the medical records of the patients who underwent surgery for IDC. Male patients, patients who had received neoadjuvant chemotherapy, patients with synchronous bilateral breast cancer, follow-up periods &amp;lt;6months or those with other malignancies were excluded from the study. In cases in which a DCIS component was present in IDC, the degree of differentiation and the presence of necrosis were assessed to subdivide DCIS into two groups; low and high grade. Results: A total of 1751 patients were included, and 1384 patients (79.0%) had concomitant DCIS; 337 had low-grade DCIS, and 1047 patients had high-grade DCIS. The low-grade DCIS group had a significantly lower TNM stage than the high-grade DCIS group. The majority of cases with low-grade DCIS, were ER-positive (85.2%), PR-positive (81.3%) and had low Her-2 (98.7%). When we analyzed the survival rates according to the presence of DCIS, no statistical significance was founded. However, a subgroup analysis showed that the patients with low-grade DCIS survived significantly longer than other patients, whereas those with high-grade DCIS had poorer survival (5 year event-free survival rate; low-grade DCIS vs. without DCIS vs. high-grade DCIS, 97% vs. 93% vs. 86%, p = 0.001). Specially, in patients with lymph node involvement, accompanying high-grade DCIS was independent predictor distant metastasis (HR 5.0, p = 0.026, 95% CI 1.21–20.92). Conclusion: The important factor that affect prognosis of IDC with DCIS is not the presence itself of DCIS component but the grade of DCIS. The patients with low-grade DCIS had a good prognosis and those with high-grade DCIS had a poor prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-35.
Enterovirus Déjà Vu
Authors: John F. Modlin
Journal: New England Journal of Medicine (2007)

More than 90 human enterovirus serotypes have now been identified in three distinct waves of discovery. The three poliovirus serotypes were first isolated from nonhuman primates in the course of painstaking experiments performed during the first half of the 20th century. The use of small laboratory animals and the advent of cell culture in midcentury led to the description of 61 more enteroviruses that we know as coxsackieviruses, echoviruses, and the "newer" enteroviruses. The application of polymerase chain reaction and genomic sequencing has recently permitted characterization of approximately 30 previously unidentified enterovirus serotypes and undoubtedly will uncover more.Enterovirus 71 . . .
MB-18 * POST-TRANSLATIONAL REGULATION OF ATOH1: FROM CEREBELLAR DEVELOPMENT TO MEDULLOBLASTOMA FORMATION
Authors: S. M. Cigna, A. Forget, L. Bihannic, M. Remke, S. Humbert, M. D. Taylor, A. Lasorella, O. Ayrault
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant pediatric tumor of the central nervous system. Human MBs have been classified by gene expression profiling into four subgroups. A subgroup of human MBs (∼25%) harbors constitutive activation of the Sonic Hedgehog (SHH) signaling pathway. Atoh1, a proneural basic helix-loop-helix transcription factor is essential for cerebellum development and collaborates with SHH signaling for the formation of SHH MB in vivo. Because Atoh1 acts as a lineage dependency transcription factor in SHH MB, mechanisms controlling Atoh1 expression are keen interest in the field. However, how this master transcription factor is regulated has remained poorly understood. Using a proteomic approach we recently described a functional interaction between Atoh1 and the E3 ubiquitin ligase Huwe1 during cerebellar development. We uncovered that SHH regulates Atoh1 degradation in a phospho- and E3-dependent manner in cerebellar granule neuron progenitors. In human SHH MB, low HUWE1 expression is associated with poor prognosis. These results led us to deepen the relationship between Huwe1 and Atoh1 in SHH MB formation. More specifically, we wish to explore whether Huwe1 could cooperate with the constitutive activation of the SHH pathway for the formation of SHH MB in vivo.
