tbuckley/cabot-search huggingface dataset:
Pharmacoepigenetics and Toxicoepigenetics: Novel Mechanistic Insights and Therapeutic Opportunities
Authors: Volker M. Lauschke, Isabel Barragan, Magnus Ingelman-Sundberg
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Pharmacological treatment and exposure to xenobiotics can cause substantial changes in epigenetic signatures. The majority of these epigenetic changes, caused by the compounds in question, occur downstream of transcriptional activation mechanisms, whereby the epigenetic alterations can create a transcriptional memory and stably modulate cell function. The increasing understanding of epigenetic mechanisms and their importance in disease has prompted the development of therapeutic interventions that target epigenetic modulatory mechanisms, particularly in oncology where inhibitors of epigenetic-modifying proteins (epidrugs) have been successfully used in treatment, mostly in combination with standard-of-care chemotherapy, either provoking direct cytotoxicity or inhibiting resistance to anticancer drugs. In addition, emerging methods for detecting epigenetically modified DNA in bodily fluids may provide information about tumor phenotype or drug treatment success. However, it is important to note that many technical pitfalls, such as the nondeconvolution of methylcytosine and hydroxymethylcytosine, compromise epigenetic analyses and the interpretation of results. In this review, we provide an update on the field, with an emphasis on the novel therapeutic opportunities made possible by epidrugs.
The role of bacterial infection (BI) in decompensated cirrhosis patients with or without acute-on-chronic liver failure (ACLF)
Authors: Z. Cao, X. Lu, Z. Li, L. Chen, Y. Liu, R. Mo, P. Ren, L. Chen, J. Lu, X. Wang, G. Zhao, W. Tang, X. Xiang, H. Wang, W. Cai, H. Li, Q. Xie
Journal: Journal of Hepatology (2017)
High incidence of persistently altered liver tests after sustained virological response with direct-acting antiviral in hepatitis C monoinfected and HIV-coinfected patients
Authors: M. Montes, L. Domínguez, P. Castillo, J. García-Samaniego, L. Martín-Carbonero, E. Valencia, V. Moreno, J.R. Larrubia, M. Romero, A. García, J.C. Erdozain, J. González, A. Olveira
Journal: Journal of Hepatology (2017)
Clinical Outcomes in Adults/Adolescents with Hemophilia B Treated Long Term with Recombinant Factor IX Fc Fusion Protein (rFIXFc) Prophylaxis: Interim Results of the B-Yond Extension Study
Authors: Tadashi Matsushita, Johnny Mahlangu, Amy D Shapiro, K John Pasi, Margaret V. Ragni, Margareth C Ozelo, Johannes Oldenburg, Ross I Baker, Huixing Yuan, Alejandra Ramirez-Santiago, Francesca Ferrante, Stefan Lethagen
Journal: Blood (2016)
Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Celecoxib in Addition to Standard Chemotherapy for Advanced Non–Small-Cell Lung Cancer With Cyclooxygenase-2 Overexpression: CALGB 30801 (Alliance)
Authors: Martin J. Edelman, Xiaofei Wang, Lydia Hodgson, Richard T. Cheney, Maria Q. Baggstrom, Sachdev P. Thomas, Ajeet Gajra, Erin Bertino, Karen L. Reckamp, Julian Molina, Joan H. Schiller, Kisha Mitchell-Richards, Paula N. Friedman, Jon Ritter, Ginger Milne, Olwen M. Hahn, Thomas E. Stinchcombe, Everett E. Vokes
Journal: Journal of Clinical Oncology (2017)

Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression ≥ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index ≥ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index ≥ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 ≥ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.
Donald James Fairclough
Authors: Christine Bishop
Journal: BMJ (2017)

Donald James Fairclough was born in south Yorkshire to a general practitioner father and a former ward sister mother. Even so, his course into medicine was not entirely straightforward.

