tbuckley/cabot-search huggingface dataset:
Inhibition of PKCδ reduces amyloid-β levels and reverses Alzheimer disease phenotypes
Authors: Ying Du, Yingjun Zhao, Chuan Li, Qiuyang Zheng, Jing Tian, Zhuyi Li, Timothy Y. Huang, Wei Zhang, Huaxi Xu
Journal: The Journal of Experimental Medicine (2018)

β-amyloid protein (Aβ) plays a central role in the pathogenesis of Alzheimer disease (AD). Aβ is generated from sequential cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) and the γ-secretase complex. Although activation of some protein kinase C (PKC) isoforms such as PKCα and ε has been shown to regulate nonamyloidogenic pathways and Aβ degradation, it is unclear whether other PKC isoforms are involved in APP processing/AD pathogenesis. In this study, we report that increased PKCδ levels correlate with BACE1 expression in the AD brain. PKCδ knockdown reduces BACE1 expression, BACE1-mediated APP processing, and Aβ production. Conversely, overexpression of PKCδ increases BACE1 expression and Aβ generation. Importantly, inhibition of PKCδ by rottlerin markedly reduces BACE1 expression, Aβ levels, and neuritic plaque formation and rescues cognitive deficits in an APP Swedish mutations K594N/M595L/presenilin-1 with an exon 9 deletion–transgenic AD mouse model. Our study indicates that PKCδ plays an important role in aggravating AD pathogenesis, and PKCδ may be a potential target in AD therapeutics.
Serial minimal residual disease (MRD) monitoring during first-line FCR treatment for CLL may direct individualized therapeutic strategies
Authors: Philip A. Thompson, Christine B. Peterson, Paolo Strati, Jeff Jorgensen, Michael J. Keating, Susan M. O’Brien, Alessandra Ferrajoli, Jan A. Burger, Zeev Estrov, Nitin Jain, Tapan M. Kadia, Gautam Borthakur, Courtney D. DiNardo, Naval Daver, Elias Jabbour, William G. Wierda
Journal: Leukemia (2018)
Two distinct mechanisms for experience-dependent homeostasis
Authors: Michelle C. D. Bridi, Roberto de Pasquale, Crystal L. Lantz, Yu Gu, Andrew Borrell, Se-Young Choi, Kaiwen He, Trinh Tran, Su Z. Hong, Andrew Dykman, Hey-Kyoung Lee, Elizabeth M. Quinlan, Alfredo Kirkwood
Journal: Nature Neuroscience (2018)
Abstract 4496: Percutaneous Coronary Intervention in Stable Coronary Heart Disease: Value of Nt-Probnp for Stratification of Long-Term Risk
Authors: Pedro Carmo, Carlos Aguiar, Jorge Ferreira, Luis Raposo, Pedro Goncalves, Manuel Almeida, Rui Teles, Joao Figueira, Francisco Machado, Aniceto Silva
Journal: Circulation (2008)