AB0652 Thrombin Activated Fibrinolysis Inhibitors (TAFI) Levels in Active Diffuse Systemic Sclerosis Patients
Authors: Z. Ozbalkan, S. Apras, S.M. Pehlevan, K. Sahin, K. Yasar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Thrombin-activated fibrinolysis inhibitors (TAFI) is activated by the endothelial surface thrombin and has an important role on the relation of coagulation, fibrinolysis and inflammatory systems. Basically, activation of TAFI down-regulates fibrinolysis and also, leads the neutrophil activation triggered by C5 and kinin related inflammatory systems. <h3>Objectives</h3> We aimed to show the relation between the serum TAFI levels and disease activity of diffuse systemic sclerosis patients (SSc). <h3>Methods</h3> 13 active SSc female patients with interstitial lung disease and 10 healthy women were involved in to the study. From the serum samples of both groups, TAFI levels were measured by ELISA method using pefakit TAFI (Penthafarm, Basel). <h3>Results</h3> Serum TAFI levels of SSc patients was 63.1±19.1 mg/dL SD (min-max: 30-90 mg/dL) and control group9s TAFI level was 41.0±11.1mg/dL SD (min-max: 9-59 mg/dL). All data was analysed by Mann-Whitney U test. P&lt;0.05 was accepted as significant. Comparison between the scleroderma and control groups TAFI levels revealed that TAFI levels in patient group was significantly higher (p=0.009). <h3>Conclusions</h3> Fibrinolytic activity is linked to inflammation. Increased amount of TAFI in serum may explain why fibrin formation is so prominent in SSc. And also TAFI may play important roles in the mechanism of intraalveolar hypofibrinolysis associated with interstitial lung disease. <h3>References</h3> MJ Peters. Ann Rheum Dis 2009; 68(7):1232-3. Ringwald J. Throm Res 2002; 119(1):129-31. Sak S. J Throm Haemost 2003; Dec;1(12): 2510-5. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4853
Interleukin 1 (IL-1)-Dependent Melanoma Hepatic Metastasis In Vivo; Increased Endothelial Adherence by IL-1-Induced Mannose Receptors and Growth Factor Production In Vitro
Authors: F. Vidal-Vanaclocha, A. Alvarez, A. Asumendi, B. Urcelay, P. Tonino, C. A. Dinarello
Journal: JNCI Journal of the National Cancer Institute (1996)

The growth of cancer cells in inflammatory tissue is often observed. This can be the result of favorable conditions for endothelial cell adherence and/or increased production of local growth factors. The role of the proinflammatory cytokine interleukin 1 (IL-1) in the prometastatic and growth-promoting environment of inflammation was studied in vivo, and the mechanism of cytokine action was studied in vitro as well. Systemic inflammation was induced by the intravenous injection of IL-1β or lipopolysaccharide (LPS), and the hepatic metastasizing ability of B16 melanoma (B16) cells following intrasplenic injection was studied. IL-1 receptor blockade was accomplished with the use of the IL-1 receptor antagonist (IL-1Ra). In vitro, IL-1Ra was used to assess the mechanism for prometastasis and growth promotion of cultured hepatic sinusoidal endothelium stimulated with LPS. There was a statistically significant ( P <.01) enhancement in the parameters of hepatic metastasis when B16 cells were injected intrasplenically either 4 hours after IL-1 injection or 6 or 12 hours after LPS injection. IL-IRa pretreatment reduced IL-1-induced enhancement of metastasis by 73%-87% and completely inhibited the augmentation of metastasis following LPS injection. In vitro, the adherence of melanoma cells to LPS-treated endothelium increased nearly twofold but was completely abrogated when IL-1Ra was added before LPS. Similar to melanoma adherence, a 2.5-fold increase ( P <.05) in functional mannose receptors was observed with LPS treatment but was prevented by the addition of IL-1Ra. IL-1Ra did not affect basal mannose-receptor activity in unstimulated epithelium. Mannose-receptor activity and B16 cell adherence significantly correlated ( r = .9) with LPS treatment. Conditioned medium from LPS-stimulated epithelium augmented B16 cell proliferation compared with control conditioned medium ( P <.01). Production of B16 cell growth factor(s) was markedly reduced ( P <.01) when IL-1Ra was added. These results demonstrate that systemic inflammation induces an enhancement of melanoma cell metastasis and growth by IL-1-dependent mechanisms in vivo. In vitro, the mechanism(s) is consistent with IL-1-mediated increase in expression of mannose receptors and production of tumor cell growth factor(s) from the endothelium. Given the multiple and complex cytokine cascade induced in vivo and in vitro during LPS-induced systemic inflammation, IL-1 plays a strategic role. Since IL-1Ra is without side effects in humans, studies on intraoperative infusion of IL-1Ra during tumor resection may be indicated. [J Natl Cancer Inst 1996;88:198–205]
