tbuckley/cabot-search huggingface dataset:
The Impact of Autoimmune Hepatitis and Its Treatment on Health Utility
Authors: Lin Lee Wong, Holly F Fisher, Deborah D Stocken, Stephen Rice, Amardeep Khanna, Michael A Heneghan, Ye Htun Oo, George Mells, Stuart Kendrick, Jessica Katharine Dyson, David E. J. Jones
Journal: Hepatology (2018)

Patient reporting suggests that the physical and psychological effects of autoimmune hepatitis (AIH) can be substantial. However, health‐related quality of life (HRQOL) in patients with AIH remains incompletely characterized, and health utility remains to be explored. Treatment for AIH often includes the use of corticosteroids, which are agents that can be associated with significant adverse effects. Here we explore the impact of AIH and its treatments on patient‐reported HRQOL and health utility in a large cohort of prevalent cases from the United Kingdom Autoimmune Hepatitis (UK‐AIH) national study. Data were collected from 990 adult participants with a clinical diagnosis of AIH using validated HRQOL tools including the European Quality‐of‐Life 5‐Dimension 5‐Level (EQ‐5D‐5L) and clinical data forms. The EQ‐5D‐5L dimension scores were compared with UK population norms and with a disease control cohort with primary biliary cholangitis (PBC). Within the AIH cohort, regression analysis was used to explore associations between HRQOL and demographic and clinical variables with a particular focus on the impact of AIH therapies including corticosteroid use. HRQOL, measured by the EQ‐5D‐5L utility index, is shown to be significantly impaired in our cohort of AIH patients compared with population norms. Within the AIH cohort, corticosteroid use was found to be significantly associated with impaired HRQOL, even when controlling for biochemical disease activity status. Conclusion: Our data show evidence of HRQOL impairment in a large cohort of AIH patients compared with the general population. Furthermore, corticosteroid use is strongly associated with decreased HRQOL, independent of remission status. This highlights the need for better corticosteroid‐free therapy approaches and it emphasizes the need for future novel therapeutic trials in AIH. (H epatology 2018; 00:000‐000).
Identification of Smoking-Associated Differentially Methylated Regions Using Reduced Representation Bisulfite Sequencing and Cell type–Specific Enhancer Activation and Gene Expression
Authors: Ma Wan, Brian D. Bennett, Gary S. Pittman, Michelle R. Campbell, Lindsay M. Reynolds, Devin K. Porter, Christopher L. Crowl, Xuting Wang, Dan Su, Neal A. Englert, Isabel J. Thompson, Yongmei Liu, Douglas A. Bell
Journal: Environmental Health Perspectives (2018)

Background: Cigarette smoke is a causal factor in cancers and cardiovascular disease. Smoking-associated differentially methylated regions (SM-DMRs) have been observed in disease studies, but the causal link between altered DNA methylation and transcriptional change is obscure. Objective: Our objectives were to finely resolve SM-DMRs and to interrogate the mechanistic link between SM-DMRs and altered transcription of enhancer noncoding RNA (eRNA) and mRNA in human circulating monocytes. Method: We integrated SM-DMRs identified by reduced representation bisulfite sequencing (RRBS) of circulating CD14+ monocyte DNA collected from two independent human studies [n=38 from Clinical Research Unit (CRU) and n=55 from the Multi-Ethnic Study of Atherosclerosis (MESA), about half of whom were active smokers] with gene expression for protein-coding genes and noncoding RNAs measured by RT-PCR or RNA sequencing. Candidate SM-DMRs were compared with RRBS of purified CD4+ T cells, CD8+ T cells, CD15+ granulocytes, CD19+ B cells, and CD56+ NK cells (n=19 females, CRU). DMRs were validated using pyrosequencing or bisulfite amplicon sequencing in up to 85 CRU volunteers, who also provided saliva DNA. Results: RRBS identified monocyte SM-DMRs frequently located in putative gene regulatory regions. The most significant monocyte DMR occurred at a poised enhancer in the aryl-hydrocarbon receptor repressor gene (AHRR) and it was also detected in both granulocytes and saliva DNA. To our knowledge, we identify for the first time that SM-DMRs in or near AHRR, C5orf55-EXOC-AS, and SASH1 were associated with increased noncoding eRNA as well as mRNA in monocytes. Functionally, the AHRR SM-DMR appeared to up-regulate AHRR mRNA through activating the AHRR enhancer, as suggested by increased eRNA in the monocytes, but not granulocytes, from smokers compared with nonsmokers. Conclusions: Our findings suggest that AHRR SM-DMR up-regulates AHRR mRNA in a monocyte-specific manner by activating the AHRR enhancer. Cell type–specific activation of enhancers at SM-DMRs may represent a mechanism driving smoking-related disease. https://doi.org/10.1289/EHP2395
Life in vaccine science – a conversation with Stanley Plotkin at the 4th Conference on Vaccines in Dubrovnik, Croatia, September 2017
Authors: Sanjin Musa
Journal: Eurosurveillance (2018)

