tbuckley/cabot-search huggingface dataset:
Methylation of Thrombospondin-4 as a potential marker of colorectal cancer
Authors: June Chia, Sarah-Jane Cozzi, Kim Loh, Catherine Bond, Kevin Spring, Barbara Leggett, Vicki Whitehall
Journal: Cancer Research (2007)

1125  BACKGROUND: Thrombospondin-4 (THBS4) is a member of the extracellular calcium-binding protein family, involved in cell adhesion and migration. The aim of this study was to evaluate deregulation of THBS4 in a series of colorectal cancers, and to examine correlations between this deregulation and molecular markers for different pathways of tumorigenesis, including microsatellite instability (MSI) and the CpG Island Methylator Phenotype (CIMP).  METHODS: Sixty-nine sporadic CRC specimens were evaluated for level of microsatellite instability (MSI) as MSI-high (MSI-H, 24), MSI-low (MSI-L, 23) or microsatellite stable (MSS, 22). Ten MSI-H CIMP negative, hereditary non-polyposis CRC (HNPCC) specimens were included for comparison. Relative levels of THBS4 gene expression, as compared to matched normal mucosa, were determined by real time RT-PCR (qRT-PCR) and analysed according to the Pfaffl method. Aberrant promoter hypermethylation was examined as a possible mechanism of gene disruption using MethyLight, with methylation being quantitated as a percentage of methylated reference (PMR).  RESULTS: THBS4 was frequently down-regulated irrespective of MSI-status in a subset of tumour samples examined for expression (5/12, 42% MSI-H; 13/17, 76% MSI-L and 9/14, 64% MSS). A trend toward more frequent THBS4 downregulation was noted in non-MSI-H cancers (P=0.09). Low level methylation was also observed in the majority of paired normal mucosa specimens, suggesting this alteration occurs very early in carcinogenesis. The average PMR observed in all normal samples was 17.7, as compared with 65.2 for tumour specimens (P  CONCLUSIONS: THBS4 is very commonly methylated and down-regulated in colorectal cancer. Based on this high frequency of gene disruption, THBS4 methylation may be a useful screening marker for early detection of CRC in non-symptomatic patients. Current studies are underway to examine THBS4 methylation normal colonic mucosa and serum samples from cancer-bearing and cancer-free patients as a possible screening tool.
Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage Commitment of Early T Cells
Authors: Gangqing Hu, Kairong Cui, Difeng Fang, Satoshi Hirose, Xun Wang, Darawalee Wangsa, Wenfei Jin, Thomas Ried, Pentao Liu, Jinfang Zhu, Ellen V. Rothenberg, Keji Zhao
Journal: Immunity (2018)
Efficacité des dilatations itératives dans la prise en charge des sténoses oesophagiennes bénignes
Authors: A Benezech, A Debourdeau, JM Gonzalez, M Barthet
Journal: Endoscopy (2018)

Les sténoses oesophagiennes bénignes récurrentes ou réfractaires (SOBR) sont fréquentes, définies par l'impossibilité d'atteindre ou de maintenir un diamètre de 14 mm après 5 procédures de dilatation endoscopique (DE). En raison du manque de recommandations, leur prise en charge reste difficile, conduisant parfois à une intervention chirurgicale radicale. L'objectif de notre étude était de déterminer l'efficacité de DE répétées et maintenues dans le temps dans la prise en charge des SOBR.
Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care
Authors: Shankar Kumar, Simon de Lusignan, Andrew McGovern, Ana Correa, Mariya Hriskova, Piers Gatenby, Simon Jones, David Goldsmith, A John Camm
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease. <h3>Design</h3> Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016. <h3>Setting</h3> The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales. <h3>Participants</h3> Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of &lt;50 mL/min/1.73m<sup>2</sup>, calculated using the chronic kidney disease epidemiology collaboration creatinine equation. Patients with a previous diagnosis of atrial fibrillation or receiving anticoagulation in the preceding 120 days were excluded, as were patients requiring dialysis and recipients of renal transplants. <h3>Intervention</h3> Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis. <h3>Main outcome measures</h3> Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality. <h3>Results</h3> 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation. <h3>Conclusion</h3> Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management.
Heparin mimetics with anticoagulant activity
Authors: Abdullah Al Nahain, Vera Ignjatovic, Paul Monagle, John Tsanaktsidis, Vito Ferro
Journal: Medicinal Research Reviews (2018)

Heparin, a sulfated polysaccharide belonging to the glycosaminoglycan family, has been widely used as an anticoagulant drug for decades and remains the most commonly used parenteral anticoagulant in adults and children. However, heparin has important clinical limitations and is derived from animal sources which pose significant safety and supply problems. The ever growing shortage of the raw material for heparin manufacturing may become a very significant issue in the future. These global limitations have prompted much research, especially following the recent well-publicized contamination scandal, into the development of alternative anticoagulants derived from non-animal and/or totally synthetic sources that mimic the structural features and properties of heparin. Such compounds, termed heparin mimetics, are also needed as anticoagulant materials for use in biomedical applications (e.g., stents, grafts, implants etc.). This review encompasses the development of heparin mimetics of various structural classes, including synthetic polymers and non-carbohydrate small molecules as well as sulfated oligo- and polysaccharides, and fondaparinux derivatives and conjugates, with a focus on developments in the past 10 years.
Les hémorragies digestives hautes liées aux anti inflammatoires non stéroidiens: aspects endoscopiques
Authors: J El Atmani, A El Farouki, S Oubaha, Z Samlani, K Krati
Journal: Endoscopy (2018)

Les lésions gastroduodénales hémorragiques provoquées par les médicaments sont souvent secondaires à la prise d'anti-inflammatoires non stéroïdiens (AINS). Cette fréquence élevée est en grande partie liée à l'automédication.
Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study
Authors: Peter C Taylor, Michael H Schiff, Qingmin Wang, Yusang Jiang, Yanli Zhuang, Regina Kurrasch, Shruti Daga, Ravi Rao, Paul P Tak, Benjamin Hsu
Journal: Annals of the Rheumatic Diseases (2018)

Objective This randomised, double-blind, parallel-group, phase 3 study compared monotherapy with sirukumab, an anti–interleukin-6 cytokine monoclonal antibody, with adalimumab monotherapy in patients with rheumatoid arthritis (RA). Methods Biologic-naïve patients with active RA who were inadequate responders or were intolerant to, or inappropriate for, methotrexate were randomised to subcutaneous sirukumab 100 mg every 2 weeks (n=187), sirukumab 50 mg every 4 weeks (n=186) or adalimumab 40 mg every 2 weeks (n=186). Primary endpoints at week 24 were change from baseline in Disease Activity Score in 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) and proportion of patients achieving an American College of Rheumatology (ACR) 50 response; these endpoints were tested in sequential order. This study is registered at EudraCT (number: 2013-001417-32) and ClinicalTrials.gov (number: NCT02019472 ). Results Significantly greater improvements from baseline in mean (SD) DAS28 (ESR) were observed at week 24 with sirukumab 100 mg every 2 weeks (−2.96 (1.580)) versus adalimumab 40 mg every 2 weeks (−2.19 (1.437); P&lt;0.001). Sirukumab 50 mg every 4 weeks also showed significantly greater improvement from baseline at week 24 in DAS28 (ESR) (−2.58 (1.524)) compared with adalimumab (P=0.013). The ACR50 response rates with the 100 mg (35.3%) and 50 mg (26.9%) doses of sirukumab were comparable to that with adalimumab (31.7%) at week 24. The safety profile of sirukumab was consistent with that observed with anti–interleukin-6 receptor antibodies. A dose-related effect on the incidence of injection-site reactions was observed with sirukumab. Conclusion Sirukumab monotherapy showed greater improvements in DAS28 (ESR), but similar ACR50 response rates, versus adalimumab monotherapy.
Definition, causes, and consequences of Hamm (idiom of distress in Arabic) in the Palestinian context: a qualitative study
Authors: Abeer A Nasir, Razan Salah, Abla Sayyed Ahmad, Samah Abu Hijleh, Sa'eed Abu Kattab, Alia Al Kurd, Rawan Al Sharif, Raed Amro, Ahmad Khatib, Hana' Mousa, Walaa Shamasnah, Khammisa Shqerat, Rita Giacaman
Journal: The Lancet (2018)
Le siège des polypes coliques influence-t-il leur taux de détection à la coloscopie?
Authors: K Agar, L Hamzaoui, M Medhioub, K Amal, MM Azouz
Journal: Endoscopy (2018)

La coloscopie est l'examen de référence pour la détection et traitement des polypes coliques, réduisant ainsi l'incidence des cancers colorectaux. Mais une coloscopie n'est jamais parfaite et peut manquer quelques polypes à cause de facteurs modifiables comme une mauvaise préparation, un retrait trop rapide du coloscope, et non modifiables comme une très petite taille du polype ou son siège rendant nécessaire le changement de la position lors de la coloscopie selon quelques études.
Public will have to pay £220bn for PFI until 2040, NAO calculates
Authors: Adrian O’Dowd
Journal: BMJ (2018)

The UK’s main public spending watchdog has calculated that the public will have to pay almost £200bn for private finance initiative (PFI) schemes until the 2040s.

A new National Audit Office report looks at PFI contracts in all sectors and PF2, the successor introduced during David Cameron’s premiership as an improved form of public-private financing deals.1 The NAO calculated that even if no new deals were entered into, future charges, which will continue into the 2040s, amounted to £199bn (€225bn; £275bn).

Because of the extra costs attached to PFI schemes—such as a higher cost of finance, insurance, fees for external advisers, and the cost of producing and auditing accounts—overall cash spending on PFI and PF2 projects was higher than …
Abstract 13332: Ventricular Arrhythmias in Patients With Continuous-flow Left Ventricular Assist Devices
Authors: David Kuten, Rhondalyn McLean, Stuart Russell
Journal: Circulation (2013)

Introduction:  Ventricular arrhythmias (VAs) pose a significant burden in patients with continuous flow left ventricular assist devices (cfLVADs). However, the incidence, risk factors, and impact on survival are not yet well-described.   Hypothesis:  We hypothesized that there were demographic, hemodynamic, and comorbid condition parameters that would predict post-VAD arrhythmias and mortality.   Methods:  We performed a retrospective analysis of 106 consecutive patients undergoing placement of cfLVADs between April 2007 and September 2012. Exploring the outcomes of early VA (occurring during the index hospitalization), late VA (occurring after discharge) and death, we compared demographic, comorbid, pharmacologic, and clinical data. Time to event analyses were undertaken to identify predictors of the outcomes.   Results:  Most subjects were men (73%) with non-ischemic heart failure (70%) and an ICD (92%) in place. Forty six (43%) patients died. Pre-LVAD VA (hazard ratio [HR] 5.99, p=0.048), chronic kidney disease (HR 2.09, p=0.025) and diabetes (HR 3.61, p   Conclusions:  Ventricular arrhythmias following LVAD placement are common and predicted by pre-LVAD arrhythmia and ICD therapy, comorbid conditions and medication use. For the rare patient without an ICD placed pre-LVAD, post-operative implantation should be considered.
UV irradiation-induces DNA hypermethylation and that leads to the transcriptional silencing of the tumor suppressor genes in UV-exposed skin and tumors
Authors: Vijayalakshmi Nandakumar, Syed Meeran, Trygve Tollefsbol, Santosh Katiyar
Journal: Cancer Research (2008)

2535  Epigenetics, the heritable processes that modulate gene activity without changes in the DNA sequence, have gained considerable recent interest especially in the areas of cell cycle control, DNA damage and repair, angiogenesis, cancer and aging. Cancer epigenetics is an emerging field dealing with important processes like DNA methylation and histone modification patterns that can either activate oncogenes or inactivate tumor suppressor genes, the crucial steps in tumor development. Exposure of skin to solar ultraviolet (UV) radiation induces DNA damage and inflammation, which contribute to development of melanoma and nonmelanoma skin cancers. Since CpG islands acquire abnormal methylation at the 5’regulatory region of genes in most of the diseases, we sought to determine the global DNA methylation pattern in the UV-exposed skin and tumors. For this purpose SKH-1 hairless mice were subjected to photocarcinogenesis protocol. When tumor yield was stabilized, mice were sacrificed and skin and tumor samples collected for the analysis. The status of DNA methylation patterns were determined by immunostaining using a monoclonal antibody specific to 5-methylcytosine and by a quantitative assay to measure the global DNA methylation levels. Hypermethylation pattern of DNA was found in UV-exposed skin compared to non-UV-exposed skin. The expression levels of the various DNA methyltransferases, e.g., Dnmt1, Dnmt3a and Dnmt3b, were found to be 2-4- folds higher in UV-exposed skin than non-UV-exposed controls, as analyzed by immunostaining and real-time PCR. The overall activity of Dnmts was higher by ~50% in the UV-exposed skin compared with the normal skin. Similar pattern of DNA methylation was also observed in UV-induced skin tumors; however the levels of DNA hypermethylation were greater in tumors than UV-exposed skin. The hypermethylation of DNA in UV-exposed skin and tumors may lead to silencing of tumor suppressor genes, thereby contributing to the risk of skin cancer. We also have analyzed the methylation status of the various tumor suppressor genes, like P16INK4a, RASSF1A and CDH1, on UVB exposure through methylation specific PCR and the relative repression levels of their mRNA using real-time PCR, which indicated that the levels of these tumor suppressor genes were downregulated in UV-exposed skin and tumors on hypermethylation. The increased expression of the MeCP2, a methyl binding protein, and histone deacetylase 1 (HDAC 1), in UV-exposed skin shows that the aberrant hypermethylation of DNA recruited the HDAC 1 to the methylated CpGs through MeCP2 which had caused the repressive effect of the genes either by their direct association with DNA or by complexing with HDAC 1. These data suggest in detail for the first time that UV-induced hypermethylation in DNA may have a role in UV-induced skin cancer development.
Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance)
Authors: Temidayo Fadelu, Sui Zhang, Donna Niedzwiecki, Xing Ye, Leonard B. Saltz, Robert J. Mayer, Rex B. Mowat, Renaud Whittom, Alexander Hantel, Al B. Benson, Daniel M. Atienza, Michael Messino, Hedy L. Kindler, Alan Venook, Shuji Ogino, Kimmie Ng, Kana Wu, Walter Willett, Edward Giovannucci, Jeffrey Meyerhardt, Ying Bao, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2018)

Purpose Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia, including type 2 diabetes, obesity, sedentary lifestyle, and high glycemic load diet. Nut intake has been associated with a lower risk of type 2 diabetes, metabolic syndrome, and insulin resistance. However, the effect of nut intake on colon cancer recurrence and survival is not known. Patients and Methods We conducted a prospective, observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency questionnaires while enrolled onto a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. Results After a median follow-up of 6.5 years, compared with patients who abstained from nuts, individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio (HR) for disease-free survival of 0.58 (95% CI, 0.37 to 0.92; P trend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; P trend = .01). In subgroup analysis, the apparent benefit was confined to tree nut intake (HR for disease-free survival, 0.54; 95% CI, 0.34 to 0.85; P trend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; P trend = .04). The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality. Conclusion Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer.
P1.03-050 Outcomes after the Decision to Biopsy: Results from a Nurse Practitioner Run Multidisciplinary Lung Cancer Screening Program
Authors: Christopher Gilbert, Joelle Fathi, Candice Wilshire, Brian Louie, Ralph Aye, Alexander Farivar, Eric Vallieres, Jed Gorden
Journal: Journal of Thoracic Oncology (2017)
Abstract 18745: Outcomes of Mechanical Circulatory Support for Patients With Functionally Single-Ventricle Physiology at Different Stages of Surgical Palliation
Authors: Arezou Saedi, Devin Chetan, Yasuhiro Kotani, Nishanthi Liyanage, Lisa Zhao, Christopher Caldarone, Glen Van Arsdell, Osami Honjo
Journal: Circulation (2013)

Introduction: Mechanical circulatory support (MCS) for functionally single ventricle (SV) physiology poses significant challenges. We sought to analyze the results of MCS at 4 different stages of the surgical palliation process. Methods: From 2003 to 2013, 86 SV patients required MCS: Group 1, before any surgical palliation (n=13, 15%), Group 2, between stage I and II (n=59, 69%), Group 3, between stage II and Fontan (n=10, 12%), Group 4, after Fontan (n=4, 5%). Indications for MCS included failure to wean from cardiopulmonary bypass in 6 (7%) patients, circulatory failure in 7 (8%), respiratory failure in 9 (10%), cardiopulmonary failure in 4 (5%), and cardiac arrest in 58 (67%). Kaplan-Meier analysis was used to compare freedom from death and freedom from failure to wean between groups. Cox analysis was used to determine risk factors. Results: The median MCS duration was 3 days (IQR, 1-6). Of 86 patients, 58 (67%) were successfully weaned: 32 (37%) patients recovered, 8 (9%) were transplanted, 12 (14%) had operation/reoperation, and 1 (1%) had conversion to a different form of MCS. Fifty-two (60%) patients had complications including bleeding in 20, thromboembolism in 9, sepsis in 12, neurologic injury in 6, and multi-organ failure in 5. Thirteen patients required a second run of MCS. Freedom from death at 6 months after MCS initiation was comparable between the groups (Group 1, 23%, Group 2, 33%, Group 3, 15%, Group 4, 50%, p=0.66; Figure 1). Failure to wean from MCS was also comparable among the groups (p=0.46). Cox analysis revealed MCS-related complications as a risk factor for death (p=0.006) and longer duration of arrest as a risk factor for inability to wean from ECMO (p=0.036). The timing of MCS was not a risk factor for poor outcomes. Conclusions: Two thirds of SV patients who required MCS were rescued, although subsequent survival is generally poor across all stages of palliation. Given the poor outcomes in this cohort, consideration of alternative strategies is warranted.
A novel antitumor effect of water extract from Pleurotus cornucopia that promotes dendritic cell activation and down-regulation of regulatory T cells in tumor-bearing mice
Authors: Kazunori Kato, Shinobu Kaihou, Shin-Ya Hagiwara, Takahiro Tomiyama, Hirofumi Hamada
Journal: Cancer Research (2005)

730  The fruit body of the mushroom Pleurotus cornucopiae (Tamogitake) has traditionally been used as a health food for the prevention of hypertension, diabetes and cancer. In the present study, we examined for the antitumor activity of the extract of Pleurotus cornucopiae using a sarcoma 180 (S180) transplantation experimental model mice and its immune adjuvant mechanism on dendritic cells (DC) and regulatory T cells (T-reg). ICR mice were transplanted intramuscular injection with S180 (5 million cells/mouse) followed by oral administration of hot water extract of Pleurotus cornucopiae at a dose of 1.3 or 4.0 ml/kg/day for 35 days. The administration of Pleurotus cornucopiae resulted in significant inhibition of S180 tumor growth and prolonged the survival compared with saline-administrated tumor-bearing mice. In order to clarify the antitumor mechanism of Pleurotus cornucopiae, we investigated the immuno-modulatory effect on the activation of DC in vitro. In contrast to immature DC, treatment of DC with Pleurotus cornucopiae extract expressed high levels of costimulatory molecules (i.e., CD54 and CD86), and activation/maturation markers (i.e., CD25 and CD83). Interleukin 12 (IL-12) is produced in large amounts by mature, not by immature, DC and therefore is a suitable factor to determine DC maturation. DC stimulated with Pleurotus cornucopiae extract could produce significantly higher levels of IL-12 in a dose-dependent manner than those stimulated without or with Agaricus blazei. We also found the active substances to induce DC activation and aggregation in molecular weight of under 3-kDa fractions isolated by ion exchange chromatography and gel chromatography. These findings suggested that culturing with Pleurotus cornucopiae extract that might contain lectin-like molecules could efficiently generate functionally mature DC. We next investigated the possibility that T-reg populations may be responsible for the antitumor effect of Pleurotus cornucopiae. Consistent with antitumor effect, tumor-bearing mice administrated with the extract of Pleurotus cornucopiae have significantly decreased numbers of CD4+CD25+ T-reg population in spleen (16.2 ± 0.6%) compared with saline-treated tumor bearing mice (24.7 ± 3.8%). Collectively, these findings indicate that Pleurotus cornucopiae contains active substances that display its ability to enhance antitumor immunity mediated by DC and T-reg.