tbuckley/cabot-search huggingface dataset:
Measuring the public health impact of the aneuploidies.
Authors: H B Newcombe
Journal: Environmental Health Perspectives (1979)

If the protection of man against mutagenic agents in general, and against those that cause aneuploidies in particular, is to have an increasingly rational basis with the passage of time, quantitative or at least semiquantitative assessments of risks are needed. These should take into account both the likely numbers of induced cases and the likely severities of the different conditions. In the past, quantitative data relating to severity have been limited or nonexistent, but the data sources exist by which follow-up studies may be carried out to determine age-specific and cumulative risks of hospitalization and death, the durations of hospital stays, and the economic burden to society which these represent. To illustrate the use of such sources, the cumulative risks of death in children with anomalies of the autosomes and of the sex chromosomes, over the first 19 years of life, are compared with those for other kinds of hereditary and environmentally caused handicaps that are reported in that age group.
P1267 CLINICAL PRESENTATION OF CYSTIC FIBROSIS-ASSOCIATED LIVER DISEASE AFTER LUNG TRANSPLANTATION
Authors: K. Staufer, E. Halilbasic, S. Schick, S. Harm, A. Brichta, A. Ba-Ssalamah, P. Jaksch, W. Klepetko, M. Trauner, L. Kazemi-Shirazi
Journal: Journal of Hepatology (2014)
Abstract 5626: EBP50: Novel biomarker for resistance to endocrine and HER-2 targeted therapies in breast cancer. .
Authors: Guowei Gu, Arnoldo Corona-Rodriguez, Kyle Covington, Natalie Fernandez, Jianling Zhou, Weiyan Cai, Sebastiano Ando’, Suzanne A.W. Fuqua
Journal: Cancer Research (2013)

Abstract Backgroud: Na+/H+ Exchanger Regulatory Factor (NHERF1) also named ERM Binding Protein 50 (EBP50) functions as a molecular scaffold to coordinate ion transport and second messenger signal transduciton. Recently, a number of studies suggest a role for EBP50 expression in cancer progression. Methods: Microarray profiling. Stable transfection. Soft agar and MTT growth assays. Immunoblot and immunoprecipitation assays. Confocal microscopy. Duolink in situ. Results: The mean levels of EBP50 were reduced in tamoxifen (Tam)-resistant, metastatic breast tumors compared to Tam-sensitive tumors. Knockdown of EBP50 decreased Tam sensitivity in MCF-7 and ZR-75B cells. EBP50 knockdown cells showed higher levels of phosphorylated HER2 and EGFR, as well as their downstream signalling pathways. PI3K/AKT inhibitors were able to restore Tam sensitivity in knockdown cells. Similarly, knockdown EBP50 in ERα/HER2 positive BT-474 cells increased constitutive pHER2 and these cells were resistant not only to Tam, but also to Trastuzumab (Tras) treatment. An EGFR inhibitor or Lapatinib were able to restore Tras sensitivity. Overexpression of EBP50 restored Tam sensitivity in BT-474 cells. We demonstrate that EBP50 is capable of binding to HER2 and ERα using immunoprecipitation and PLA assay, suggesting that EBP50 interacts directly with both. Overexpression of EBP50 decreased pHER2 and pEGFR levels suggesting that EBP50 can downregulate its activity. EBP50 overexpression upregulated ERα transcriptional activity. ERα transcriptional activity in cells overexpressing EBP50 was costitutively higher and more sensitive to Tam. We previously published that Dicer overexpression and loss of RhoGDIα were associated with Tam resistance. Interestingly, EBP50 knockdown was associated with higher Dicer and lower RhoGDIα levels suggesting that Tam resistance is associated with inter-related mechanisms. We performed microarray analysis and identified kinase signiture in EBP50 knockdown cells. This kinase signature predicts Tam resistance. Our data suggest that EBP50 is a novel negative regulator of HER2 signaling, and its loss confers resistance to both Tam and Tras. We hypothesize that EBP50 levels might be a new predictive biomarker for targeted therapy. Citation Format: Guowei Gu, Arnoldo Corona-Rodriguez, Kyle Covington, Natalie Fernandez, Jianling Zhou, Weiyan Cai, Sebastiano Ando’, Suzanne A.W. Fuqua. EBP50: Novel biomarker for resistance to endocrine and HER-2 targeted therapies in breast 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 5626. doi:10.1158/1538-7445.AM2013-5626
Abstract P2-03-01: An Investigation of Factors Influencing Real-Time Tissue Elastography Score
Authors: Y Nishiyama, U Sakaguchi, K Matsushita
Journal: Cancer Research (2010)