Purpose: N-terminal fragment of the B type-natriuretic peptide (NT-proBNP) is an established tool for assessing acute dyspnoea and stratifying risk in heart failure, acute coronary syndromes (ACS), and stable coronary heart disease (SCHD). The aim of this study was to determine the value of NT-proBNP in predicting long-term risk of patients (Pts) submitted to elective percutaneous coronary intervention (PCI) in the setting of SCHD. Methods: We prospectively studied 291 Pts (age 64.3±9.6 years, 64 female) with SCHD submitted to successful elective PCI, and determined NT-proBNP immediately before PCI. Pts were divided into 2 groups according to NT-proBNP level: group T3 formed by Pts with NT-proBNP level in the highest tertile and group T1+T2 formed by all remaining Pts. The study endpoint was time to the first occurrence of death (D) or non-fatal myocardial infarction (MI) during the mean follow-up of 568 ± 322 days. Multivariable analyses were performed to adjust the prognostic value of NT-proBNP for the effects of factors known to influence NT-proBNP (age, gender, renal function, body mass index) and of other potential predictors of outcome (cardiovascular risk factors, prior cardiovascular events, left ventricular ejection fraction, and PCI characteristics). Results: NT-proBNP ranged from 5 pg/ml to 104 pg/ml in the 1st tertile (T1), 105 pg/ml to 358 pg/ml in the 2nd tertile (T2), and 364 pg/ml to 33.991 pg/ml in the 3rd tertile (T3). During follow-up, 8 Pts died and 11 suffered a non-fatal MI. NT-proBNP was significantly higher in Pts who experienced an adverse outcome (440 pg/ml [inter-quartile range, 104 –1712] vs 174 pg/ml [inter-quartile range, 78 – 460) in Pts with uneventful follow-up; P= 0.007). An NT-proBNP level ≥364 pg/ml was associated with a higher endpoint rate (13.4% vs 3.1% in group T1+T2) and independently predicted outcome: adjusted hazard ratio 3.11, 95% CI, 1.15– 8.37, P=0.025. The sensitivity, specificity, predictive positive value, and negative predictive value for the criterion NT-proBNP ≥364 pg/ml were 68.4%, 69.1%, 13.4%, and 96.9%, respectively. Conclusion: In the setting of SCHD, the level of NT-proBNP is a powerful prognostic marker even after successful PCI.
Ursodeoxycholic acid treatment is associated with prolonged transplant-free survival in primary biliary cholangitis – even in patients without biochemical improvements
Authors: M. Harms, H. Van Buuren, W.J. Lammers, C. Corpechot, D. Thorburn, P. Invernizzi, H. Janssen, P.M. Battezzati, F. Nevens, K. Lindor, A. Floreani, C. Ponsioen, M.J. Mayo, A. Pares, A.L. Mason, K.V. Kowdley, G. Hirschfield, B. Hansen, A. Van der Meer
Journal: Journal of Hepatology (2018)
Endoscopic radiofrequency ablation for the treatment of gastric antral vascular ectasia in cirrhotic patients: A bi-centric clinical and economical cost-effective analysis
Authors: M. Senzolo, S. Realdon, B. Simoncin, A. Zanetto, S. Caronna, G.M. Saracco, C. De Angelis, W. Debernardi-Venon
Journal: Journal of Hepatology (2018)
Brief Report: Lupus—An Unrecognized Leading Cause of Death in Young Females: A Population‐Based Study Using Nationwide Death Certificates, 2000–2015
Authors: Eric Y. Yen, Ram R. Singh
Journal: Arthritis & Rheumatology (2018)

Objective Mortality statistics from the Centers for Disease Control and Prevention ( CDC ) are used for planning health care policy and allocating resources. The CDC uses these data to compile its annual ranking of leading causes of death based on a selected list of 113 causes. Systemic lupus erythematosus ( SLE ) is not included on this list. Since the ranking is a useful tool for assessing the relative burden of cause‐specific mortality, this study was undertaken to rank SLE deaths among the CDC 's leading causes of death to see whether SLE is a significant cause of death among females. Methods Death counts for the female population of the US were obtained from the CDC 's Wide‐ranging Online Data for Epidemiologic Research database and then grouped by age and race/ethnicity. Data on the leading causes of death were obtained from the Web‐based Injury Statistics Query and Reporting System database. Results During 2000–2015, there were 28,411 deaths of females with SLE recorded as an underlying or contributing cause of death. SLE ranked among the top 20 leading causes of death in females between 5 and 64 years of age. SLE ranked tenth among those ages 15–24 years, fourteenth among those ages 25–34 years and 35–44 years, and fifteenth among those ages 10–14 years. For African American and Hispanic females, SLE ranked fifth among those ages 15–24 years, sixth among those ages 25–34 years, and eighth or ninth among those ages 35–44 years, after the 3 common external injury causes of death were excluded from the analysis. Conclusion SLE is among the leading causes of death in young females, underscoring its impact as an important public health issue.
Novel pro-fibrotic properties of macrophage migration inhibitory factor in non-alcoholic steatohepatitis is associated with a shift in natural killer T cell populations
Authors: D. Heinrichs, E.F. Brandt, P. Fischer, J. Koehncke, T. Wirtz, S. Djudjaj, P. Boor, R. Bucala, D. Kroy, F. Schumacher, H. Wasmuth, C. Trautwein, Jürgen Bernhagen, M.-L. Berres
Journal: Journal of Hepatology (2018)
Response to: ‘Time to personalise the treatment of anti-MDA-5 associated lung disease’ by Lake <i>et al</i>
Authors: Valérie Leclair, Ingrid E Lundberg, Anna Tjärnlund
Journal: Annals of the Rheumatic Diseases (2018)