After school in Doncaster and five years at Bradfield College, he completed national service with the Green Howards, finishing as a second lieutenant in the Middle East. After Egypt, Khartoum, and the Red Sea, returning to take the Cambridge entrance exam held little appeal. Donald was …
Receptor-interacting protein kinase 3 acts differently according to non-alcoholic fatty liver disease model
Authors: W.K. Saeed, D.W. Jun, S.B. Ahn, J.S. Lee, Y.J. Chae, H.W. Oh, J.Y. Jeong, H.T. Kang, J.H. Sohn, E.C. Jang
Journal: Journal of Hepatology (2017)
‘Adulterant or contaminant in MT-45, or coingestion?’ Reply from the authors
Authors: A. Helander, M. Bradley, J. Lapins
Journal: British Journal of Dermatology (2017)

In a commentary to our publication entitled “Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45”,[1] Yip and Deng [2] argue that the lack of opioid symptoms would indicate involvement of another drug class, possibly arsenic or 2,4-dinitrophenol (DNP). In this respect, it should be emphasized that the patients did not seek hospital care for acute opioid overdose symptoms but for unexpected, late adverse side effects involving the skin, hair, and eyes.

This article is protected by copyright. All rights reserved.
Revisiting the History and Importance of Phototherapy in Dermatology
Authors: Merrick Brodsky, Michael Abrouk, Patrick Lee, Kristen M. Kelly
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Implementation of quality management for clinical bacteriology in low-resource settings
Authors: B. Barbé, C.P. Yansouni, D. Affolabi, J. Jacobs
Journal: Clinical Microbiology and Infection (2017)

The declining trend of malaria and the recent prioritization of containment of antimicrobial resistance have created a momentum to implement clinical bacteriology in low-resource settings. Successful implementation relies on guidance by a quality management system (QMS). Over the past decade international initiatives were launched towards implementation of QMS in HIV/AIDS, tuberculosis and malaria.To describe the progress towards accreditation of medical laboratories and to identify the challenges and best practices for implementation of QMS in clinical bacteriology in low-resource settings.Published literature, online reports and websites related to the implementation of laboratory QMS, accreditation of medical laboratories and initiatives for containment of antimicrobial resistance.Apart from the limitations of infrastructure, equipment, consumables and staff, QMS are challenged with the complexity of clinical bacteriology and the healthcare context in low-resource settings (small-scale laboratories, attitudes and perception of staff, absence of laboratory information systems). Likewise, most international initiatives addressing laboratory health strengthening have focused on public health and outbreak management rather than on hospital based patient care. Best practices to implement quality-assured clinical bacteriology in low-resource settings include alignment with national regulations and public health reference laboratories, participating in external quality assurance programmes, support from the hospital's management, starting with attainable projects, conducting error review and daily bench-side supervision, looking for locally adapted solutions, stimulating ownership and extending existing training programmes to clinical bacteriology.The implementation of QMS in clinical bacteriology in hospital settings will ultimately boost a culture of quality to all sectors of healthcare in low-resource settings.
Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: A cohort study
Authors: Chia‐Chi Wang, Jia‐Horng Kao
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article by Joo et al.1 In this study involving 83,339 participants without nonalcoholic fatty liver disease (NAFLD) at baseline, 20,200 incident NAFLD cases were identified during a median follow‐up period of 6.6 years. The adjusted hazard ratio of hepatitis B surface antigen (HBsAg)‐positive participants for incident NAFLD was 0.83 compared with HBsAg‐negative participants. After adjustment for confounders, the association between hepatitis B virus (HBV) infection and decreased risk of incident NAFLD remained, suggesting HBV infection may have a protective effect on the development of NAFLD. Although this large‐scale cohort study improves our understanding about the relationship between HBV infection and the development of NAFLD, several issues deserve discussion and further investigation. First, this study showed a decreased risk of incident NAFLD in HBsAg‐positive participants, even having larger body mass index and higher percentage of obesity at baseline compared with HBsAg‐negative participants. Furthermore, the favorable lipid profiles in HBsAg‐positive subjects such as lower triglyceride, cholesterol, and low‐density lipoprotein, as well as higher high‐density lipoprotein, may explain the decreased risk of NAFLD development. These results were consistent with our previous observations, suggesting chronic HBV infection protects against the development of NAFLD possibly due to a lower frequency of dyslipidemia profiles.2 However, the mechanisms involved in altered lipid metabolism by persistent HBV infection remain largely unclear and require additional study. Second, NAFLD is considered to be the liver manifestation of metabolic syndrome, which is associated with insulin resistance. Although chronic hepatitis C virus infection is known to be associated with insulin resistance, the relationship between HBV infection and insulin resistance has been inconclusive.3 In this study, baseline insulin resistance using homeostatic model assessment‐insulin resistance (HOMA‐IR) was comparable between HBsAg‐positive and HBsAg‐negative subjects. To clarify the complex interaction between HBV infection, NAFLD, and insulin resistance, the authors may compare HOMA‐IR between HBsAg‐positive and HBsAg‐negative subjects at the last visit to see whether chronic HBV infection affects insulin resistance. Third, because metabolic syndrome and its components can accelerate the progression of liver disease to cirrhosis and even hepatocellular carcinoma in patients with chronic HBV infection, it is imperative to realize which factors could predict the development of NAFLD in these patients.3 The authors may perform a subgroup analysis to identify the risk factors associated with the incident NAFLD in HBsAg‐positive subjects and then modify them with lifestyle modification or medications to reduce the progression of liver damage.
Distress in cancer survivors attending a multidisciplinary survivorship clinic.
Authors: Tara Beth Sanft, Lianne Epstein, Scott Capozza, Maura Harrigan, Mae Anne Jauk, Angela Khairallah, Jessica Jorge, Lara Sokoloff, Sophia Chen, Anees B. Chagpar, Melinda L Irwin
Journal: Journal of Clinical Oncology (2015)