Abstract [Purpose] At 32nd SABCS, we reported that Real-time Tissue Elastography (EG) score was useful in the examinations of mass-forming breast lesions. The results suggested that a possibility of being invasive carcinoma may practically be ruled out when a mass-forming breast lesion scored 1 or 2 on EG. Because the stiffness is relatively visualized in EG, it is possible that the score is influenced by the state of the patient's breast. We examined the factors influencing EG scores in mass-forming breast lesions. [Subject and Method] EG scores of 502 patients with breast lesions (150 malignant, 352 benign) whose tissues were diagnosed histopathologically from October 2007 to December 2009 were studied. The hardness was scored on a scale 1 to 5 on Tsukuba elasticity scoring system. [Results] In the 502 cases of mass-forming breast lesions there was a significantly higher score for non-invasive carcinoma and invasive carcinoma than for benign lesions (&amp;lt; 0.0001). No difference in score was observed in a comparison of the location (lateral quadrants, medial quadrants) of the mass-forming lesion. There were significantly lower scores (&amp;lt; 0.0001) in 10 mm in diameter or smaller when comparing three groups of tumor mass diameters: 10 mm in diameter or smaller, 11-20 mm, and 21-30 mm. When the breast density of two groups were examined, “almost entirely fat or scattered fibroglandular tissue” group and “heterogeneously dense or extremely dense” group, there were significantly low scores in the “heterogeneously dense or extremely dense” group (&amp;lt; 0.0001). When the two groups divided by median area of the mammography were examined, there were significantly low scores in the larger breast group (&amp;lt; 0.0001). Although in the total cases examined, all cases were benign in score 1, 6% were malignant in score 2 (5 cases non-invasive carcinoma, 4 cases invasive carcinoma). When 3 cases in which pathology results of the surgical specimen were obtained were examined among the 4 cases of invasive carcinoma, widespread intraductal spread was observed in the surrounding invasive carcinoma. [Conclusion] Through this investigation we ascertained that EG scores are influenced by lesion size and the state of the patient's breast. In addition, care must be taken given the possibility of low scores in invasive carcinoma with widespread intraductal spread. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-03-01.
Granulocyte–macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial)
Authors: X Thomas, P Fenaux, H Dombret, S Delair, F Dreyfus, H Tilly, A Vekhoff, P Cony-Makhoul, V Leblond, X Troussard, C Cordonnier, T de Revel, M Simon, F Nicolini, AM Stoppa, M Janvier, D Bordessoule, P Rousselot, M Ffrench, JP Marie, E Archimbaud
Journal: Leukemia (1999)
Abstract 4486: Mitochondrial DNA copy number is associated with colorectal cancer risk
Authors: Bharat Thyagarajan, Renwei Wang, Helene Barcelo, Woon-Puay Koh, Jian-Min Yuan
Journal: Cancer Research (2012)