We have with interest read the comments raised by Lake et al in the e-letter titled ‘Time to personalise the treatment of anti-MDA-5 associated lung disease’ to be published in your journal.1 We thank the authors for sharing their insights on the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.2 Lake and colleagues are concerned that these classification criteria are not including rare specific subsets such as dermatomyositis (DM) or amyopathic DM associated with antimelanoma differentiation-associated protein 5 (MDA5). They fear that this will in turn prevent clinicians and researchers from exploring new therapeutic approaches for this population frequently affected by rapidly progressive interstitial lung disease (RPILD), a complication associated with fatal outcomes.3 4 Dr Malaviya raised a similar concern when discussing the importance of myositis-specific autoantibodies (MSA) in classifying subgroups of IIM, exemplified by …
Gp38+ hepatic progenitor cell-derived large extracellular vesicles in biliary cancers – a novel liquid biopsy marker?
Authors: S. Urban, M. Krawczyk, A. Willms, J. Ligocka, H. Sänger, K. Jankowski, M. Krawczyk, K. Zieniewicz, W. Patkowski, R. Schwab, A. Wöhler, S. Gehlert, J.M. Banales, P. Milkiewicz, F. Lammert, V. Lukacs-Kornek, M. Kornek
Journal: Journal of Hepatology (2018)
FXR is a proviral factor whose binding to HBV genome is modulated by FXR agonist and correlates with presence of the activated chromatin mark H3K4me3 in an HBx dependant manner
Authors: B. Lacombe, K. Mouzzanar, C. Ménard, V. Lotteau, C. Ramière, P. Andre
Journal: Journal of Hepatology (2018)
HCV genetic diversity by geographic region within genotype 1-6 subtypes among patients treated with Glecaprevir and Pibrentasvir
Authors: G. Schnell, R. Tripathi, P. Krishnan, J. Beyer, T. Reisch, M. Irvin, T. Dekhtyar, L. Lu, I.C. Ng, W. Xie, T. Pilot-Matias, C. Collins
Journal: Journal of Hepatology (2018)
Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update
Authors: Junmin Zhang, Baoxin Zhang, Xinming Li, Xiao Han, Ruijuan Liu, Jianguo Fang
Journal: Medicinal Research Reviews (2018)

Abstract Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C‐terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.
Scale up of hepatitis C virus treatment in the era of all-oral direct-acting antivirals: a 9-year Greek cohort study
Authors: V. Papastergiou, M. Deutsch, M. Mela, C. Triantos, H. Kranidioti, C. Chatzievangelinou, K. Zisimopoulos, O. Anagnostou, G. Papatheodoridis, S. Manolakopoulos
Journal: Journal of Hepatology (2018)
T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation
Authors: Eric Tu, Cheryl P.Z. Chia, Weiwei Chen, Dunfang Zhang, Sang A. Park, Wenwen Jin, Dandan Wang, Maria-Luisa Alegre, Ying E. Zhang, Lingyun Sun, WanJun Chen
Journal: Immunity (2018)
Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa
Authors: Olatunde Olayanju, Jason Limberis, Aliasgar Esmail, Suzette Oelofse, Phindile Gina, Elize Pietersen, Mohammed Fadul, Rob Warren, Keertan Dheda
Journal: European Respiratory Journal (2018)

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking. We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL −1 ) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition). The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p&lt;0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p&lt;0.001) and default (1.5% versus 15.2%; p&lt;0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight &gt;50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count). XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.
Data chart: what do trainees do after completing foundation training?
Authors: Tom Moberly
Journal: BMJ (2018)

Less than half of all doctors training in the UK now move directly from foundation training to specialty training, with most now taking a break from training at this stage, figures from the UK Foundation Programme Office (UKFPO) show.

