tbuckley/cabot-search huggingface dataset:
Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated October 2017
Authors: Jean-Marc Dumonceau, Andrea Tringali, Ioannis Papanikolaou, Daniel Blero, Benedetto Mangiavillano, Arthur Schmidt, Geoffroy Vanbiervliet, Guido Costamagna, Jacques Devière, Jesús García-Cano, Tibor Gyökeres, Cesare Hassan, Frédéric Prat, Peter Siersema, Jeanin van Hooft
Journal: Endoscopy (2018)

Main Recommendations ESGE recommends against routine preoperative biliary drainage in patients with malignant extrahepatic biliary obstruction; preoperative biliary drainage should be reserved for patients with cholangitis, severe symptomatic jaundice (e. g., intense pruritus), or delayed surgery, or for before neoadjuvant chemotherapy in jaundiced patients. Strong recommendation, moderate quality evidence. ESGE recommends the endoscopic placement of a 10-mm diameter self-expandable metal stent (SEMS) for preoperative biliary drainage of malignant extrahepatic biliary obstruction. Strong recommendation, moderate quality evidence. ESGE recommends SEMS insertion for palliative drainage of of extrahepatic malignant biliary obstruction. Strong recommendation, high quality evidence. ESGE recommends against the insertion of uncovered SEMS for the drainage of extrahepatic biliary obstruction of unconfirmed etiology. Strong recommendation, low quality evidence. ESGE suggests against routine preoperative biliary drainage in patients with malignant hilar obstruction. Weak recommendation, low quality evidence. ESGE recommends uncovered SEMSs for palliative drainage of malignant hilar obstruction. Strong recommendation, moderate quality evidence. ESGE recommends temporary insertion of multiple plastic stents or of a fully covered SEMS for treatment of benign biliary strictures. Strong recommendation, moderate quality evidence. ESGE recommends endoscopic placement of plastic stent(s) to treat bile duct leaks that are not due to transection of the common bile duct or common hepatic duct. Strong recommendation, moderate quality evidence.
Risk of High Blood Pressure Among Young Men Increases With the Degree of Immaturity at Birth
Authors: StefanJohansson, AnastasiaIliadou, NiklasBergvall, TorstenTuvemo, MikaelNorman, SvenCnattingius
Journal: Circulation (2005)

Background— Survivors of preterm birth constitute a new generation of young adults, but little is known about their long-term health. We investigated the association between gestational age (GA) and risk of high blood pressure (HBP) in young Swedish men and whether GA modified the risk of HBP; ie, whether HBP was related to being born small for gestational age (SGA). Methods and Results— This population-based cohort study included 329 495 Swedish men born in 1973 to 1981 who were conscripted for military service in 1993 to 2001. Multivariate linear- and logistic-regression analyses were performed. Main outcome measures were systolic and diastolic BPs at conscription. Linear-regression analyses showed that systolic BP increased with decreasing GA (regression coefficient −0.31 mm Hg/wk, P<0.001). Systolic and diastolic BPs both increased with decreasing birth weight for GA, but the association with systolic BP was most evident (regression coefficient −0.67 mm Hg per SD score in birth weight for GA, P<0.001)...
Abstract 2244: Differential DNA methylation analysis of TCGA cholangiocarcinoma data
Authors: Nitish K. Mishra, Niu Meng, Chittibabu Guda
Journal: Cancer Research (2018)

Abstract Cholangiocarcinoma (CCA), also known as bile duct cancer, is a rare malignancy that develops in bile duct, arising from the epithelial cells (cholangiocytes) lining the bile duct. CCA is the second most common type of primary liver cancer, and its incidence has been rising in the Unites States. Most of the patients with CCA are diagnosed at an advanced stage with a median survival of less than 1 year despite administering chemotherapy. In the current study, we analyze the global patterns of DNA methylation in CCA data from TCGA. Pathway and gene ontology (GO) enrichment analysis of differentially methylated genes (DMGs) enabled us to understand how changes in methylation and gene expression affect the biologic pathways involved in the progression of CCA. TCGA level-3 DNA methylation data were downloaded for 485,578 CpG sites with annotations. Further, we normalized β value by using Beta Mixed Integer-quantile normalization (BMIQ) to adjust type I and type II probes. For a CpG site to be considered differentially methylated, the difference in the median β value in primary tumor and normal samples should be at least 0.2 and the BH adjusted p-value should be less than 0.005 and AUC ≥ 0.7. A total of 12,259 differentially methylated (Δβ &amp;gt;) CpG were observed; out of these 9,534 are hypermethylated and 2,725 are hypomethylated. About 4,714 differentially methylated CpGs (dm-CpGs) were observed within 1.5Kb from the TSS of corresponding genes. Chromosome 1 has maximum number of dm-CpGs, while chromosome 18 has lowest number of dm-CpGs. Differential DNA methylation frequency per Mb was also calculated and it was observed that chromosome 17 has the highest differential methylation frequency (9.61 dm-CpGs/Mb) while chromosome 18 has the lowest (1.47 dm-CpG/Mb). KEGG pathway analysis of genes with differentially methylated CpGs (Δβ ≥ 0.2) observed the enrichment of cancer, cell division and differentiation, amino acid metabolism, xenobiotics degradation, and immune response pathways. Hippo signaling pathway also got affected by DNA methylation (FDR 3.70e-18), which also got affected by differential gene expression. Change in DNA methylation and gene expression level of hippo signaling pathway genes plays a vital role in CCA. Citation Format: Nitish K. Mishra, Niu Meng, Chittibabu Guda. Differential DNA methylation analysis of TCGA cholangiocarcinoma data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2244.
The Roles of Lipid Oxidation Products and Receptor Activator of Nuclear Factor-κB Signaling in Atherosclerotic Calcification
Authors: LindaDemer, YinTintut
Journal: Circulation Research (2011)

This review focuses on the roles of oxylipids and receptor activator of nuclear factor-κB ligand signaling in calcific cardiovascular disease. Both intimal and valvular calcifications are closely associated with atherosclerosis, leading investigators to study the role of atherogenic oxidatively modified lipids (oxylipids). Results have identified the molecular signaling through which oxylipids induce osteogenic differentiation and calcification in vascular cells. A surprising concomitant finding was that, in bona fide osteoblasts from skeletal bone, oxylipids have the opposite effect, ie, inhibiting osteoblastic maturation. This is the basis for the lipid hypothesis of osteoporosis. Oxylipids also induce resorptive osteoclastic cells within the bone environment, raising the question of whether resorptive osteoclasts can be harnessed in the vascular context for cell-based therapy to remove artery wall mineral deposits. The challenge is that vascular cells produce antiosteoclastogenic factors, including the...
Prognostic Value of QT Interval Parameters for Mortality Risk Stratification in Chagas’ Disease
Authors: GilSalles, SergioXavier, AndreaSousa, AlejandroHasslocher-Moreno, ClaudiaCardoso
Journal: Circulation (2003)

Background— QT interval parameters are potential prognostic markers of arrhythmogenicity risk and cardiovascular mortality and have never been evaluated in Chagas’ disease. Methods and Results— Outpatients (738) in the chronic phase of Chagas’ disease were enrolled in a long-term follow-up study. Maximal heart rate-corrected QT (QTc) and T-wave peak-to-end (TpTe) intervals and QRS, QT, JT, QTapex, and TpTe dispersions and variation coefficients were measured manually and calculated from 12-lead ECGs obtained on admission. Clinical, radiological, and 2-dimensional echocardiographic data were also recorded. Primary end points were all-cause, Chagas’ disease-related, and sudden cardiac mortalities. During a follow-up of 58±39 months, 62 patients died, 54 of Chagas’ disease-related causes and 40 suddenly. Multivariate Cox survival analysis revealed that the QT-interval dispersion (QTd) (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.63; P<0.001, for 10-ms increments) and left ventricular (LV) end-syst...
Abstract 358: miRNAs/Ago2/YY1/PcG protein/DNMT complex mediates epigenetic silencing of locus genes and associates with bortezomib-induced apoptosis of leukemia
Authors: Ju-Ming Wang, Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu
Journal: Cancer Research (2018)

Abstract miRNAs are a class of non-coding RNAs, which bind to the 3'-untranslated regions of their target mRNAs to repress translation. However, the details of miRNA-mediated epigenetic regulation targeting genomic DNA remained largely unknown. Here, we demonstrated that transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, is a highly selective reversible inhibitor for leukemia treatment, and resulting in caspase activation and apoptosis. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 feedback to suppress the transcription of CEBPD itself and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Additionally, we previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for mediating epigenetic silencing of the CEBPD gene; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. Moreover, we revealed that miRNA binding plays a key role for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. Altogether, we provided new insights for miRNA-mediated epigenetic regulation in the case of bortezomib-induced cell death in leukemia. Citation Format: Ju-Ming Wang, Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu. miRNAs/Ago2/YY1/PcG protein/DNMT complex mediates epigenetic silencing of locus genes and associates with bortezomib-induced apoptosis of leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 358.
Abstract 1140: Genes preserving stem cell state in group 3 medulloblastoma brain tumor initiating cells contribute to therapy evasion and relapse
Authors: Sheila Kumari Singh, David Bakhshinyan, Chitra Venugopal, Ashley Adile, Mohini Singh, Maleeha Qazi, Branavan Manoranjan, Michelle Kameda-Smith
Journal: Cancer Research (2018)

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Of current molecular subgroups, Group 3 patients face the highest incidence of metastatic spread and overall patient survival of less than 50%. Current clinical trials for recurrent MB patients based on genomic profiles of primary, treatment-naïve tumors provide limited clinical benefit, since recurrent metastatic MBs are highly genetically divergent from their primary tumors. By adapting the existing COG (Children's Oncology Group) protocol for children with newly diagnosed high-risk MB to the treatment of immuno-deficient mice intracranially engrafted with human MB brain tumor initiating cells (BTICs), we have characterized the rare treatment-refractory cell population in Group 3 MBs. MB cell populations recovered separately from brains and spines during the course of tumor development and therapy were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy to relapse. One of the most intriguing observations from our gene expression data was consistent over-expression in the treatment-refractory cell population of proteins belonging to the Inhibitor of DNA-binding/differentiation (ID) family (transcription factors with a basic helix-loop-helix motif that act as suppressors cellular differentiation), and a longevity-associated protein known as bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4). This persistent upregulation of genes preserving undifferentiated state and cellular longevity further strengthens the hypothesis of stem-cell like cells driving tumor relapse in MB. Targeting ID1 and BPIFB4 using both knockdown (KD) and knockout (KO) strategies has resulted in decreased self-renewal and tumorigenicity of both primary and recurrent MB cells, further highlighting their potential as novel therapeutic targets in MB. Our differential genomic and gene expression profiles of the “treatment-responsive” tumors against those that fail therapy have successfully contributed to discovery and characterization of novel therapeutic targets for the most aggressive subgroup of MB. Citation Format: Sheila Kumari Singh, David Bakhshinyan, Chitra Venugopal, Ashley Adile, Mohini Singh, Maleeha Qazi, Branavan Manoranjan, Michelle Kameda-Smith. Genes preserving stem cell state in group 3 medulloblastoma brain tumor initiating cells contribute to therapy evasion and relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1140.
Elevated Placental Soluble Vascular Endothelial Growth Factor Receptor-1 Inhibits Angiogenesis in Preeclampsia
Authors: ShakilAhmad, AsifAhmed
Journal: Circulation Research (2004)

Preeclampsia is an inflammatory disorder in which serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor-1 (sVEGFR-1, also known as sFlt-1) are elevated. We hypothesize that VEGF and placenta growth factor (PlGF) are dysregulated in preeclampsia due to high levels of sVEGFR-1, which leads to impaired placental angiogenesis. Analysis of supernatants taken from preeclamptic placental villous explants showed a four-fold increase in sVEGFR-1 than normal pregnancies, suggesting that villous explants in vitro retain a hypoxia memory reflecting long-term fetal programming. The relative ratios of VEGF to sVEGFR-1 and PlGF to sVEGFR-1 released from explants decreased by 53% and 70%, respectively, in preeclampsia compared with normal pregnancies. Exposure of normal villous explants to hypoxia increased sVEGFR-1 release compared with tissue normoxia (P<0.001), as did stimulation with tumor necrosis factor-α (P<0.01). Conditioned medium (CM) from normal villous explants induced endothelial...
Abstract 3647: Prior DNA repair improves the read quality in next-generation sequencing of cell-free tumor DNA
Authors: Hong Yin, Adam H. Greer, Glenn Mills
Journal: Cancer Research (2018)