Abstract Background: Mitochondrial DNA (mtDNA) copy number variation is common in colorectal tumors and one case control study showed mtDNA copy number to be associated with increased colorectal cancer risk. Data on mtDNA copy number and colorectal cancer risk in prospective cohorts is lacking. Objectives: We evaluated the association between mtDNA copy number in peripheral blood and colorectal cancer risk among participants of the Singapore Chinese Health Study. Methods: We conducted a nested case-cohort study of 422 colorectal cancer cases (168 incident cases with pre-diagnostic blood and 254 prevalent cases with post-diagnostic blood) and 880 controls who were free of colorectal cancer at blood draw. The relative mtDNA copy number was measured using real time PCR. Analysis of covariance and logistic regression methods were employed to examine the association between mtDNA copy number and colorectal cancer risk. Results: mtDNA copy number was significantly higher among colorectal cancer cases than controls (geometric mean: 0.62 vs. 0.50, p&amp;lt;0.0001). There was a U shaped relationship between the mtDNA copy number and colorectal cancer risk. Individuals in the low and high mtDNA copy numbers were at increased risk of colorectal cancer; odds ratios (95% confidence interval) for developing colorectal cancer for the lowest and highest quartile of mtDNA copy numbers were 1.83 (1.16-2.90) and 3.54 (2.25-5.55), respectively, compared to those in the second quartile of mtDNA after adjustment for potential confounders (p for curvilinear trend &amp;lt;0.001). The lowest mtDNA copy number quartile was associated with colorectal cancer only in the pre-diagnostic blood samples (OR=3.22, 95% CI:1.51-6.85) but not in the post-diagnostic blood samples (OR=1.36, 95% CI:0.80-2.32), implying that cancer status impacts the mtDNA copy number-colorectal cancer risk association. Conclusions: This is the first study to show a prospective association between mtDNA copy number and colorectal cancer risk. Further studies are needed to confirm this association and understand the biological significance of these observations. 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 4486. doi:1538-7445.AM2012-4486
Bile duct obstruction after transjugular intrahepatic portosystemic shunt implantation
Authors: T. Karlas, A. Hoffmeister, J. Fuchs, M. Tröltzsch, V. Keim
Journal: Endoscopy (2013)

Transjugular intrahepatic portosystemic shunt (TIPS) implantation is a standard treatment option for patients with liver cirrhosis and the complications of portal hypertension [1]. The safety and efficacy of the procedure have been studied extensively [2]. Biliary complications are rare and comprise biliary fistula and bilioma [3] [4].
ECHOCARDIOGRAM INTERPRETATION VIA GOOGLE GLASS
Authors: Jedrek Wosik, Thao Duong, Jose R. Martinez Parachini, Erica Resendes, Bavana Rangan, Michele Roesle, Nicole Minniefield, Laura Collins, Jerrold Grodin, Shuaib Abdullah, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)
Taking Care of the Hateful Patient
Authors: James E. Groves
Journal: New England Journal of Medicine (1978)

"Hateful patients" are not those with whom the physician has an occasional personality clash. As defined here they are those whom most physicians dread. The insatiable dependence of "hateful patients" leads to behaviors that group them into four stereotypes: dependent clingers, entitled demanders, manipulative help-rejecters and self-destructive deniers. The physician' negative reactions constitute important clinical data that should facilitate better understanding and more appropriate psychological management for each. Clingers evoke aversion; their care requires limits on expectations for an intense doctor-patient relationship. Demanders evoke a wish to counterattack; such patients need to have their feelings of total entitlement rechanneled into a partnership that acknowledges their entitlement--not to unrealistic demands but to good medical care. Help-rejecters evoke depression; "sharing" their pessimism diminishes their notion that losing the symptom implies losing the doctor. Self-destructive deniers evoke feeling of malice; their management requires the physician to lower Faustian expectations of delivering perfect care.
Abstract 4431: Antitumor activity of nanosponge-encapsulated camptotechin in human prostate tumors
Authors: Rosalba Minelli, Roberta Cavalli, Roberto Fantozzi, Chiara Dianzani, Piergiorgio Pettazzoni, Leigh Ellis, Li Shen, Roberto Pili
Journal: Cancer Research (2011)

