tbuckley/cabot-search huggingface dataset:
Why African Americans are more predisposed to pancreatic cancer: Nature versus nurture.
Authors: Wesley Thompson, Naeem Latif, Robert Rahberg
Journal: Journal of Clinical Oncology (2013)

e15018 Background: There are known risk factors for pancreatic cancer like diabetes mellitus; cigarette smoking; poverty, and alcoholism; all of which are more common in African American patients than the general population. The purpose was to determine if these established risk factors were more associated within African American pancreatic cancer patients to explain their 50 – 90% increased incidence in the U.S. population. Methods: This retrospective study reviewed 172 biopsy-proven pancreatic cancer patients diagnosed over ten years at University of Florida Jacksonville. We employed linear regression models to determine statistical significance of established risk factors with prevalence of pancreatic cancer among cohorts. Results: Our data showed no increased association of diabetes, tobacco use, alcohol use between African Americans and Caucasians. However, Africans Americans as a group were twice as likely to be found at stage III or IV upon diagnosis, conferring an increased mortality risk (OR = 2.2, (95% CI 1.1 – 4.39)). Among these African Americans at advanced stage of diagnosis, females were at triple risk by odds ratio to be underinsured compared to Caucasian males (OR = 3.1, (95% CI 1.29 – 7.49, p = 0.015)). African American females were almost twice as likely to be underinsured compared to Caucasian females (OR = 1.72, (95% CI 0.646, 4.558)). The lack of healthcare access maybe related to advanced stage at diagnosis and its increased mortality risk. Conclusions: Our data suggests that the risk factors of smoking, alcoholism, and diabetes mellitus alone do not explain African Americans’ propensity for pancreatic cancer. However, lack of health insurance does confer an advanced stage at diagnosis and increased mortality risk among African American females. Our data also suggests that other etiological factors such as genetics maybe be associated with the increased risk amongst African Americans. A further investigation is warranted into genetic etiologies since African American patients have higher incidence of K-ras mutations than Caucasians; and mutated K-ras has been associated with pancreatic cancer, which is a target for therapy.
Abstract P069: The Relationship of Serum Marine-Derived N-3 Fatty Acids and Carotid Intima-Media Thickness among General Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)
Authors: Aya Kadota, Akira Sekikawa, Katsuyuki Miura, Tomonori Okamura, Akira Fujiyoshi, Takashi Kadowaki, Emma Barinas-Mitchell, Rhobert W Evans, Takayoshi Ohkubo, Takashi Hisamatsu, Naoko Miyagawa, Yasuyuki Nakamura, Hiroshi Maegawa, Atsunori Kashiwagi, Hirotsugu Ueshima
Journal: Circulation (2013)

Objective Anti-atherosclerotic properties of marine-derived n-3 fatty acids (MDn3FA) remain controversial. We examined the relationship of serum MDn3FA and carotid intima-media thickness (IMT) in g...
Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis
Authors: Jingxiao Wang, Haichuan Wang, Michele Peters, Ning Ding, Silvia Ribback, Kirsten Utpatel, Antonio Cigliano, Frank Dombrowski, Meng Xu, Xinyan Chen, Xinhua Song, Li Che, Matthias Evert, Antonio Cossu, John Gordan, Yong Zeng, Xin Chen, Diego F. Calvisi
Journal: Journal of Hepatology (2019)
Noncontrast CMR for Detecting Early Myocardial Tissue Injury in a Swine Model of Anthracycline-Induced Cardiotoxicity
Authors: Shiro Nakamori, Jihye Jang, Cory M. Tschabrunn, Patrick Pierce, Beth Goddu, Jennifer Rodriguez, Long H. Ngo, Nadine M. Tung, Warren J. Manning, Reza Nezafat
Journal: JACC. Cardiovascular imaging (2019)
Novel Therapies for Prevention and Early Treatment of Cardiomyopathies
Authors: Giuliana G. Repetti, Christopher N. Toepfer, Jonathan G. Seidman, Christine E. Seidman
Journal: Circulation Research (2019)