Abstract 4838: Alpha-methyltryptophan, a blocker of the amino acid transporter SLC6A14, induces autophagy and apoptosis in SLC6A14-positive breast cancer and colon cancer cell lines
Authors: Senthil Karunakaran, Patricia V. Schoenlein, Muthusamy Thangaraju, Puttur D. Prasad, Vadivel Ganapathy
Journal: Cancer Research (2010)

Abstract SLC6A14 (also known as ATB0,+) is a Na+/Cl− -coupled amino acid transporter that transports 18 of the 20 proteinogenic amino acids, including all essential amino acids. Normal tissues express this transporter at low levels, whereas tumor tissues (colon, breast, and cervix) upregulate this transporter several-fold. The unique functional features of SLC6A14 (broad substrate specificity and multiple driving forces) make it an ideal transporter for tumor cells to maintain amino acid nutrition necessary for enhanced cell proliferation. We speculate that SLC6A14 could not only be an ideal tumor-specific delivery system for amino acid-based anti-cancer drugs but also be a direct drug target for cancer chemotherapy. Recently we identified alpha-methyltryptophan (ALT) as a blocker of SLC6A14. Here we examine the potential of this blocker as an anti-cancer agent in SLC6A14-positive breast and colon cancer cells. Treatment of MCF7 (a breast cancer cell line), HCT116 and LS174T (colon cancer cell lines) with ALT causes amino acid starvation as evidenced by the upregulation of asparagine synthetase and CHOP. These three cell lines are SLC6A14-positive. In contrast, ALT treatment of breast cancer cell line MDA-MB231, which is SLC6A14-negative, does not show any evidence of amino acid starvation. Similarly, ALT treatment has no effect on normal breast and colon epithelial cell lines (MCF10A and CCD841, respectively). These cell lines also do not express SLC6A14. These data show that ALT-induced amino acid starvation is mediated specifically through the blockade of SLC6A14. Since nutrient signaling is also associated with changes in mTOR pathway, we examined the influence of ALT treatment on phosphorylation of S6 and S6kinase. Blockade of SLC6A14 with ALT in SLC6A14-positive cancer cell lines leads to decreased mTOR signaling as evidenced by decreased phosphorylation of S6 and S6kinase. Again, such changes are not seen in SLC6A14-negative cancer or normal cell lines. The initial response of the SLC6A14-positive cancer cell lines to ALT treatment is induction of autophagy. ALT-induced autophagy is documented in these cells by light and electron microscopic examination as well as by biochemical means. Inhibition of autophagy with 3-methyladenine under these conditions leads to apoptosis. We conclude that SLC6A14 is a potential drug target for cancer chemotherapy and that ALT could serve as a lead compound for the future design of high-affinity blockers of SLC6A14. 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 4838.
Intestinal Absorption and Renal Extraction of Cystine and Cysteine in Cystinuria
Authors: Leon E. Rosenberg, Joseph L. Durant, James M. Holland
Journal: New England Journal of Medicine (1965)

A NUMBER of in vivo1 2 3 and in vitro4 5 6 studies in cystinuric patients have shown the presence of defects in renal and intestinal transport of the dibasic amino acids lysine, arginine and ornithine. However, studies of intestinal absorption of cystine and the mechanisms by which this amino acid appears in the urine in such marked excess in cystinuria have been far more difficult to interpret. An intestinal-transport defect for cystine has been demonstrated in vitro,5 , 6 and Milne and his co-workers3 have called attention to previous in vivo feeding studies suggesting defective absorption of this amino acid. Several studies7 8 9 have reported that . . .
AB0285 Which Score is Better to Assess Remission in Rheumatoid Arthritis?: Table 1.