Abstract Drug delivery technologies are new and powerful approaches to enhance the pharmacological properties of drugs by improving their availability and stability and by reducing their side effects. Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor that presents strong antitumoral efficacy in both hematological and epithelial malignancies. However, its use is limited because of its high degradability and weak solubility. Indeed, the structure of camptothecin presents a lactone ring that is subjected to hydrolysis in physiological conditions with consequent inactivation of the topoisomerase binding activity. In the present study a new formulation of CPT embedded in cyclodextrin-based nanosponges (CN-CPT) has been evaluated in vitro and in vivo on prostate cancer models. CN-CPT manifested a strong antitumoral efficacy revealed by MTT and colony forming assay on hormonal independent PC3 and DU145 cells, significantly higher as compared to the same dose of free CPT. Moreover, cell cycle analysis and annexin V/PI staining showed that CN-CPT treatments induced significant apoptotic cell death at 1 nM (61.7% apoptotic cell death; p&amp;lt;&amp;lt;0.001), where free CTP (4.36% apoptotic cell death) was not effective. The efficacy of CN-CPT has been tested in vivo in PC3 and DU145 xenograft experiments that have confirmed a significant improvement of antitumoral activity of CN-CPT as compared to CPT. To evaluate possible antimetastatic activity of CPT, in vitro experiments of tumor cell adhesion to HUVECs as a model of endothelium and cell motility were performed. Results showed that CN-CPT is effective at lower doses compared to CPT in inducing inhibition of adhesion and motility. In order to evaluate whether androgen receptor signaling could affect the responsiveness to either CPT or CN-CPT the AR expressing murine models of prostate cancer (MYC-AD, PTEN8 and PTEN CAP8) have been used. Results showed that expression of functional AR diminished the efficacy of both C PT and CN-CPT. However the latter still exerted greater effects compared to CN-CPT. Taken together these results support the use of CPT and the development of nanotechnologies for drug delivery in the treatment of castrate refractory prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4431. doi:10.1158/1538-7445.AM2011-4431
Abstract 3449: Development of small molecule Bcl-XL inhibitors for treatment of lung cancer.
Authors: Dongkyoo Park, Andrew T. Magis, Rui Li, Taofeek K. K. Owonikoko, Gabriel L. Sica, Shi-Yong Sun, Suresh S. Ramalingam, Fadlo R. Khuri, Walter J. Curran, Xingming Deng
Journal: Cancer Research (2013)

Abstract Bcl-XL is a major anti-apoptotic protein in the Bcl-2 family whose overexpression is more widely observed in human lung cancer cells than that of Bcl-2, suggesting that Bcl-XL is more biologically relevant and therefore a better therapeutic target for lung cancer. Here, we screened small molecules that selectively target the BH3 domain (aa 90-98) binding pocket of Bcl-XL using the UCSF DOCK 6.1 program suite and the NCI chemical library database. We identified two new Bcl-XL inhibitors (BXI-61 and BXI-72) that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells. Fluorescence polarization assay reveals that BXI-61 and BXI-72 preferentially bind to Bcl-XL protein but not Bcl2 in vitro with high binding affinities. Treatment of cells with BXI-72 results in disruption of Bcl-XL/Bak interaction, oligomerization of Bak and cytochrome c release from mitochondria. These two BXI compounds potently repress lung cancer xenografts in vivo without significant normal tissue toxicity within effective doses. Importantly, BXI-72 can also overcome acquired radioresistance of lung cancer. Based on our findings, the development of BXI(s) as a new class of anticancer agents is warranted and represents a novel strategy for improving lung cancer outcome. Citation Format: Dongkyoo Park, Andrew T. Magis, Rui Li, Taofeek K. K. Owonikoko, Gabriel L. Sica, Shi-Yong Sun, Suresh S. Ramalingam, Fadlo R. Khuri, Walter J. Curran, Xingming Deng. Development of small molecule Bcl-XL inhibitors for treatment of lung 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 3449. doi:10.1158/1538-7445.AM2013-3449
Transient Angiolymphoid Hyperplasia and Kaposi's Sarcoma after Primary Infection with Human Herpesvirus 8 in a Patient with Human Immunodeficiency Virus Infection
Authors: Eric Oksenhendler, Dominique Cazals-Hatem, Thomas F. Schulz, Véronique Barateau, Laurence Grollet, Julie Sheldon, Jean-Pierre Clauvel, François Sigaux, Félix Agbalika
Journal: New England Journal of Medicine (1998)