Abstract The cell-free tumor DNA (ctDNA) in patient's plasma is a noninvasive tumor biomarker. The detection of ctDNA is helpful to evaluate tumor progression, tumor response to the therapy, and subtyping of tumor cells. Targeting next-generation sequencing (NGS) technology provides a sensitive and specific technique for ctDNA detection. It can detect multiple tumor-related gene mutations. However, collection of high quality of cell-free DNA (cfDNA) may not be available in some cases. The quality of cfDNA in plasma is impacted by multiple factors, such as plasma collection and storage conditions, DNase activity in the blood, and the apoptotic and necrotic status of the tumor. These factors affect the integrity of cfDNA, leading to full or partial degradation of cfDNA, including double-strand DNA breaks and single strand DNA nicking. Lesions on cfDNA decrease the usability of ctDNA by digital PCR and targeted NGS. Due to amount limitation of cfDNA in some cases, the repair of damaged cfDNA could be a necessary rescue step in producing viable libraries for NGS. CfDNA was extracted from the plasma with Zymo Research's Quick-cfDNA Serum and Plasma kit and was quantified by realtime PCR with Alu primer sets. The size of cfDNA was about 160 base pairs, as estimated by Agilent Tapestation 2200 with the High Sensitivity DNA kit. The DNA repair of cfDNA was conducted with PreCR Repair Mix of New England BioLabs. The sequencing library was prepared with Accel-Amplicon 56G Oncology Panel of Swift Biosciences and sequenced in Illumina's MiSeq. The quality of sequencing data was determined with FastQC. Compared to PreCR Repair Mix treated cfDNA samples, fastQ data from some of untreated cfDNA samples showed failed per base sequencing quality, about 50% of sequencing cycles with the mean quality score below 30. The per sequencing quality score of these cfDNA samples failed also to pass the quality filter. The read size distribution analysis indicated that about 60 to 70% of read sized between 30 to 45 bases and about 75 to 80% of read was smaller than 75 bases. However, sequencing data from same cfDNA samples treated with PreCR Repair Mix show a greatly improved sequencing quality. Both per base sequencing quality and per sequencing quality score passed quality filter. The above 97% of reads sized over 92 bases, complying with the requirement of 56G Oncology Panel. In conclusion, the DNA repair process before library preparation is necessary to rescue damaged cfDNA for amplicon-based NGS. Citation Format: Hong Yin, Adam H. Greer, Glenn Mills. Prior DNA repair improves the read quality in next-generation sequencing of cell-free tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3647.
Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss
Authors: Bhavna Murali, Qihao Ren, Xianmin Luo, Douglas V. Faget, Chun Wang, Radia Marie Johnson, Tina Gruosso, Kevin C. Flanagan, Yujie Fu, Kathleen Leahy, Elise Alspach, Xinming Su, Michael H. Ross, Barry Burnette, Katherine N. Weilbaecher, Morag Park, Gabriel Mbalaviele, Joseph B. Monahan, Sheila A. Stewart
Journal: Cancer Research (2018)

Abstract The role of the stromal compartment in tumor progression is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKα is frequently expressed in tumor cells and surrounding stromal cells, and its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition of p38MAPKα could reduce breast cancer metastases in a clinically relevant model. Orally administered, small-molecule inhibitors of p38MAPKα or its downstream kinase MK2 each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. This effect was primarily mediated by inhibition of the p38MAPKα pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, these inhibitors reduced tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity that drastically affects quality of life for patients with cancer. These data underscore the vital role played by stromal-derived factors in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss. Significance: Pharmacologically targeting the stromal p38MAPK-MK2 pathway limits metastatic breast cancer growth, preserves bone quality, and extends survival. Cancer Res; 78(19); 5618–30. ©2018 AACR.
In Search of a Less Invasive Approach to Cardiac Tumor Diagnosis
Authors: Teodora Donisan, Dinu Valentin Balanescu, Juan Carlos Lopez-Mattei, Peter Kim, Monika Jacquelina Leja, Jose Banchs, Konstantinos Marmagkiolis, Joerg Herrmann, Igor Gregoric, Jean-Bernard Durand, Cezar Angi Iliescu
Journal: JACC. Cardiovascular imaging (2018)
Abstract 1713: Immunomodulatory effect of statins on Tregs within human colorectal cancer is determined by the stage of disease
Authors: Belal Al-Husein
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is a public health problem worldwide and in Jordan. Statins are best seller cholesterol lowering agents. Beyond their cholesterol-lowering effects, statins use has been reported to reduce the risk of several malignances including CRC. This study aimed to assess the effect of statins on CRC risk by studying cellular infiltration of Tregs into CRC tissues and their effect on Transforming growth factor beta 1 (TGF-β1) level and angiogenesis. A total 47 specimens (25 statins users, and 22 statins nonusers) of CRC were used. Immunohistochemical analysis was performed to study Tregs infiltration by studying their specific marker fork head transcription factor (FOXP3), and angiogenesis by studying CD31 positive blood vessels. TGF-β level was measured using commercial ELISA kits. Results revealed that in case of statins use was associated with more Tregs infiltration, more angiogenesis but no difference in TGF-β1 content in tumor tissue. When further categorized analysis according to stage of disease, angiogenesis effect was more pronounced in early disease and wasn't significant in advanced disease.In addition, more Tregs infiltration was significantly noticed in advanced disease but not in early disease. Same stage-dependence wasn't notices with TGF-β1. Since statins are associated with reduced risk of death in colorectal cancer patients, we could suggest some immunologic mechanism for that. Tregs infiltration into tumor and reduction of inflammation at tumor site might reduce cancer aggressiveness in advanced disease. In advanced disease, however, reduction of angiogenesis would be the cause of tumor aggressiveness. These results suggest that statins might be used in prophylaxis or treatment of CRC. Further studies are needed to evaluate the effect of various types and doses of statins. Citation Format: Belal Al-Husein. Immunomodulatory effect of statins on Tregs within human colorectal cancer is determined by the stage of disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1713.
Advances in coamorphous drug delivery systems
Authors: Qin Shi, Sakib M. Moinuddin, Ting Cai
Journal: Acta Pharmaceutica Sinica B (2018)

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, in vitro and in vivo performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.