Preview this article: Life in vaccine science – a conversation with Stanley Plotkin at the 4th Conference on Vaccines in Dubrovnik, Croatia, September 2017, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/23/17/eurosurv-23-17-6-1.gif
Abstract 19834: MicroRNA-148a Inhibits Expression of Plasminogen Activator Inhibitor-1: Mechanistic Implications for Obesity-associated Thrombosis
Authors: Ilya O Blokhin, Eric J Devor, Shyam Ramachandran, Prakash Doddapattar, Hong Jin, Anil K Chauhan, Paul B McCray, Kimberly K Leslie, Steven R Lentz
Journal: Circulation (2015)

Obesity is an epidemic in developed countries and is associated with an increased incidence of arterial and venous thrombosis. The mechanisms of obesity-induced thrombosis, however, are not well defined. In the current study, we tested the hypothesis that diet-induced obesity causes alterations in microRNA expression that may predispose to thrombosis. To induce obesity, C57Bl/6J mice were fed a 60% high fat diet. Compared with lean mice, obese mice had elevated fasting levels of glucose and insulin resistance, and exhibited acceleration of carotid artery thrombosis after photochemical injury (P&lt;0.01) and increased susceptibility to venous thrombosis induced by inferior vena cava ligation (P&lt;0.05). Plasma levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis secreted by adipocytes and endothelial cells, were elevated 3-fold in obese mice, suggesting a potential mechanism of thrombosis in diet-induced obesity. TaqMan low-density microRNA arrays detected downregulation of 41 microRNAs in plasma exosomes from obese mice (P&lt;0.05). Bioinformatic analysis of the downregulated microRNAs in relation to the PAI-1 3’-UTR identified microRNA-148a as a potential inhibitor of PAI-1 expression in obesity. We found that levels of PAI-1 mRNA were increased 4.5-fold (P&lt;0.05) and levels of microRNA-148a decreased 4-fold (P&lt;0.05) in white adipose tissue from obese mice compared with lean mice. Transfection of primary adipocytes or a murine endothelial cell line (MS-1) with a microRNA-148a mimetic resulted in 50-70% downregulation of PAI-1 expression (P&lt;0.05), demonstrating a causal inverse relationship between microRNA-148a and PAI-1 mRNA. Our findings suggest that downregulation of microRNA-148a in diet-induced obesity may promote thrombosis through loss of repression of PAI-1 expression at the mRNA level.
A comparison of surgical resection and transarterial chemoembolization for solitary hepatocellular carcinoma larger than 10 cm: A propensity score matching analysis
Authors: H.-S. Lu, C.-W. Su, W.-Y. Kao, T.-I. Huo, Y.-H. Huang, M.-C. Hou, H.-C. Lin, J.-C. Wu
Journal: Journal of Hepatology (2018)
Abstract 14896: Cardiovascular Events and Healthcare Utilization Among Long-term Adult Cancer Survivors Relative to Comorbidity-matched Controls
Authors: Kristopher Swiger, Jai Singh, Eric Farber-Eger, Javid Moslehi, Quinn Wells
Journal: Circulation (2017)