2][3] HHV-8 has also been detected in primary effusion lymphomas, 4 Castleman's disease, 5 and multiple myeloma 6 and reported anecdotally in cases of angioimmunoblastic lymphadenopathy and germinal-center hyperplasia. 7Indirect immunofluorescence and immunoblot assays, based on antigens from a latently infected lymphoma cell line, have shown that HHV-8 is not a ubiquitous viral infection in humans.][10][11][12][13] Seroconversion has been documented in stored serum samples from homosexual men enrolled in a large cohort study and was associated with a high risk of Kaposi's sarcoma within two years after seroconversion. 14It is controversial whether primary infection with HHV-8 produces an acute clinical syndrome.We describe a patient infected with human immunodeficiency virus (HIV) who had a sudden onset of fever, arthralgia, cervical lymphadenopathy, and splenomegaly that spontaneously resolved within eight weeks.Pathological examination of the cervical nodes identified angiolymphoid hyperplasia and foci of Kaposi's sarcoma.Retrospec-
Treatment of Cryptococcal Meningitis Associated with the Acquired Immunodeficiency Syndrome
Authors: Charles M. van der Horst, Michael S. Saag, Gretchen A. Cloud, Richard J. Hamill, J. Richard Graybill, Jack D. Sobel, Philip C. Johnson, Carmelita U. Tuazon, Thomas Kerkering, Bruce L. Moskovitz, William G. Powderly, William E. Dismukes
Journal: New England Journal of Medicine (1997)

Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization.
BMA launches judicial review against contract imposition
Authors: Abi Rimmer
Journal: BMJ (2016)

The BMA has launched a judicial review challenging the lawfulness of the health secretary’s decision to impose a new contract on junior doctors in England.

The move came after NHS Employers published the new contract, which sets out terms and conditions for junior doctors.1 At the same time, the Department of Health published an equality analysis of the contract.2

After a breakdown of negotiations …
AB0371 State of the art for treating-to-target in sle: a systematic literature review
Authors: G. Bertsias, M. Mosca, A. Levitsky, R. F. Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In order to develop "treat-to-target" recommendations for SLE, a panel of experts identified topics related to the treatment of the disease and commissioned a systematic literature search. <h3>Objectives</h3> To provide the literature-based evidence for treat-to-target recommendations in SLE. <h3>Methods</h3> Twelve topics were identified and a systematic PubMed search was performed using an array of keywords (<b>Table 1</b>). Out of 9278 articles identified initially, 440 were selected for further review. Evidence was categorized based on sample size, study design, and estimated effect sizes. <h3>Results</h3> SLE disease activity (both global and organ-specific) is associated with accrual of organ damage and mortality, and shows modest inverse association with quality of life (QoL). In lupus nephritis, achieving complete renal response is associated with good prognosis. Only a fraction (10-40%) of patients can achieve long-lasting disease remission, and major SLE flares, particularly renal disease flares, are associated with adverse outcomes. Organ damage accrual is a poor prognostic factor and shows modest association with QoL. The long-term benefits and risks of treating asymptomatic but serologically active patients have not been established. In active renal or inflammatory neurological disease, the combination of immunosuppressives with glucocorticoids is superior to glucocorticoids alone as induction treatment. In lupus nephritis, long-term maintenance immunosuppressive treatment may prevent renal flares and improve outcome. In chronic SLE treatment, higher cumulative doses of glucocorticoids are associated with damage accrual. In antiphospholipid syndrome, there is limited evidence for superiority of variable intensity anticoagulation regimens. Non-randomized evidence suggests that use of antimalarials is associated with reduced damage accrual. Adjunctive therapies are safe in lupus although there is no evidence for association with improved long-term outcomes. <h3>Conclusions</h3> A systematic literature review yielded a large set of data to be considered by the treat-to-target working party for further development. <h3>Disclosure of Interest</h3> G. Bertsias: None Declared, M. Mosca: None Declared, A. Levitsky: None Declared, R. Van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB