tbuckley/cabot-search huggingface dataset:
Iran deal and global health diplomacy
Authors: Mehdi Aloosh
Journal: The Lancet Global Health (2015)

In their Correspondence, Kamiar Alaei and colleagues (September, 2015)1Alaei K Alaei A Fox A Strengthening US–Iranian relations through public health.Lancet Glob Health. 2015; 3: e525-e526Summary Full Text Full Text PDF Scopus (5) Google Scholar suggest that the Iran–USA relationship could be normalised through academic educational and research collaborations, which has been defined as global health diplomacy. Diplomacy no longer only concerns power, security, and economics, but global challenges such as health. Foreign policies (eg, economic sanctions) can endanger health as well as promote it.2Kickbusch I Global health diplomacy: how foreign policy can influence health.BMJ. 2011; 342: d3154Crossref PubMed Scopus (50) Google Scholar The lifting of economic sanctions could stabilise, steadily driving up all prices including food to some extent, and address the limited availability of high quality drugs and medical devices.3Mohammadi D US-led economic sanctions strangle Iran's drug supply.Lancet. 2013; 381: 279Summary Full Text Full Text PDF PubMed Scopus (22) Google Scholar Sanctions have not only led to material shortages, but have also endangered mental health because of continuous threats. People exposed to stressful life events have higher mortality and morbidity.4Marmot M Wilkinson R Social determinants of health. Oxford University Press, Oxford2005Crossref Scopus (2389) Google Scholar Moreover, research including medical research in Iran has suffered greatly during the international economic sanctions. One of the bibliometric indicators of a country's scientific performance is the number of publications. According to Web of Science, the number of publications by Iranian authors in medical and health sciences has decreased from 23 409 in 2012 to 22 918 in 2013, whereas this number had been steadily increasing in the years before the economic and banking sanctions. In conclusion, the Iran nuclear deal is an opportunity to strengthen the academic and scientific relationship between Iran and the USA and to promote medical research activity and public health especially in Iran. Since Iranian citizens compose the sixth largest group of international practising physicians in the USA,5United States Physician Workforce IssuesFoundation for Advancement of International Medical Education and Research.http://www.faimer.org/research/workforce.htmlDate: 2010Google Scholar and in view of the academic positions that Iranian-Americans hold, their role in a scientific relationship could be prominent.6Aloosh M North America: US sanctions alarm physicians from Iran.Nature. 2015; 522: 419Crossref PubMed Scopus (6) Google Scholar I declare no competing interests.
Differential Association Between HDL Subclasses and the Development of Type 2 Diabetes in a Prospective Study of Japanese Americans
Authors: You-Cheol Hwang, Tomoshige Hayashi, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Marguerite J. McNeely, Edward J. Boyko
Journal: Diabetes Care (2015)

OBJECTIVE Recent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes. RESEARCH DESIGN AND METHODS The study enrolled 406 Japanese Americans (51% male) without diabetes, aged 34–75 years. Oral glucose tolerance tests were performed to determine type 2 diabetes status at baseline, 2.5 years, 5 years, and 10 years after enrollment. HDL2, HDL3, total HDL cholesterol, and visceral adipose tissue (VAT) area by computed tomography were measured at baseline. RESULTS In univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52–0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44–0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BMI, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area. CONCLUSIONS Subjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk.
Safety and efficacy of eculizumab in paroxysmal nocturnal hemoglobinuria evolving from patients with myelodysplastic syndrome and aplastic anemia
Authors: R. A. Brodsky, P. Hillmen, J. Schubert, L. Luzzatto, G. Socié, C. F. Mojcik, R. P. Rother, N. S. Young
Journal: Journal of Clinical Oncology (2007)

7033 Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) have been reported to be associated with the development of the acquired clonal hemolytic and bone marrow failure disorder, paroxysmal nocturnal hemoglobinuria (PNH). Two recent phase 3 clinical studies have demonstrated significant benefit of the complement inhibitor eculizumab (Soliris) in a heterogeneous population of patients with PNH (n=140). Methods: To investigate whether eculizumab was safe and effective in PNH patients with a history of MDS or AA (n=37), efficacy parameters were examined in the MDS/AA patient subpopulation. Results: Intravascular hemolysis, as assessed by plasma levels of the enzyme lactate dehydrogenase (LDH), was reduced from a mean of 1871 ± 159 U/L at baseline to 300 ± 21 U/L at week 26 in patients with a history of MDS or AA (p&lt;0.001, signed rank test; normal range 103–223 U/L). Anemia was improved as packed RBC transfusion requirements were substantially reduced with eculizumab in these patients from a median of 8 units per patient in the 6 months before treatment to 0 units per patient during eculizumab treatment (p&lt;0.001, signed rank test). Despite history of bone marrow failure, eculizumab treatment markedly improved fatigue with an 11.6 point increase over baseline using the FACIT-Fatigue instrument (p&lt;0.001, signed rank test; a 3 or more point increase in this instrument has been shown to be clinical meaningful). Fatigue was similarly improved with the fatigue scale of the EORTC QLQ-C30 instrument (p&lt;0.001, signed rank test). Eculizumab appeared to be well tolerated when administered to PNH patients with a history of MDS or AA. The significant clinical improvements in hematologic and quality of life outcomes with eculizumab treatment in PNH patients with a history of MDS or AA were similar to the clinical improvements demonstrated the overall PNH patient population. Conclusions: These analyses show that eculizumab treatment may provide important clinical benefit when administered to PNH patients with a history of bone marrow failure. No significant financial relationships to disclose.
RON splice variant prevalence in human tumors
Authors: Mark Wortinger, Ling Liu
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3610 

RON ( recepteur d’origine nantais ) is a receptor tyrosine kinase of the MET family and a receptor for macrophage stimulating protein (MSP). RON was found to play a vital role in embryonic development and has also been implicated in tumor progression and metastasis. The RON pathway may be activated in a ligand-independent manner by overexpression of RON or its splice variants, resulting in increased proliferation, motility, and tumor formation. It has been found that reduction of RON expression through binding by antibodies has been successful in inhibiting tumor growth in vivo . Some RON splice variants, however, do not localize to the cell surface and are therefore incapable of being targeted by antibodies. There have been limited literature reports of RON splice variant prevalence in human tumors with variable results. The objective of this study was to characterize the frequency of RON wildtype, p165, p160, and p155 transcripts in human tumors in order to determine if RON splice variants could be a significant cause of RON pathway activation in human tumors. Commercial cDNA panels from six types of human tumors with accompanied normal adjacent tissue samples were used to determine RON splice variant prevalence by PCR. RON mRNA expression differences were clearly seen between tumor types with lung, gastroesophogeal, and colon tissues (both normal and cancerous) having a higher frequency of RON mRNA expression than breast, prostate, and ovarian tissues (both normal and cancerous). RON transcripts favored wildtype and the p165 variant, which were most prevalent and almost always co-expressed. Variants p160 and p155 had progressively lower frequency, respectively. This pattern of RON transcript distribution did not vary significantly in normal adjacent tissue or in the six cancer types measured. Colon, ovarian, and breast cancer tissues had increased RON prevalence compared with accompanied normal adjacent tissue with increases observed for all studied RON transcripts. In only one of the six tumor types studied, colon, was a higher intensity of RON mRNA expression observed in tumor samples compared to normal samples, suggesting RON overexpression in colon tumors. In summary, RON transcripts had a higher expression in both tumor and normal adjacent tissue than expected. For half of the tumor types studied, increased RON mRNA expression was detected in tumor tissue compared with normal tissue; however, this increase was observed for both the alternatively spliced and the wildtype RON transcripts.
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
Authors: Yong Zhang, Dailing Mao, William T Roswit, Xiaohua Jin, Anand C Patel, Dhara A Patel, Eugene Agapov, Zhepeng Wang, Rose M Tidwell, Jeffrey J Atkinson, Guangming Huang, Ronald McCarthy, Jinsheng Yu, Nadezhda E Yun, Slobodan Paessler, T Glen Lawson, Natalie S Omattage, Tom J Brett, Michael J Holtzman
Journal: Nature Immunology (2015)
Myeloperoxidase: A potential marker in low-grade epithelial ovarian carcinoma.
Authors: A. Semaan, S. Sethi, S. Bandyopadhyay, A. Munkarah, R. Ali-Fehmi
Journal: Journal of Clinical Oncology (2010)