Background: Adult cancer survivors have higher rates of cardiovascular disease (CVD) and healthcare utilization (HCU) relative to the general population, but also have a greater burden of CVD risk ...
Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKD
Authors: Cheuk-Chun Szeto, Christopher William McIntyre, Philip Kam-Tao Li
Journal: Journal of the American Society of Nephrology (2018)

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.
T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate
Authors: Wataru Ise, Kentaro Fujii, Katsuyuki Shiroguchi, Ayako Ito, Kohei Kometani, Kiyoshi Takeda, Eiryo Kawakami, Kazuo Yamashita, Kazuhiro Suzuki, Takaharu Okada, Tomohiro Kurosaki
Journal: Immunity (2018)
Addressing the Homeless Mentally Ill in San Francisco
Authors: Ira D. Glick
Journal: American Journal of Psychiatry (2018)

San Francisco has long taken a compassionate approach to the homeless mentally ill.San Francisco was the first city to implement the Housing First model.The city offers a broad array of mental health and substance use disorder services, and it has pioneered programs that offer treatment in lieu of incarceration.In 2016, under the leadership of the late Mayor Ed Lee, the city took another step forward and consolidated its homelessness and supportive housing services under one department, guided by a strategic plan that seeks to solve homelessness based on individual needs.The city also participates in the state's Whole Person Care pilot program through the state's Medicaid program, and it is piloting the Law Enforcement Assisted Diversion program, which offers voluntary treatment and services as an alternative to arrest.Yet, despite these efforts and significant resource investments, we see on our streets a group of people who are triply diagnosed with medical/surgical/psychiatric illness, often with concurrent substance use disorder, unable to function or live outside of a structured care setting.California law allows people who meet criteria for "grave disability"-defined as an inability to feed, shelter, or clothe oneself-to be placed under conservatorships overseen by the county.Conservatorships may last up to 1 year, during which time the county provides for the individual's basic needs, medical care, and social supports through intensive case management.Unfortunately, the law does not include a history of substance use disorder as a criterion for meeting grave disability.Mayor Lee's hope was to fix the system so that we would have the resources to care humanely for the seriously mentally ill, exactly as our medicalsurgical colleagues do for serious medical illness.
Chemokine Receptor CXCR4−Targeted PET/CT With 68Ga-Pentixafor Shows Superiority to 18F-FDG in a Patient With Waldenström Macroglobulinemia
Authors: Yaping Luo, Qingqing Pan, Jun Feng, Xinxin Cao, Fang Li
Journal: Clinical Nuclear Medicine (2018)

Abstract A 69-year-old woman diagnosed with Waldenström macroglobulinemia (WM) was referred for 18 F-FDG and 68 Ga-Pentixafor PET/CT for evaluation of the disease. Extensive involvement of WM with intense radioactivity in the bone marrow and lymph nodes was found in 68 Ga-Pentixafor PET/CT. However, in 18 F-FDG PET/CT, the lesions showed significantly lower tracer uptake. Given the superiority of 68 Ga-Pentixafor in detecting WM lesions to 18 F-FDG in this patient, 68 Ga-Pentixafor PET/CT might be a promising imaging modality in assessment of tumor burden of WM in future studies.
Trump appoints “Dr Oz” to fitness, sports, and nutrition council
Authors: Owen Dyer
Journal: BMJ (2018)

Mehmet Oz, the medically qualified host of a US daytime television show frequently criticised for promoting false medical claims and dietary scams, has been appointed to President Donald Trump’s Council on Sports, Fitness, and Nutrition.

Trump has also renamed the council, which under President Obama was called the Council on Fitness, Sports, and Nutrition. The Obama administration added “nutrition” to its name, as the council worked on First Lady Michelle Obama’s healthy school lunch initiative. Under Trump it will focus on encouraging youth participation in sports, current administration sources said.

The council will meet with Trump on the …
Blood Glucose Readings Made Possible Via Smartphone
Authors: Rebecca Voelker
Journal: JAMA (2018)

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Clinical and molecular characterization of early-onset colorectal cancer patients with inflammatory bowel disease.
Authors: Alexandra Nicole Willauer, Jonathan M. Loree, Allan Andresson Lima Pereira, Michael Lam, Kanwal Pratap Singh Raghav, Van Karlyle Morris, David Menter, Kenna Rael Shaw, Russell Broaddus, Funda Meric-Bernstam, Yinghong Wang, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

689 Background: Recent reports suggest colorectal cancer incidence is steadily increasing in adults &lt; 50 years old. This population has a number of unique pre-disposing conditions, such as inflammatory bowel disease (IBD), that may alter the disease biology within these patients. Methods: Using a cohort of 1876 patients with metastatic CRC (mCRC), we identified 622 patients aged &lt; 50 years and reviewed their medical records for a diagnosis of IBD. Clinical, pathologic and overall survival (OS) were compared between patients with and without IBD in this age group. Results: Twenty of 622 (3.2%) early-onset mCRC patients had IBD. These patients were more likely to have mucinous or signet ring histologic features (50.0% vs 15.6%, OR 5.43, 95% CI 2.20-13.41, P &lt; 0.0001) and less likely to have APC mutations (15.0% vs 42.7%, P = 0.019). A trend toward an increased prevalence of right-sided location (40.0% vs 24.1%, P = 0.053) and TP53 mutations (85.0% vs 65.1%, P = 0.091) and decreased prevalence of PIK3CA mutations (0.0% vs 15.5%, P = 0.057) and KRAS mutations (35.0% vs 50.0%, P = 0.11) were noted. There were no differences in prevalence of BRAF V600 (P = 0.99), CTNNB1 (P = 0.99), NRAS (P = 0.99), PTEN (P = 0.43), or SMAD4 (P = 0.75) mutations between patients with IBD and other early-onset mCRC. The presence of IBD in early-onset mCRC patients was associated with a worse OS compared to patients without IBD but who had mCRC (HR 1.82, 95% CI 0.90-3.69, P = 0.026). Conclusions: Early-onset mCRC patients with IBD are significantly more likely to have mucinous or signet ring histologic features and have fewer mutations in canonical CRC genes such as KRAS, PIK3CA, and APC. This suggests that this population likely develops through a unique molecular pathogenesis and they may respond differently to therapy. Further molecular characterization of this population is required.
Clinical impact, morbidity and mortality of Hepatitis E at tertiary referral centres in central Europe
Authors: J. Hartl, P. Behrendt, M. Cornberg, K. Deterding, D. Westhölter, M. Luetgehetmann, A. Lohse, M.P. Manns, S. Pischke, H. Wedemeyer
Journal: Journal of Hepatology (2018)
P526Signal ways of hypoxia-induced cardioprotection in diabetic heart
Authors: A Portnychenko, M Vasylenko, V Babicheva, T Lapikova-Bryhinska, M Kolcheva, V Nosar, V Portnichenko
Journal: Cardiovascular Research (2018)

old animals, RIPC exhibited antiarrhythmic effect, while its impact on the severity of arrhythmias in eight months old SHR rats was negative.Aditionally, RIPC enhamced recovery of contractile function only in five months old animals, with no effect on contractility in three and eight months old rats.Protective effect of RIPC was associated with an increased Akt, ERK and GSK-3b phosphorylation as well as decreased Bax/Bcl-2 ratio and caspase-3 activation only in the groups of three and five months old animals.Conclusions: RIPC exhibited cardioprotective effects in SHR rats that were partially age-dependent.Whereas in older adult animals, RIPC decreased the extent of lethal injury, it did not attenuate myocardial stunning and aggravated arrhythmogenesis as compared to younger individuals.These effects of RIPC may be attributed to the differences in the activation of the components of RISK and appoptic pathway and a distinct influencing of various aspects of ischemia/reperfusion injury.
Impact of antibiotic prophylaxis of spontaneous bacterial peritonitis on colonization and infections with multidrug-resistant bacteria
Authors: M. Mücke, A. Mayer, J. Kessel, V.T. Mücke, K. Schwarzkopf, A. Vermehren, N. Weiler, M.W. Welker, J. Vermehren, V.A.J. Kempf, S. Zeuzem, C. Lange
Journal: Journal of Hepatology (2018)
TCTAP C-160 Thoracic Endovascular Aortic Repair for Aortic Dissection Complicated with Disseminated Intravascular Coagulation
Authors: Jeong Cheon Choe, Han Cheol Lee, Sun Hack Lee, Jinhee Ahn, Jin Sup Park, Hye Won Lee, Jun-Hyok Oh, Jung Hyun Choi, Kwang Soo Cha, Taek Jong Hong
Journal: Journal of the American College of Cardiology (2018)
ENDOSCOPIC FINDINGS IN AN INICIAL ROUND OF COLORECTAL CANCER SCREENING IN A POPULATION FROM 60 TO 70 YEARS OLD
Authors: DJ Matias, L Monteserín Ron, L Rodríguez Martín, S Vivas Alegre, R Díez Rodríguez, N Reyes Campos, G Molina Arriero, MI Fernández, E Fernández Morán, F Jorquera Plaza
Journal: Endoscopy (2018)

The incidence of colorectal cancer (CRC) increases significantly in people over 50 years. The colorectal cancer population screening programmes are starting to take place in different Spanish autonomic communities. We aimed to describe the endoscopic findings of the elderly patients included in the CRC screening programme.
Medical oncologists attitude toward end-of-life discussions: Effects of their experience, perceptions, and beliefs.
Authors: Masanori Mori, Chikako Shimizu, Asao Ogawa, Takuji Okusaka, Saran Yoshida, Tatsuya Morita
Journal: Journal of Clinical Oncology (2015)

e20503 Background: Although having timely end-of-life discussions (EOLd) with advanced cancer patients is essential to provide optimal end-of-life (EOL) care consistent with patients’ preferences and improve their quality of life, it often takes place late in the disease trajectory. The primary aim of this study was to clarify medical oncologists’ experience of EOLd, perceptions of good death, and beliefs contributing to EOLd timing. Methods: We conducted a nationwide survey of medical oncologists on EOLd timing regarding prognosis, hospice, preferred site of death, and do-not-resuscitate (DNR) status with advanced cancer patients. Multivariate analyses identified determinants of early discussions. Results: Among 490 physicians (response rate: 57%), 165 (34%), 65 (14%), 47 (9.8%), and 20 (4.2%) would discuss prognosis, hospice, preferred site of death, and DNR status, respectively, “now (at diagnosis)” with an assumed asymptomatic patient with newly diagnosed metastatic cancer. In multivariate analyses, determinants of discussing prognosis “now” included being a hematologist (odds ratio (OR), 1.68; p = 0.016), more physician-perceived importance of autonomy for good death (OR, 1.34; p = 0.014), and less perceived difficulty estimating the prognosis (OR, 0.77; p = 0.012). Determinants of discussing hospice “now” included no responsibility as treating physician at EOL (OR, 1.94; p = 0.031), more physician-perceived importance of life completion (OR, 1.58; p = 0.018), and less discomfort talking about death (OR, 0.67; p = 0.002). Determinants of discussing preferred site of death “now” included more physician-perceived importance of life completion (OR, 1.83; p = 0.008) and less discomfort talking about death (OR, 0.74; p = 0.034). The determinant of discussing DNR status “now” was less discomfort talking about death (OR, 0.49; p = 0.003). Conclusions: It may be helpful for medical oncologists to recognize that their own perception and beliefs can influence the attitude toward EOLd. Education programs including validated prognostic measures and skills to relieve discomfort talking about death would be valuable.