The proportion of doctors going directly from foundation training into specialty training has fallen steadily since 2009, when …
Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study
Authors: Alessandro Marcon, Francesca Locatelli, Dirk Keidel, Anna B Beckmeyer-Borowko, Isa Cerveri, Shyamali C Dharmage, Elaine Fuertes, Judith Garcia-Aymerich, Joachim Heinrich, Medea Imboden, Christer Janson, Ane Johannessen, Bénédicte Leynaert, Silvia Pascual Erquicia, Giancarlo Pesce, Emmanuel Schaffner, Cecilie Svanes, Isabel Urrutia, Deborah Jarvis, Nicole M Probst-Hensch, Simone Accordini
Journal: Thorax (2018)

Background It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. Objective We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. Methods We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st–3rd quartiles: 29–44) by their level of airway responsiveness using quintiles of methacholine dose–response slope at the first examination (1991–1994). Then, we excluded subjects with airflow obstruction at the second examination (1999–2003) and analysed incidence of COPD (postbronchodilator FEV 1 /FVC below the lower limit of normal) at the third examination (2010–2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. Results We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose–response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. Conclusions Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.
Efficacy and safety of glecaprevir/pibrentasvir in renally-impaired patients with chronic hepatitis C virus genotype 1–6 infection
Authors: M. Persico, R. Flisiak, M. Abunimeh, M. Sise, J.Y. Park, M. Kaskas, A. Bruchfeld, M.-A. Wörns, A. Aglitti, Z. Xue, J. Rullman, A. Pocalla, E. Lawitz
Journal: Journal of Hepatology (2018)
Recent Advances in the Development of Antimicrobial Nanoparticles for Combating Resistant Pathogens
Authors: Rajamani Lakshminarayanan, Enyi Ye, David James Young, Zibiao Li, Xian Jun Loh
Journal: Advanced Healthcare Materials (2018)

Abstract The rapid growth of harmful pathogens and their multidrug‐resistance poses a severe challenge for health professionals and for the development of new healthcare products. Various strategies are exploited for the development of effective antimicrobial agents, and nanoparticles are a particularly promising class of materials in this respect. This review summarizes recent advances in antimicrobial metallic, polymeric, and lipid‐based nanoparticles such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers. The latter materials in particular are engineered for antimicrobial agent delivery and act by encapsulation, receptor‐based binding, and disruption of microbial adherence to cellular substrates. Potential strategies for the design of multifunctional antimicrobial nanocarriers, combining material chemistry and biological interface science, are also discussed.
P370endothelin-1 gene lys198asn polymorphism in men with essential hypertension complicated and uncomplicated with chronic heart failure
Authors: H Palahniuk, V M Jebel, O M Pavliuk
Journal: Cardiovascular Research (2018)