9575 Background: Distress is defined as an unpleasant emotional experience that may interfere with the ability to cope with cancer or its treatment. Distress screening is recommended during transitions including survivorship. We describe distress in cancer survivors before and after participation in a multidisciplinary survivorship clinic. Methods: All patients participating in the Yale Adult Survivorship Clinic were asked to complete the National Comprehensive Cancer Network Distress Thermometer (DT) immediately before and after a visit. Survivors ranked distress from 0 (none) to 10 (extreme) and indicated associated problems from a 39-item list. A score ≥ 4 was considered clinically significant. Survivors were seen by an MD/APRN, social worker, registered dietitian and physical therapist. Survivors received individual counseling on topics including survivorship care, diet and exercise, and coping. All were offered a follow-up visit approximately 8 weeks later. Distress screening was repeated at the follow-up visit. Distress scores before and after each visit were compared using paired t-tests. Results: 377 survivors completed DTs before and after a survivorship clinic visit in 18 months. Survivors were mostly female (91%), white (77.2%), with a history of breast cancer (73%). The mean distress score prior to the initial visit was 4.82 (+/-2.82), and 2.45 (+/-2.15) after the visit (mean change -2.34, +/- 2.06, p < 0.0001). The top problems identified were worry (53%), fatigue (43%), and fears (30%). 191 survivors (51%) had clinically significant distress ( ≥ 4) before the initial visit; however, only 74 (20%) reported significant distress after the visit (p < 0.001) Of survivors who returned for a follow-up visit (N = 107), avg distress score was 4.20+/-2.97 before and 1.86+/-2.01 after (mean change -2.42, +/- 2.50 p < 0.0001). At the follow-up, 49 (46%) had clinically significant distress before and 17 (16%) after (p < 0.0001). Conclusions: More than half of all survivors participating in a multidisciplinary survivorship clinic reported clinically significant distress. Distress scores were significantly lower after the visit. These results suggest participation in a survivorship clinic is an intervention for distress.
Development and validation of a survival calculator for hepatocellular carcinoma patients undergoing liver transplantation: the Metroticket 2.0 model
Authors: Carlo Sposito, Alessandro Cucchetti, Jian Zhou, Antonio D. Pinna, Luciano De Carlis, Marco Bongini, Matteo Cescon, Jia Fan, Stefano Di Sandro, He Yi-feng, Andrea Lauterio, Vincenzo Mazzaferro
Journal: Journal of Hepatology (2017)
Reduced hepatitis B and D viral entry using novel clinically-applied inhibitors of the sodium taurocholate co-transporting polypeptide
Authors: J. Donkers, B. Zehnder, G. van Westen, A. IJzerman, M. Kwakkenbos, S. Urban, R.O. Elferink, S. van de Graaf
Journal: Journal of Hepatology (2017)
FDG PET/CT in Aortic Valve Bioprosthesis Infection
Authors: Lucia Rampin, Alice Ferretti, Maria Cristina Marzola, Lolita Sasset, Sotirios Chondrogiannis, Anna Maria Cattelan, Domenico Rubello, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2017)