Authors: K. Ben Abdelghani, S. Miladi, L. Souabni, A. Fazaa, S. Kassab, S. Chekili, A. Laatar, L. Zakraoui
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Various composite outcome measures have been developed in the last decade to evaluate Rheumatoid Arthritis (RA) activity, and the focus was in how to assess remission. The Ultrasonography (US) appears to be the best way to define remission but it is not always available. <h3>Objectives</h3> Our aim from this study was to investigate the accuracy of composite scores in classifying RA patients who were in remission using the absence of inflammatory activity detected by ultrasound (US) as a gold standard. <h3>Methods</h3> Sixty two patients followed up for RA were prospectively recruited. Among them, we identified patients in remission according to the Disease Activity Index 28 joints ≤2,6 (DAS28), the Simplified Disease Index ≤3,3 (SDAI), the Clinical Disease Index ≤2,8 (CDAI) and the American College of Rheumatology/European League Against Rheumatology (ACR/EULAR) 2011 criteria. B-mode and a Power Doppler (PD) US exam were assessed by a single rheumatologist who was experienced in US and blinded to the clinical and laboratory data. Twenty two joints were scanned (wrists, 10 metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints). Sensitivity, specificity and Positive Predictive value (PPV) for each score were calculated with as reference absence of Doppler signals in US. <h3>Results</h3> Among 62 patients screened, 30 (48%) were in remission according to the DAS28, 19 (31%) according to SDAI, 26 (42%) according to CDAI and 14 (23%) when new ACR/EULAR criteria were accomplished. Between all patients with active or not RA, nineteen had no Doppler signals in US. Considering "remission" to be the absence of joints with PD signal, the DAS28 was the most sensitive score while the ACR/EULAR criteria were the most specific. We resumed in table 1 our outcomes of sensitivity, specificity and PPV for each score of remission. <h3>Conclusions</h3> Ours results suggest that when considering remission as an absence of Doppler signal, the sensitivity of DAS28 was better than SDAI, CDAI and ACR/EULAR definitions of remission. While the ACR/EULAR criteria were the most specific. <h3>References</h3> Balsa A, De Miguel E and col. Superiority of SDAI over DAS-28 in assessing remission in rheumatoid arthritis patients using power Doppler ultrasonography as a gold standard. Rheumatology 2010. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2958
Abstract 998: Poly(ADP-Ribose) polymerase inhibitor overcomes Rad51- mediated prostate cancer cells’ resistance to Topoisomerase I inhibitor under hypoxia.
Authors: Minghui Wu, Jingsong Zhang, Xue Wang
Journal: Cancer Research (2013)

Abstract Intra-tumoral hypoxia has been proposed to create a “mutator” phenotype through down-regulation of DNA repair, leading to increased genomic instability and drug resistance. There is increasing interest to target hypoxic cancer cells with DNA-damaging agents and inhibitors of DNA repair. Here, we showed that hypoxia did not sensitize castration-resistant prostate cancer cells to the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib or the DNA-damaging topoisomerase I inhibitor: Irinotecan or SN38. Although DNA repair proteins like Rad51 were decreased under hypoxia, up-regulation of Rad51 and Rad51 nuclear foci formation was observed soon after treatment with veliparib and SN-38 under hypoxia. This Rad51 up-regulation occurred at the transcription level and was mediated at least in part by E2F1. Inhibiting Rad51 expression with siRNA overcame prostate cancer cells’ resistance to SN-38 under hypoxia. Combining veliparib with Irinotecan significantly enhanced DNA damage and apoptosis under both hypoxic and normoxic culture conditions. Such enhanced DNA damage and anti-tumor activities were seen in the presence of Rad51 up-regulation and confirmed in vivo with PC3 mouse xenografts. These data illustrate a dynamic regulation of Rad51 by prostate cancer cells in response to hypoxia and DNA damage. The veliparib and Irinotecan combination can be further explored as a treatment for metastatic castration-resistant prostate cancer patients who have progressed through standard treatments. Citation Format: Minghui Wu, Jingsong Zhang, Xue Wang. Poly(ADP-Ribose) polymerase inhibitor overcomes Rad51- mediated prostate cancer cells’ resistance to Topoisomerase I inhibitor under hypoxia. [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 998. doi:10.1158/1538-7445.AM2013-998