e15531 Background: Myeloperoxidase (MPO) is a heme protein synthesized during myeloid differentiation. It is an enzymatic mediator of several inflammatory cascades. A link between inflammation and cancer has long been recognized. We have detected MPO expression in a number of epithelial ovarian cancer cell lines and found that MPO silencing affects cancer cell apoptosis. The aim of this study is to analyze the pattern of MPO expression in a cohort of ovarian carcinomas (OC) (Type I and Type II). Methods: Using our database, we identified 210 patients diagnosed with OC (1992-2002). Paraffin blocks were available for only 175 cases. Patients data and tumor characteristics were retrieved from a review of medical records and SEER database. Tissue microarray sections were immunostained for MPO using DAKO antibody A0398. Cases were categorized as Type I and Type II based on histopathology review and FIGO criteria. 20 benign ovarian specimens, obtained from cases that had salpingo-oophorectomy for benign uterine pathology were used as a control. Cases were considered positive when stain occurred in > 10% of the tumor cells. Statistical analysis was calculated using Chi-square and T test. Results: Of 175 patients, 53 cases were Type I and 122 were Type II. 74% of the cases were serous, 6% mucinous, 4.5% clear cell, 4% mixed serous and mucinous, and 1.5% endometriod. MPO expression was assessed by analyzing cytoplasmic granular staining in tumor cells. Positive staining was noted in endothelial cells and neutrophils, which were used as internal control. MPO expression was significantly more frequent in Type I tumors. In fact, this was noted in 68% in Type I tumors comparing to 38% of Type II cases (p=0.00). On the other hand, no expression was seen in the control benign specimens. Conclusions: MPO expression is detected in ovarian carcinoma but is more frequent in Type 1 tumors. The significance of this expression in the pathogenesis and progression of OC deserve further investigation. Type I (%) Type II (%) Total (%) (MPO) negative 17 (32) 76 (62) 93 (53) (MPO) positive 36 (68) 46 (38) 82 (47) Total 53 122 175 (100) No significant financial relationships to disclose.
Impact of immunogenetic factors to tuberculosis of intrathoracic lymph nodes in children in northwestern Russia
Authors: Anna Starshinova, Maria Pavlova, Irina Dovgaluk, Irina Pavlova, Ludmila Bubnova
Journal: European Respiratory Journal (2012)

Severity of the disease depends not only on peculiarities of causative agent but also on genetic profile of patients. The aim of the study: to study the distribution of HLA-DRB1* alleles in children with tuberculosis of intrathoracic lymph nodes in North-western region of Russia. Totally 188 children from 1 to 15 years old were included in this study. They were divided into two groups. First group of children (n=90) was infected MBT according to tuberculin test, but without clinical signs. The second group (n=98) have tuberculosis of intrathoracic lymphatic nodes. Comparative group (control) consisted of 346 healthy residents of North-western region of Russia. HLA- DRB1* alleles were studied using PCR-SSP method.Statistical analysis was performed using chi-square criterion with Yates correction. The comparative analysis revealed statistically significant difference in HLA- DRB1* alleles' distribution between both investigated groups and control group, at the same time no difference between two investigated groups was revealed. Children of the second group (with tuberculosis of intrathoracic lymphatic nodes tuberculosis) have the frequency of HLA- DRB1*04 significantly higher (36,7% vs. 21,1%, chi-square 10,08; p=0,01) in comparison with control group, while frequency of HLA- DRB1*15 was significantly lower(18,4% vs.28,3%, chi-square 3,9; p=0,05) in this group in comparison with the control group. The results suggest that HLA DRB1*04 may be considered as immunogenetic marker of susceptibility to tuberculosis of intrathoracic lymph nodes, while HLA- DRB1 *15 may be associated with resistance to this disease in children of North-western region of Russia.
Distribution of hobo transposable elements in the genus Drosophila.
Authors: S B Daniels, A Chovnick, I A Boussy
Journal: Molecular Biology and Evolution (1990)

This study describes the distribution of hobo-hybridizing sequences in the genus Drosophila. Southern blot analysis of 134 species revealed that hobo sequences are limited to the melanogaster and montium subgroups of the melanogaster-species group. Of the hobo-bearing species, only D. melanogaster and two of its sibling species, D. simulans and D. mauritiana, were found to contain potentially complete hobo elements. The distribution of hobo sequences is one of the narrowest distributions thus far described for any Drosophila transposable element.
The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL
Authors: Jessica Kristine Nelson, Vincenzo Sorrentino, Rossella Avagliano Trezza, Claire Heride, Sylvie Urbe, Ben Distel, Noam Zelcer
Journal: Circulation Research (2015)