A 62-year-old man presented with persistent fever, weakness, and retrosternal pain 3 years after aortic valve bioprosthesis (AVR). His white blood cell count was 11,000/μL and C-reactive protein was 13.6 mg/dL. Consecutive blood cultures isolated Staphylococcus epidermidis and capitis. Transesophageal echocardiography demonstrated small aortic valve prosthesis vegetation. F-FDG PET/CT revealed prominent AVR activity, SUVmax = 12.2. He was treated with daptomycin, meropenem, and gentamicin for 1 month and followed by daptomycin and carbapenem for 3 months. Follow-up F-FDG PET/CT at 6 months demonstrated complete clearing of AVR activity associated with full asymptomatic recovery.
Response to 1) Sertoglu et al – proper use of fatty acid levels to assess cardiovascular health, and 2) Lucas – n6/n3 ratio and health: what is the usefulness of a good divided by good?
Authors: Jason Hy Wu, Rozenn N. Lemaitre, Irena B. King, Xiaoling Song, Bruce M Psaty, David S. Siscovick, Dariush Mozaffarian
Journal: Circulation (2015)

Sertoglu and colleagues express concern about measurement of circulating fatty acid biomarkers in plasma. However, our investigation did not measure fatty acids in total plasma (the sum of fatty acids in non-esterified fatty acids, cholesterol esters, triglycerides, and phospholipids), but in the plasma phospholipid fraction. The plasma phospholipid fraction reflects fatty acid concentrations in cell membranes. Furthermore, phospholipid fatty acids in plasma and erythrocyte membranes inter-exchange, reflect fatty acid consumption over a similar period of time, and are reasonably correlated.1 Thus, either plasma phospholipid or erythrocyte fatty acid composition is a valid and reliable biomarker of dietary consumption. This explains why numerous longitudinal investigations have evaluated associations of fatty acids in plasma phospholipids or erythrocyte phospholipids in relation to cardio-metabolic disease risk.2, 3