Heritable cardiomyopathies are a class of heart diseases caused by variations in a number of genetic loci. Genetic variants on one allele lead to either a degraded protein, which causes a haploinsufficiency of that protein, or a nonfunctioning protein that subverts the molecular system within which the protein works. Over years, both of these mechanisms eventually lead to diseased heart tissue and symptoms of a failing heart. Most cardiomyopathy treatments repurpose heart failure drugs to manage these symptoms and avoid adverse outcomes. There are few therapies that correct the underlying pathogenic genetic or molecular mechanism. This review will reflect on this unmet clinical need in genetic cardiomyopathies and consider a variety of therapies that address the mechanism of disease rather than patient symptoms. These therapies are genetic, targeting a defective gene or transcript, or ameliorating a genetic insufficiency. However, there are also a number of small molecules under exploration that modulate downstream faulty protein products affected in cardiomyopathies.
Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS
Authors: Henrik Knecht, Tomas Reigl, Michaela Kotrová, Franziska Appelt, Peter Stewart, Vojtech Bystry, Adam Krejci, Andrea Grioni, Karol Pal, Kamila Stranska, Karla Plevova, Jos Rijntjes, Simona Songia, Michael Svatoň, Eva Froňková, Jack Bartram, Blanca Scheijen, Dietrich Herrmann, Ramón García-Sanz, Jeremy Hancock, John Moppett, Jacques J. M. van Dongen, Giovanni Cazzaniga, Frédéric Davi, Patricia J. T. A. Groenen, Michael Hummel, Elizabeth A. Macintyre, Kostas Stamatopoulos, Jan Trka, Anton W. Langerak, David Gonzalez, Christiane Pott, Monika Brüggemann, Nikos Darzentas
Journal: Leukemia (2019)

Assessment of clonality, marker identification and measurement of minimal residual disease (MRD) of immunoglobulin (IG) and T cell receptor (TR) gene rearrangements in lymphoid neoplasms using next-generation sequencing (NGS) is currently under intensive development for use in clinical diagnostics. So far, however, there is a lack of suitable quality control (QC) options with regard to standardisation and quality metrics to ensure robust clinical application of such approaches. The EuroClonality-NGS Working Group has therefore established two types of QCs to accompany the NGS-based IG/TR assays. First, a central polytarget QC (cPT-QC) is used to monitor the primer performance of each of the EuroClonality multiplex NGS assays; second, a standardised human cell line-based DNA control is spiked into each patient DNA sample to work as a central in-tube QC and calibrator for MRD quantification (cIT-QC). Having integrated those two reference standards in the ARResT/Interrogate bioinformatic platform, EuroClonality-NGS provides a complete protocol for standardised IG/TR gene rearrangement analysis by NGS with high reproducibility, accuracy and precision for valid marker identification and quantification in diagnostics of lymphoid malignancies.
Abstract 19208: Unplanned Readmissions in Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Nationwide Perspective
Authors: Ashish Correa, Priti Poojary, Aparna Saha, Kinsuk Chauhan, Shanti Patel, Girish N Nadkarni
Journal: Circulation (2017)

Background: Readmissions after hospitalizations for acute myocardial infarctions (AMI) managed with percutaneous coronary intervention (PCI) are quite common, form a major healthcare burden to a vu...
BuddySuite: Command-Line Toolkits for Manipulating Sequences, Alignments, and Phylogenetic Trees
Authors: Stephen R. Bond, Karl E. Keat, Sofia N. Barreira, Andreas D. Baxevanis
Journal: Molecular Biology and Evolution (2017)

The ability to manipulate sequence, alignment, and phylogenetic tree files has become an increasingly important skill in the life sciences, whether to generate summary information or to prepare data for further downstream analysis. The command line can be an extremely powerful environment for interacting with these resources, but only if the user has the appropriate general-purpose tools on hand. BuddySuite is a collection of four independent yet interrelated command-line toolkits that facilitate each step in the workflow of sequence discovery, curation, alignment, and phylogenetic reconstruction. Most common sequence, alignment, and tree file formats are automatically detected and parsed, and over 100 tools have been implemented for manipulating these data. The project has been engineered to easily accommodate the addition of new tools, is written in the popular programming language Python, and is hosted on the Python Package Index and GitHub to maximize accessibility. Documentation for each BuddySuite tool, including usage examples, is available at http://tiny.cc/buddysuite_wiki. All software is open source and freely available through http://research.nhgri.nih.gov/software/BuddySuite.
Metronidazole-sensitive organisms in children with severe acute malnutrition: an evaluation of the indication for empiric metronidazole treatment
Authors: M. Zangenberg, A. Abdissa, Ø.H. Johansen, G. Tesfaw, T. Girma, J.A.L. Kurtzhals
Journal: Clinical Microbiology and Infection (2019)

Children with severe acute malnutrition (SAM) are treated with empiric amoxicillin or penicillin and gentamicin because of the high risk of severe infections. Experts have suggested, based on available evidence, adding metronidazole to cover anaerobic bacteraemia and diarrhoea caused by Giardia duodenalis or Clostridium difficile. The objective of this study was to assess the importance of these infections in children with SAM.Children from 6 months to 15 years with SAM were enrolled and followed clinically. Aerobic and, when patient weight permitted, anaerobic blood cultures were done using Bactec® system, and isolates identified with matrix-assisted laser desorption ionization-time of flight mass spectrometry. Stool samples were tested for C. difficile, G. duodenalis and Entamoeba histolytica by PCR.A total of 334 children were enrolled and 174 out of 331 (53%) for which data on this was available had diarrhoea. Of 273 patients tested by blood culture, 11 had bacteraemia (4.0%, 95% CI 2.3-7.1%) but none with strict anaerobic bacteria (0/153, 95% CI 0-2.4%). There was no difference in the prevalence of C. difficile between children with (5/128, 4%) and without (7/87, 8%) diarrhoea (OR 0.47, 95% CI 0.14-1.53), and no difference in the prevalence of Giardia between these groups (78/138, 60% vs. 46/87, 53%; OR 1.34, 95% CI 0.77-2.32). Children with C. difficile had higher mortality than those without this infection (3/11, 27%, vs. 7/186, 4%; OR 43, 95% CI 3.9-483).Our results do not provide support for empiric metronidazole to cover for anaerobic bacteraemia. Trials evaluating the effect of empiric treatment and its effect on G. duodenalis and C. difficile are warranted.
An Artificial Intelligence Approach for B Lymphoblastic Leukemia Minimal Residual Disease Detection and Clinical Prognosis Prediction Using Flow Cytometry Data
Authors: Yu-Fen Wang, Bor-Sheng Ko, Chi-Cheng Li, Jeng-Lin Li, Pei-Fang Weng, Huai-Hsuan Huang, Hsin-An Hou, Hwei-Fang Tien, Chi-Chun Lee, Jih-Luh Tang
Journal: Blood (2017)
Alcohol sales fall in Scotland a year after minimum pricing took effect
Authors: Bryan Christie
Journal: BMJ (2019)

Sales of alcohol in Scotland have fallen to their lowest recorded level in the year since the price of cheap drinks was increased to curb the harm caused by alcohol.

Although it is too early to draw clear conclusions about the effect of minimum unit pricing, the figures on alcohol sales are being seen as positive. 

Scotland introduced a minimum price of 50p a unit for alcohol in May last year after a six year legal battle with the drinks industry.1 Modelling carried out on behalf of the Scottish government indicated that higher prices of …
Abstract #4662: Survivin knockdown enhanced efficacy of N-(4-hydroxyphenyl) retinamide for apoptosis in human glioblastoma U138MG and U251MG cells and inhibited invasion, angiogenesis, and tumor growth
Authors: Joseph George, Naren Banik, Swapan Ray
Journal: Cancer Research (2009)

Upregulation of the anti-apoptotic molecule survivin inhibits apoptosis and promotes tumor growth. Survivin is selectively upregulated in various cancers including glioblastoma, which is the most malignant brain tumor characterized by high angiogenesis, invasion, and cell proliferation. Treatment of cancer cells with N-(4-hydroxyphenyl) retinamide (4-HPR) induces apoptosis due to destabilization of mitochondrial membrane and activation of caspase mediated apoptotic pathways. In the present investigation, we examined whether survivin knockdown using cognate siRNA could enhance efficacy of 4-HPR for apoptosis in human glioblastoma U138MG and U251MG cells and inhibit cell invasion, angiogenesis, and tumor growth in athymic nude mice. Using a plasmid vector expressing cognate siRNA, we down regulated expression of survivin in both U138MG and U251MG cells and simultaneously treated them with 1 \#956;M 4-HPR for 48 h. Following the treatment of cells, we performed MTT assay, double immunofluorescent staining, TUNEL staining, FACS analysis, and matrigel invasion assay. We also carried out Western blotting for examining the molecules involved in caspase mediated apoptotic pathways. Double immunofluorescent stainings showed marked decrease in survivin expression and conspicuous increase in active caspase-3 after transfection of cells with survivin siRNA and treatment with 4-HPR. Both TUNEL staining and FACS analysis demonstrated apoptosis in more than 80% of cells after treatment with combination of both agents. MTT assay and invasion studies demonstrated marked decreases in tumor cell proliferation and invasion, respectively. Thereafter, we performed in vivo angiogenesis and tumor regression studies in athymic nude mice. Angiogenesis studies under the dorsal skin of athymic nude mice depicted remarkable inhibition of neovascularization after treatment with combination of survivin siRNA and 4-HPR. In vivo imaging studies on intracerebral and subcutaneous tumorigenesis and also longitudinal studies on solid tumor development showed marked decreases in tumorigenesis and solid tumor development after treatment with combination of survivin siRNA and 4-HPR. Therefore, simultaneous survivin knockdown using cognate siRNA and 4-HPR treatment could be a novel therapeutic strategy for controlling growth of human glioblastomas. This investigation was supported in part by the R01 grants (CA-91460 and NS-57811) from the National Institutes of Health (Bethesda, MD).  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4662.
PB2086 LOW RISK MYELODYSPLASTIC SYNDROMES (LRMDS) RESPONSE TO ERYTHROPOIETIN MIGHT BE ENHANCED BY DIFFERENT IRON FORMULATION INFLUENCING BONE MARROW METILATION PATTERNS AND MACROPHAGES POLARIZATION
Authors: G. Giordano, A. Lucchesi, M. magri, G. niro, M. gasperi
Journal: HemaSphere (2019)

Background: Iron status influences dna methylation. External factors as liposomes may switc‐off bone marrow macrophages M1 polarization that is related to inflammatory status. These things are important in ineffective hemopoiesis in LRMDS. Aims: To see if sucromial iron and sodium ferrigluconate support in LRMDS shows different dna metilation patterns and macrophages polarization in bone marrow. Methods This study is a retrospective nonrandomized study. 45 patients with low risk refractory anemia receiving support with erythropoietin 40000 UI two times/week, b12 300 mg/day and folate 15 mg/day were divided in 3 group of 15 patients. Group A received i.v. sodium ferrigluconate 65 mg/day for 7 days/month, group B received sucrosomial iron tablets every other day, group C don’t received iron. No significant differences among median Hb level (9.5 g/dl), median age (65 yo), sex, karyotype, sEpo, ferritin, Tsat, IPSS, transfusion need, were in the three groups. Follow‐up period was 6 months. The bone marrow M1 proinflammatory macrophages (iNOS high /CD163 low /CD14 + ) and M2 antiinflammatory (iNOS low /CD163 high /CD14‐) were analyzed by cytofluorimetry and dna methylation with methylation‐specific PCR. Bone marrow aspiration, M1 and M2 count, dna methylation, Hb level, transfusion need, ferritin and tsat level, CRP were recorded bimonthly. Results: All results were recorded at time 0, 2, 4 and 6 months. M1% was 1, 0.8, 0.7, 1 in group A, 1.2, 0.9, 0.6, 0.4 in group B, 0.8, 0.8, 0.9, 1 in group C. M2% was0.4, 0.5, 0.3, 0.4 in group A, 0.4, 0.5, 0.5,0.6 in group B, 0.3, 0.3, 0.4,0.3 in group C. % of methilated cytosine was 6% in group A, 3% in group B, 5% in group C. CRP (ng/ml) was 6, 8, 10, 12 in group A, 7, 5, 3, 2 in group B, 8, 6, 5, 5 in group C. Hb concentration (g/dl) was 9, 9.8, 11.5, 11.8 in group A, 9, 10.2, 11.5, 12.5 in group B, 9.5, 10, 10.5, 10.9 in group C. Transfusion need (units) was 2 in group A, 2 in group B, 2 in group C. Summary/Conclusion: In LRMDS iron support improves erythropoietin effectiveness and reduces dna methylation. Sucrosomial iron reduces macrophages M1 polarization and CRP, improving effective hemopoiesis. image
FRI0027 PROGNOSTIC MARKERS FOR PRECLINICAL CARDIOVASCULAR DISEASE IN RHEUMATOID ARTHRITIS AND CORRELATION WITH DISEASE ACTIVITY
Authors: Annelies Blanken, Rabia Agca, C.J. van der Laken, Michael Nurmohamed
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with rheumatoid arthritis (RA) have an elevated cardiovascular (CV) disease risk, explained both by an increased prevalence of traditional CV risk factors and the presence of chronic systemic inflammation that impairs vascular function, leads to thickening of the arterial wall and increased arterial stiffness. <h3>Objectives:</h3> In this study we investigated the effect of anti-inflammatory treatment on prognostic markers for preclinical cardiovascular disease (arterial wall thickening and arterial stiffness) and the correlation of these markers with RA disease parameters. <h3>Methods:</h3> Carotid ultrasound (using Artlab echotracking system) was used to determine carotid intima media thickness (IMT) and pulse wave analysis was done with SphygmoCor tonometry to calculate pulse wave velocity (PWV) and augmentation index (AIx). Paired t-test was used to compare PWV, AIx and IMT prior and after 6 months of therapy. Pearson correlation was calculated to investigated the correlation of PWV, AIx and IMT with (natural logarithm of) C-reactive protein (CRP), (natural logarithm of) erythrocyte sedimentation rate (ESR) and disease activity score-28 (DAS28). For correlations, data from both time points were pooled. <h3>Results:</h3> In total 61 consecutive RA patients (50% early arthritis starting with csDMARD and 50% established RA starting with adalimumab) were asked to undergo arterial analysis just prior to start of therapy and after 6 months. PWV was performed in 