The low-density lipoprotein (LDL) receptor (LDLR) is a central determinant of circulating LDL-cholesterol and as such subject to tight regulation. Recent studies and genetic evidence implicate the inducible degrader of the LDLR (IDOL) as a regulator of LDLR abundance and of circulating levels of LDL-cholesterol in humans. Acting as an E3-ubiquitin ligase, IDOL promotes ubiquitylation and subsequent lysosomal degradation of the LDLR. Consequently, inhibition of IDOL-mediated degradation of the LDLR represents a potential strategy to increase hepatic LDL-cholesterol clearance.To establish whether deubiquitylases counteract IDOL-mediated ubiquitylation and degradation of the LDLR.Using a genetic screening approach, we identify the ubiquitin-specific protease 2 (USP2) as a post-transcriptional regulator of IDOL-mediated LDLR degradation. We demonstrate that both USP2 isoforms, USP2-69 and USP2-45, interact with IDOL and promote its deubiquitylation. IDOL deubiquitylation requires USP2 enzymatic activity and leads to a marked stabilization of IDOL protein. Paradoxically, this also markedly attenuates IDOL-mediated degradation of the LDLR and the ability of IDOL to limit LDL uptake into cells. Conversely, loss of USP2 reduces LDLR protein in an IDOL-dependent manner and limits LDL uptake. We identify a tri-partite complex encompassing IDOL, USP2, and LDLR and demonstrate that in this context USP2 promotes deubiquitylation of the LDLR and prevents its degradation.Our findings identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL.
Randomized Clinical Trial of Adjuvant Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy for Patients With Fast-Proliferating, Node-Negative Breast Cancer
Authors: Angelo Paradiso, Francesco Schittulli, Giovanni Cellamare, Annita Mangia, Franco Marzullo, Vito Lorusso, Mario De Lena
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The prospective applicability of new biologic tumor information to personalize adjuvant treatment of women with operable breast cancer remains to be demonstrated. The aim of the present study was to investigate whether patients with fast-proliferating, node-negative breast cancer could benefit from adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS AND METHODS: Beginning in November 1989, we analyzed the proliferative activity of primary tumors in a consecutive series of women with node-negative breast cancer to identify subgroups of patients with a worse prognosis and who were therefore suitable candidates for adjuvant systemic therapy. Proliferative activity was determined by means of the [ 3 H]-thymidine incorporation assay using an autoradiographic technique. Women with fast-proliferating breast cancer ([ 3 H]-thymidine labeling index, &gt; 2.3%) were randomized to receive either six cycles of adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One-hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2, N0, M0 breast cancer were randomized to the FEC and control arms, respectively. After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC arm and 39 (32.2%) in the control arm, with a significantly lower number of locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was 81% in the FEC group and 69% in the control group (P &lt; .02 by log-rank test). Cox multivariate analysis described the impact of adjuvant therapy with FEC on DFS as independent of the patients’ main clinical-pathologic characteristics. CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the clinical outcome of patients with fast-proliferating, node-negative breast cancer.
Which COPD patients should be admitted to the ICU
Authors: C Subbe
Journal: Thorax (2009)

A total of 832 patients with obstructive lung disease aged 45 years and older were prospectively recruited from 92 intensive care units and 3 respiratory high-dependency units in the UK. Detailed physiological and functional data were collected on admission to intensive care and they were followed up for 180 days.

Mortality at 180 days was 37.9%. A scoring system was …
Orchiectomy has fewer adverse effects than chemical castration for metastatic prostate cancer
Authors: Jacqui Wise
Journal: BMJ (2015)

Medical castration is associated with a higher risk of adverse effects than surgical castration in men with metastatic prostate cancer, research published in JAMA Oncology has found.1

Androgen deprivation therapy is a mainstay in the treatment of prostate cancer and can be achieved either surgically or pharmacologically with gonadotrophin releasing hormone analogues (GnRHa). In recent years medical castration has largely replaced …
Assortment of drugs causes more problems than it solves
Authors: B. Van Der Heide, E. Schouten
Journal: BMJ (1995)

EDITOR,—It is estimated that between 5% and 40% of the drugs that are sold in pharmacies in western Europe are not used.1 Although the legal framework in the European Union prohibits the collection and export of drugs that have been issued to patients and returned to pharmacies, practice shows that there are many loopholes in the legislation and control.

Several non-government organisations have carried out public campaigns to promote the collection of unused drugs for humanitarian purposes, with slogans such as “giving an unused drug will save …
A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy
Authors: Jung-Yoon Choe, Nenad Prodanovic, Jaroslaw Niebrzydowski, Ivan Staykov, Eva Dokoupilova, Asta Baranauskaite, Roman Yatsyshyn, Mevludin Mekic, Wieskawa Porawska, Hana Ciferska, Krystyna Jedrychowicz-Rosiak, Agnieszka Zielinska, Jasmine Choi, Young Hee Rho, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. <h3>Methods</h3> This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. <h3>Results</h3> 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. <h3>Conclusions</h3> SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. <h3>Trial registration number</h3> NCT01936181.