We appreciate Sertoglu’s interest in omega-3 polyunsaturated fatty acids (n-3 PUFA). As described and cited in the present investigation, we previously measured and reported associations between plasma phospholipid n-3 PUFA biomarkers and risk of total and cardiovascular mortality in this cohort.4 In addition, in the current investigation we evaluated and found little evidence of interaction between linoleic acid (the major dietary omega-6 fatty acid) and n-3 PUFA (P=0.54). Indeed, our findings suggested an additive benefit, in that those with highest levels of both linoleic acid and n-3 PUFA had the lowest risk of total and cardiovascular mortality (figure 3, supplement figure 2).5 This important finding would have been obscured using an analysis based on the n-6/n-3 ratio. The conceptual and biologic flaws of the n-6/n-3 ratio have been described.6 A key flaw is the inability to discern very different conditions of dietary intake or underlying physiology: e.g., a ratio may be identical when consumption and circulating levels of both n-6 and n-3 are high or when both are low, two very different circumstances. In addition, the ratio cannot distinguish increases in the n-6 PUFA vs. decreases in n-3 PUFA. Finally, the conceptual basis of the ratio depends on the notion that n-6 PUFA and n-3 PUFA have opposing effects. However, substantial evidence indicates that both are beneficial;6 indeed, a recent meta-analysis found that individuals with higher circulating levels of arachidonic acid, the prototypical n-6 PUFA thought to be pro-inflammatory and harmful, had lower risk of coronary disease.7 Given these considerations, we agree with Dr Lucas that existing evidence suggest beneficial effect of dietary linoleic acid for cardiovascular outcomes, not harm, and use of the n-6/n-3 ratio is unlikely to impart meaningful information over and above assessment of the individual fatty acids alone.
Clinical impact of the early alanine amininotransferase flare during tenofovir monotherapy in treatment-naïve patients with chronic hepatitis B
Authors: Hee Yeon Seo, Han Ah Lee, Soon Young Ko, Joon Ho Wang, Jeong Han Kim, Won Hyeok Choe, So Young Kwon
Journal: Clinical and Molecular Hepatology (2017)

Little is known about the effect of early flares on response during first-line tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB). The aim of this study was to investigate the incidence and outcome of early alanine aminotransferase (ALT) flare in treatment-naive patients with CHB during long-term TDF monotherapy.One hundred eighty-one treatment-naive CHB patients were treated with a 300-mg once-daily dose of TDF for more than 12 weeks. Virological markers of hepatitis B virus (HBV) and biochemical data were measured at baseline and every 4-12 weeks during the therapy. The proportion of patients with undetectable HBV DNA level (< 100 copies/mL) was noted.The median age was 48.3 years and 122 patients (67.4%) were men. Hepatitis B envelope antigen (HBeAg) was positive in 101 patients (55.8%). No patient had cirrhosis. The median follow-up duration was 45 weeks (12-155 weeks). ALT flare (>5 × upper limit of the normal range) occurred in seven patients (3%) without viral breakthrough within the first 8 weeks after the start of TDF monotherapy. Among them, six patients were HBeAg-positive and one patient was HBeAg-negative. All cases of early ALT flares resolved within 4 weeks and virologic response was observed in all patients without interruption or discontinuation of treatment.Continuous TDF monotherapy was effective and safe in treatment-naive patients with CHB who experienced early ALT flares followed by a decrease in HBV DNA level.
Slow infusion of furosemide and albumin with or without terlipressin safely mobilizes ascites and impacts hemodynamics and intestinal permeability in ACLF patients with organ failure(s) and improves 28-day survival
Authors: G. Pande, S. Shalimar, K. Kumar, P.N. Sharma, V.P. Krishna, S. Mohindra, V.A. Saraswat
Journal: Journal of Hepatology (2017)
Elbasvir/Grazoprevir effectiveness in patients with Chronic Hepatitis C and Chronic Kidney Disease: real-world experience from the TRIO Network
Authors: Z. Younossi, B. Bacon, M. Curry, D. Dieterich, S. Flamm, K. Kowdley, S. Milligan, C. Nwankwo, N. Tsai, N. Afdhal
Journal: Journal of Hepatology (2017)
Discovery to first-in-man studies of a multi-peptide-based hepatocellular carcinoma vaccine adjuvanted with CV8102 (RNAdjuvant) – HEPAVAC
Authors: A. Mayer, R. Accolla, Y.T. Ma, R. Heidenreich, A. Koenigsrainer, F. Izzo, M. Loeffler, C. Flohr, P. Mueller, S. Kutscher, H.-G. Rammensee, B. Sangro, S. Francque, D. Valmori, T. Weinschenk, C. Reinhardt, U. Gnad-Vogt, H. Singh-Jasuja, L. Buonaguro
Journal: Journal of Hepatology (2017)