vivo.In addition, treatment with Fx prevents SMC proliferation and neointima lesion formation.This new factor may hold promise as a novel therapeutic tool to enhance functional EC recovery and prevent neointima formation.
Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis
Authors: Eva-Maria Siegmann, Helge H. O. Müller, Caroline Luecke, Alexandra Philipsen, Johannes Kornhuber, Teja Wolfgang Grömer
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> With a prevalence of 4% to 13% in the United States, autoimmune thyroiditis (AIT) is a major health problem. Besides somatic complications, patients with AIT can also experience psychiatric disorders. The extent of these organic psychiatric diseases in patients with AIT, however, is so far not commonly known. <h3>Objective</h3> To provide meta-analytic data on the association of depression and anxiety with AIT. <h3>Data Sources</h3> Google Scholar, the EBSCO Host databases, the Web of Knowledge, and PubMed were searched from inception through December 5, 2017. Articles identified were reviewed and reference lists were searched manually. <h3>Study Selection</h3> Case-control and epidemiological studies that reported the association between AIT and either depression or anxiety disorders or both were included. <h3>Data Extraction and Synthesis</h3> Data extraction was performed by multiple observers following the PRISMA guidelines. Two univariate random-effects meta-analyses were performed, and moderators were tested with Bonferroni-corrected meta-regression analysis. Heterogeneity was assessed with the<i>I</i><sup>2</sup>statistic. Sensitivity analyses tested the robustness of the results. Small study effects were assessed with funnel plots and the Egger test. <h3>Main Outcomes and Measures</h3> The odds ratio of patients with AIT and depression compared with a healthy control group, as well as the odds ratio of patients with AIT and anxiety disorders compared with a healthy control group. <h3>Results</h3> Twenty studies comprising 22 independent samples were included, with a total of 44 388 participants (43 382 for depression and 34 094 for anxiety). Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.31 (95% CI, 2.00-5.48;<i>I</i><sup>2</sup> = 92.6%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85;<i>I</i><sup>2</sup> = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean [SD] score: anxiety, 5.77 [1.17]; depression, 5.67 [1.11]; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did. <h3>Conclusions and Relevance</h3> This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment—and not only psychotherapeutic treatment—of the organic disorder.
Soluble cytotoxic T-lymphocyte-associated antigen-4 and soluble programmed cell death protein-1 are predictive immune checkpoint seromarkers for spontaneous functional cure of chronic hepatitis B with opposite effects
Authors: H.-I. Yang, H.-H. Hu, M.-H. Pan, W.-S. Luo, R.W.-J. Jeng, C.-Y. Su, C.-T. Chiang, C.-L. Jen, S.-N. Lu, L.-Y. Wang, M.-H. Lee, J. Liu, M. Nguyen, C.-J. Chen
Journal: Journal of Hepatology (2018)
Hepatoprotective biomarkers, amphiregulin and soluble Fas, increase during ELAD treatment in alcoholic hepatitis subjects
Authors: P. Bedard, J. Lapetoda, L. Landeen, A. Al-Khafaji, A. Parikh, A. Duarte-Rojo, B. Borg, G. Mccaughan, L. Stein, L. Teperman, M. Allison, N. Shah, R. Subramanian, R. Malik, R. Brown, R. Macnicholas, S. Habib, S. Asrani, T. Adhami
Journal: Journal of Hepatology (2018)
Expert consensus on the evaluation and diagnosis of combat injuries of the Chinese People’s Liberation Army
Authors: Zhao-wen Zong, Lian-yang Zhang, Hao Qin, Si-xu Chen, Lin Zhang, Lei Yang, Xiao-xue Li, Quan-wei Bao, Dao-cheng Liu, Si-hao He, Yue Shen, Rong Zhang, Yu-feng Zhao, Xiao-zheng Zhong
Journal: Military Medical Research (2018)

The accurate assessment and diagnosis of combat injuries are the basis for triage and treatment of combat casualties. A consensus on the assessment and diagnosis of combat injuries was made and discussed at the second annual meeting of the Professional Committee on Disaster Medicine of the Chinese People's Liberation Army (PLA). In this consensus agreement, the massive hemorrhage, airway, respiration, circulation and hypothermia (MARCH) algorithm, which is a simple triage and rapid treatment and field triage score, was recommended to assess combat casualties during the first-aid stage, whereas the abbreviated scoring method for combat casualty and the MARCH algorithm were recommended to assess combat casualties in level II facilities. In level III facilities, combined measures, including a history inquiry, thorough physical examination, laboratory examination, X-ray, and ultrasound examination, were recommended for the diagnosis of combat casualties. In addition, corresponding methods were recommended for the recognition of casualties needing massive transfusions, assessment of firearm wounds, evaluation of mangled extremities, and assessment of injury severity in this consensus.