45 patients at baseline and 39 at follow-up, IMT in 56 and 45 patients respectively and AIx in 51 and 44 patients respectively. Both signs of arterial stiffness (PWV and AIx) decreased after 6 months of therapy (mean difference 0.7 and 0.8 respectively; table 1), although this did not reach statistical significance. IMT remained stable during 6 months of therapy. <h3>Conclusion:</h3> Arterial stiffness as measured with PWV tended to decrease after 6 months of anti-inflammatory treatment. Arterial stiffness and arterial intima media thickness correlated with clinical disease parameters. Altogether, these changes might suggest that effective antirheumatic therapy has favorable cardiovascular effects. Whether or not this ultimately leads to a significant reduction of "hard" cardiovascular endpoints remains to be established in prospective studies. <h3> Disclosure of Interests: </h3> Annelies Blanken: None declared, Rabia Agca: None declared, C.J. van der Laken: None declared, Michael Nurmohamed Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB
FRI0126 THE INFUSION-RELATED REACTIONS OF RITUXIMAB IN RHEUMATIC DISEASES: SINGLE-CENTER EXPERIENCE OF 1893 INFUSIONS OVER 5 YEARS
Authors: Kung-Yu Wang, Cheng-Hsun Lu, Chiao-Feng Cheng, Song-Chou Hsieh, LI Ko-Jen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rituximab has been used for treating autoimmune disease. To date, the infusion-related reaction has been mainly studied in patients with hematological malignancy, and there is limited data for rheumatic diseases. <h3>Objectives</h3> We accessed the incidence rate of infusion-related reactions (IRR) of rituximab (RTX) including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), dermatomyositis and polymyositis (PDM), as well as systemic sclerosis (SSc). <h3>Methods</h3> We included all patients with diagnosis of RA, SLE, SjS, PDM or SSc, whose first cycle of RTX therapy during January 2013 to December 2017. Each cycle of RTX consisted of 2 infusions of RTX (500-1000 mg), with combination of methylprednisolone (80-100 mg) with or without antihistamines. The infusion-related reaction was defined as the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Frequency and severity of IRR in each infusion were compared between different diseases and cycles. Logistic regression was applied for cross-sectional data analysis, and generalized estimating equations were used for longitudinal data analysis. <h3>Results</h3> Totally, 336 patients were included as shown in table 1. There were 100 IRRs out of 1893 infusions, among which 37 were at the first time of RTX infusion. Patients with SjS had showed higher rate of IRR in the first infusion compared with other disease (19.1% vs 8.1%, p=0.008). Considering grade 2 or more severe IRRs, patients with SjS still has higher IRR (p=0.004). SjS was an independent risk for developing IRR (OR 2.5, 95% CI 1.3-4.7, p=0.006). Seventy (78.7%) of the patients with SjS had positive anti-SSA antibody, but the presence of anti-SSA antibody was not a significant risk for IRR after controlling for the diagnosis of SjS. The IRR per infusion was not related to the RTX dose. The IRR in an infusion did not led to stopping of the therapy, although infusion rate and premedication can be adjusted in the following therapies. Only 39.6% of the patients with an IRR had suffer from more IRR in the following infusions. Besides, male gender and the increasing cycles were associated with less IRR (p=0.029 and 0.007, respectively). In the 100 patients received more than 4 cycles, the rate of IRR decreased along with the cycles. No life-threatening IRR happened in the 1893 infusions. <h3>Conclusion</h3> Our study had found that patients with SjS had higher IRR compared to other diseases. Female had more frequent IRR might due to the sexual distribution of these diseases. <h3>Acknowledgement</h3> NA <h3>Disclosure of Interests</h3> None declared