tbuckley/cabot-search huggingface dataset:
A1.20 Epigenetic modificationsand TLR8 signalling contribute to systemic sclerosis pathogenesis by ros and profibrotic genes induction
Authors: M Ciechomska, P Zarecki, D Piatek, M Merdas, J Swierkot, E Morgiel, JM van Laar, W Maslinski, K Bogunia-Kubik
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease characterised by skin and &nbsp;internal organs fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from SSc patients play a role in SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction, which contribute to fibrosis progression and chronic inflammation. The exact factors driving TIMP-1, IL-8 and ROS secretion are still unknown. The aim of this study was to investigate the expression pattern of profibrotic IL-8, TIMP-1, AP1 transcription factor-Fra2 and ROS induction in peripheral blood monocytes following DZNep (histone methyltransferase inhibitor) and TLR8 agonist (ssRNA) stimulation. <h3>Materials and methods</h3> The expression of Fra2, IL-8 and TIMP-1 and anti-oxidant superoxide dismutase 1 (SOD1) was measured by qRT-PCR in stimulated and unstimulated HC (n = 14) and SSc (n = 17) monocytes. Generation of ROS was determined using luciferase based assay. Fra2 DNA-binding activity was measured in AP-1 transcription assay in monocytic U937 cell line following epigenetic and TLR8 modifications. The level of anti-fibrotic miRNA-5196, which is predicted to bind and inhibit 3'UTR of Fra-2 gene, was also determined in HC and SSc monocytes. <h3>Results</h3> Combination of DZNep+TLR8 enhanced Fra2 (2-fold, p = 0.02), TIMP-1 (2-fold) and IL-8 (7.87-fold, p &lt; 0.001) expression in SSc monocytes. Fra2 DNA-binding activity was 1.5-fold increased upon stimulation. Secreted level of TIMP-1 was 1.46-fold higher in SSc monocytes compared to unstimulated cells. Generated ROS was 2.21-fold (p = 0.0395) higher following DZNep+TLR8 stimulation in monocytic U937 cells. In contrast, miRNA-5196 expression was&nbsp;2.13-fold decreased in SSc monocytes upon DZNep+TLR8 stimulation. Also the level of SOD1 was decreased in HC and SSc monocytes following stimulation, 2.16-fold (p = 0.025) and 1.56-fold, respectively. <h3>Conclusions</h3> These data suggest that DZNep and TLR8 agonist are able to enhance pro-fibrotic TIMP-1, IL-8 and oxidative stress generation. As opposed by the decrease of anti-fibrotic miRNA-5196 and anti-oxidant SOD1 expression in SSc monocytes, which might be used as a potential modulators of fibrogenesis in SSc. Supported by Homing Plus grant/2013–8/4 from Foundation for Polish Science and UMO-2015/16/S/NZ6/00041 from National Science Centre, Poland.
Politics and Universal Health Coverage
Authors: P Dileep Kumar
Journal: New England Journal of Medicine (2016)

To the Editor: In the map in the Perspective article by Gupta et al. (Sept. 24 issue),1 the six member states of the Cooperation Council for the Arab States of the Gulf (CCASG) — Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates — should have been shaded. All these countries provide universal health coverage to their citizens. The dynamics in these oil-rich countries are different from those in other countries that the authors describe. The governments and citizens of the CCASG member states expect universal coverage because of the strength of their economies. However, the cost of . . .
Abstract 684: Novel potent curcumin analogues EF-31 and UBS109 inhibit DNA methylation and induce SPARC expression in pancreatic cancer.
Authors: Purnachandra Nagaraju Ganji, Shijun Zhu, Shoji Mamoru, Bassel El-Rayes
Journal: Cancer Research (2013)

Abstract Purpose/Objectives: DNA methylation is an essential step in epigenetic modification and carcinogenesis. HSP90 and NF-κB have a central role in DNA methylation. Curcumin down regulates HSP90 and NF-kB. UBS109 and EF-31 are potent synthetic analogues of curcumin. We tested the hypothesis that EF-31 and UBS-109 can inhibit DNA methylation and induce SPARC through inhibition of NF-kB and HSP90 in pancreatic cancer cell lines. Methods: Two pancreatic cancer cell lines were used, PANC-1 and Mia-PaCa2. Cells were either untreated (control) or treated with curcumin (20μM), EF-31 (750nM) and UBS-109 (250nM) for 24 hours. Western blot and RT-PCR analyses were carried out to determine the effect of curcumin and its analogues EF-31 and UBS-109 on different signal molecules involved in carcinogenesis. Electromobility shift assay (EMSA) was performed in pancreatic cells to evaluate the effects of ganetespib on NF-kB activity. Immunocyto and histo chemistry assays were also performed. Results: The treatment of pancreatic cancer cell lines with curcumin and its analog EF-31 and UBS-109 inhibited NF-κB and HSP90 at transcriptional and translational level resulting in inhibition of DNMT1, decrease in CpG island methylation and up-regulation of SPARC. EF-31 and UBS109 were more potent at inhibition of DNMT1 than curcumin. To confirm that the observed effects were mediated by NF-kB, a stable transfection with p65 (NF-kB) was performed. Cells with overexpression of NF-κB resulted in increased DNMT-1, HSP90 protein and decreased SPARC. Inhibition of NF-kB using EF31 or UBS109 resulted in up-regulation of SPARC and inhibition of the DNMT due to NF-κB down-regulation. Similar effects were observed in tumors from animals treated with EF-31 and UBS-109. Conclusion: UBS109, EF31 and curcumin can inhibit DNA methylation through down-regulation of DNMT-1 expression by NF-kB. Inhibition of methylation was associated with expression of silenced genes such as SPARC. UBS109 and EF31 are significantly more potent than curcumin. UBS109 and EF31 are promising agents for therapy in pancreatic cancer. Citation Format: Purnachandra Nagaraju Ganji, Shijun Zhu, Shoji Mamoru, Bassel El-Rayes. Novel potent curcumin analogues EF-31 and UBS109 inhibit DNA methylation and induce SPARC expression in pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 684. doi:10.1158/1538-7445.AM2013-684
Colonic mucosa-associated lymphoid tissue (MALT) lymphoma: an important differential diagnosis for a slow-growing colonic polyp
Authors: Rohit Anand, Shashank Garg, Ethan Dubin, Sudhir Dutta
Journal: Endoscopy (2014)

A 67-year-old man came to the gastroenterology clinic in 2013 for follow-up of a slow-growing asymptomatic colonic polyp. The polyp was first found on screening colonoscopy in 2006. It was smooth, sessile, 2 cm in size, and located in the transverse colon ([Fig. 1]). Histopathology results from the biopsy showed dense infiltrates of CD20 + lymphocytes within the lamina propria and a diagnosis of low grade extranodal mucosa-associated lymphoid tissue (MALT) lymphoma was made. The abdominal positron emission tomography-computed tomography (PET-CT) scan was unremarkable. Helicobacter pylori IgG antibody testing was equivocal and a 2-week course of ampicillin, clarithromycin, and esomeprazole was administered. Surveillance colonoscopy in 2007 showed the MALToma to be 3 cm in size. Because of its growing size, the patient was treated with four cycles of rituximab. Follow-up colonoscopy in 2010 showed that the mass had grown to 4 cm in size. A repeat PET-CT scan in 2012 was unremarkable. Colonoscopy in 2013 showed the mass to be 5 cm in size with blood oozing from the surface ([Fig. 2]). A repeat biopsy showed diffuse infiltration of the mucosa with lymphoid cells positive for CD20, CD79a and bcl2. Because of the increasing size and mucosal friability, laparoscopic colonic resection was performed. The colonic margins were clear and three lymph nodes were involved. The pathology report confirmed the diagnosis of extranodal MALT lymphoma (stage 1E).
Control of luminal type A intrinsic subtype enriched transcription factor network by insulin: implications of diabetes on breast cancer classification.
Authors: KR McCune, P Bhat-Nakshatri, M Thorat, S Badve, H Nakshatri
Journal: Cancer Research (2009)

Abstract Abstract #3029 Background: Luminal type A and type B represent estrogen receptor alpha (ERalpha)-positive breast cancers with luminal type A expressing higher levels of ERalpha and is associated with better prognosis. Recent studies have identified a specific functional transcription factor network comprising GATA-3, FOXA1 and ERalpha in normal luminal cells as well as in luminal type A breast cancer that dictates their hormone dependence. Signaling molecules that may disrupt this network and force these cells to acquire hormone-independence are not known. T-bet (Tbx21) has been described as a major negative regulator of GATA-3 activity. As the expression and/or activity of some of the above factors are controlled by insulin, the objective of this study was to investigate whether elevated level of insulin, as evidenced in type II diabetes, alters gene expression pattern in luminal type A breast cancers by interrupting GATA-3:FOXA1:ERalpha network and thus forcing these cancers to acquire non-luminal phenotype and/or hormone-independence.&amp;#x2028; Methodologies: The effect of insulin on the expression of ERalpha, FOXA1, GATA-3 and T-bet was measured in ERalpha-positive MCF-7 cells by Western blot analysis. The effect of T-bet on estrogen-regulated gene expression was measured by stable overexpression of T-bet in MCF-7 cells and subsequent qRT-PCR analysis. Publicly available Oncomine database was used to determine the expression pattern of T-bet and its relation to ERalpha status in primary breast cancers. A proliferation assay was used to determine sensitivity of T-bet overexpressing cells to tamoxifen in the presence and absence of insulin.&amp;#x2028; Results: Insulin induced the expression of T-bet, which was partially reversed by estrogen. ERalpha and GATA-3 levels were reduced in MCF-7 cells stably overexpressing T-bet suggesting that T-bet reduces GATA-3-dependent ERalpha expression. Estrogen-inducible expression of estrogen target genes GREB-1 and Myb was lower in T-bet overexpressing cells compared to parental cells, although basal expression was elevated in T-bet overexpressing cells. Treatment of T-bet overexpressing cells with insulin decreased tamoxifen sensitivity. Although T-bet expression was generally higher in ERalpha-negative breast cancers compared to ERalpha-positive breast cancers, a subpopulation of ER-positive breast cancers express elevated levels of T-bet.&amp;#x2028; Conclusions: Insulin may change the gene expression pattern through T-bet-mediated disruption of master cell-type-specific transcriptional network including GATA-3, ERalpha and FOXA1 that dictates the phenotype of hormone-dependent luminal type A breast cancer. T-bet may serve as a marker to identify ERalpha-positive breast cancers that express low levels of GATA-3 and have progressed to hormone-independence. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3029.
Abstract 4853: Constitutively decreased TGF-β signaling and risk for colorectal cancer
Authors: Michael J. Pennison, Naresh Bellam, Jacquelyn Zimmerman, Qinghua Zeng, Maureen Sadim, Virginia Kaklamani, Nengjun Li, Kui Zhang, Daniel O. Stram, Boris Pasche
Journal: Cancer Research (2012)

Abstract Background: Approximately one third of all colorectal cancers (CRC) are inherited, but less than 7% are attributable to known gene mutations. Germline variants within the TGF-β signaling pathway may account for colorectal cancer risk since TGF-β inhibits early tumor development through the activation of SMAD proteins. We have previously shown that Tgfbr1 haploinsufficiency is a potent modifier of colorectal cancer development in mice and humans. We have recently shown a significant association between a 3 SNP TGFBR1 haplotype and constitutively decreased TGFBR1 allelic expression, a phenotype found to occur frequently in patients with CRC. In this family-based study, we aimed at determining the association of TGFBR1 and SMAD7 with colorectal cancer risk. Methods: We studied 1,558 colorectal cancer cases and 2,640 healthy controls recruited by the Colorectal Cancer Family Registry (CCFR). We genotyped 14 TGFBR1 haplotype tagging SNPs as well as a SMAD7 SNP associated with CRC in prior GWA studies. SNPs were genotyped in all cases and controls using ABI's TaqMan platform, and associations were determined using logistical regression analysis (significance set at p&amp;lt;0.05). Main effects (Cockerham model) and risk prediction accuracy (receiver operating characteristic curves) were also determined. Functional assessment was conducted with derived lymphoblastoid cell lines (LCLs). Results: TGFBR1 rs7034462 and SMAD7 rs4939827 were strongly associated with colorectal cancer risk (see Table). Functional assessment performed with 3 matched pairs of patient-derived LCLs showed significantly reduced TGF-β mediated SMAD signaling in cells carrying these two SNPs. Conclusions: Our study provides the first evidence that a combination of TGFBR1 and SMAD7 variants is associated with constitutively decreased TGF-β signaling and risk for colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4853. doi:1538-7445.AM2012-4853
PTU-001 Propanolol at modest dose does not impair survival in patients with cirrhosis and refractory ascites: Abstract PTU-001 Figure 1
Authors: A E Robins, A Bowden, W Watson, F Smith, W T Gelson, W J Griffiths
Journal: Gut (2012)

<h3>Introduction</h3> A recent study suggesting β-blockers should be contra-indicated in cirrhotic patients with refractory ascites has gained significant attention.<sup>1</sup> We sought to examine this hypothesis in a cohort of patients undergoing elective paracentesis in a tertiary liver unit. <h3>Methods</h3> We retrospectively studied 114 consecutive patients undergoing regular paracentesis between July 2007 and December 2010 at Addenbrooke9s Hospital. 36 patients were maintained on propanolol for variceal prophylaxis, whereas 78 were not β-blocked. Mortality and morbidity were compared between the two groups. The χ<sup>2</sup>, Mann–Whitney and Kaplan–Meier methods were employed for statistical analysis. <h3>Results</h3> There was no statistically significant difference between the two groups in terms of age, sex, aetiology of liver disease (predominantly alcohol), Child-Pugh score and UKELD. Hepatocellular carcinoma was present in 16% of patients in the propanolol group and 13% of the non β-blocked group (p=0.62). Varices were predictably present more in the propanolol group compared with the non β-blocked group (97% vs 59%, p&lt;0.001). The mean total daily dose of propanolol used was 48.9 mg. The incidence of spontaneous bacterial peritonitis was similar between the propanolol group and non β-blocked group (43% vs 50%, p=0.51). The incidence of overt encephalopathy was also no different (43% vs 44%, p=0.93). Variceal bleeding occurred more frequently in the propanolol group compared with the non β-blocked group (69% vs 41%, p&lt;0.01). Median survival was 18 months in the propranolol group vs 11 months in the non-propanolol group, with no significant difference between Kaplan–Meier survival curves (p=0.93, log rank test) (Abstract PTU-001 figure 1). <h3>Conclusion</h3> This study demonstrates that propanolol used in a total daily dose of between 40 and 80 mg is safe in patients with cirrhosis and refractory ascites. Deleterious effects at higher doses cannot be excluded. Notwithstanding this limitation and the retrospective nature of the analysis, these data reassure regarding the use of β-blockers in this patient group and that such drugs should not be immediately contraindicated. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Serste T</b>, Melot C, Francoz C, <i>et al</i>. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. <i>Hepatology</i> 2010;<b>52</b>:1017–22.
Hypertrophic Osteoarthropathy Seen With NaF18 PET/CT Bone Imaging
Authors: Carina Mari Aparici, Sukhkarn Bains
Journal: Clinical Nuclear Medicine (2011)

Bone scintigraphy with technetium-labeled agents is effective in demonstrating hypertrophic osteoarthropathy. The findings have been described as the “tram-line” or “double-stripe” sign. NaF18 PET/CT scan provides improved image quality compared with technetium scintigraphy. In this study, a 52-year-old woman with lung cancer and bone pain had a NaF18 PET/CT examination that clearly demonstrated the detailed findings of hypertrophic osteoarthropathy.
Latent Rheumatic Myocarditis
Authors: Joseph Rogers, Stanley L. Robbins
Journal: New England Journal of Medicine (1947)

RHEUMATIC fever, a systemic disease affecting chiefly the heart, has always been considered to be primarily a disorder of childhood with a markedly diminished incidence of initial and recurrent attacks after puberty.1 , 2 At the younger age levels rheumatic fever follows a variable but usually recognizable pattern, with carditis, arthralgia, chorea and subcutaneous nodules as major manifestations and with fever, abdominal pains, skin rashes, epistaxis and changes in the electrocardiogram, sedimentation rate and white-cell count as minor manifestations of the disease.3 It is also appreciated, however, that all these features may be absent in any individual case and that characteristic signs . . .
Bone Scan in Strenuous Abdominal Muscular Exercise
Authors: DANIEL S. RIMKUS, GEETHA ASHOK, MARK H. JAMALI
Journal: Clinical Nuclear Medicine (1996)

A 15-year-old boy was referred for bone scanning to evaluate a possible stress fracture in the left tibia and femur. Intense activity in the abdomen and pelvis was incidentally noted, which on lateral views was confirmed to be in the anterior abdominal muscles. The patient did not have any abdominal pain at the time of the scan, but did report a history of extreme muscular soreness after intense abdominal exercise 3 weeks before the scan.
Acute Cholecystitis in the Postoperative Period
Authors: Ronald J. Knudson, William F. Zuber
Journal: New England Journal of Medicine (1963)

TRANSIENT fever, pain, ileus and general discomfort are so common after any surgical procedure that development of a new surgical emergency is often masked by these almost routine sequelae. The natural reluctance of the medical mind to seek a second diagnosis when one is obvious may lead the physician into dangerous complacency in the presence of a new disease occurring in the immediate postoperative period. Fortunately, increasing awareness of this problem has led to prompt diagnosis and treatment of such emergencies. Acute cholecystitis after unrelated surgical procedures constitutes such an emergency. A desire to elucidate the features of this problem . . .
METABOLIC SYNDROME AND THE RISK OF ADVERSE CARDIOVASCULAR EVENTS AFTER AN ACUTE CORONARY SYNDROME: INSIGHTS FROM SOLID-TIMI 52 TRIAL
Authors: Ilaria Cavallari, Christopher Cannon, Eugene Braunwald, Erica Goodrich, Kyungah Im, Mary Ann Lukas, Michelle O'Donoghue
Journal: Journal of the American College of Cardiology (2016)
CLINICAL PREDICTORS FOR INAPPROPRIATE INITIAL DIAGNOSIS OF ACUTE TYPE A AORTIC DISSECTION IN THE EMERGENCY ROOM
Authors: Kazuhito Hirata, Minoru Wake, Takanori Takahashi, Jun Nakazato, Nobuhito Yagi, Tadayoshi Miyagi, Junichi Shimotakahara, Tsuyoshi Takara, Toshiho Tengan
Journal: Journal of the American College of Cardiology (2015)
THE PROGNOSTIC SIGNIFICANCE OF ELECTROCARDIOGRAPHIC PARAMETERS FOR NEW ONSET HEART FAILURE IN THE GENERAL POPULATION
Authors: Niek Verweij, Frank P. Brouwers, Rudolf A. De Boer, Hans J. Hillege, Dirk J. van Veldhuisen, Wiek H. van Gilst, Pim van der Harst
Journal: Journal of the American College of Cardiology (2015)
Autologous hematopoietic stem cell transplantation as salvage treatment for advanced B cell chronic lymphocytic leukemia
Authors: L Sutton, K Maloum, H Gonzalez, H Zouabi, N Azar, C Boccaccio, F Charlotte, J-M Cosset, J Gabarre, V Leblond, H Merle-Beral, J-L Binet
Journal: Leukemia (1998)
Cessation of Therapy during Complete Remission of Childhood Acute Lymphocytic Leukemia
Authors: Rhomes Joao Amin Aur, Joseph V. Simone, H. Omar Hustu, Manuel S. Verzosa, Donald Pinkel
Journal: New England Journal of Medicine (1974)

Abstract To assess the need for prolonged therapy in acute lymphocytic leukemia in remission, we studied the course of 132 patients removed from therapy after two to three years of remission. The median period off therapy was 21 months, with a range of one month to 7.5 years. Of the patients removed from therapy, 21 have relapsed (16 per cent). Of the patients who relapsed, six had not received specific Central-nervous-system therapy. We conclude that (1) programs for treatment of childhood acute lymphocytic leukemia have resulted in an impressive number of long-term leukemia-free survivals even after cessation of all therapy, (2) the likelihood of relapse after therapy is stopped is greatest in the first year, (3) relapse was more frequent in patients who had not received Central-nervous-system irradiation, and (4) no other feature was found to predict whether relapse would occur after stopping therapy. (N Engl J Med 291:1230–1234, 1974)
David Oliver: The best health system
Authors: David Oliver
Journal: BMJ (2016)

Future funding and delivery of UK health services is the subject of unprecedented debate. The media are filled with opinionated talking heads citing selective evidence comparing nations.

Ranking systems isn’t easy. Health outcomes are influenced by socioeconomic and lifestyle determinants. Ratings depend on the items picked, the weight given, and the ideological frame. The United Kingdom has four national systems, although they are often unhelpfully aggregated.

Spending per capita or as a percentage of gross domestic product (GDP) is easier to rank than performance. The Organisation for Economic Cooperation and Development (OECD) and the Economist …