tbuckley/cabot-search huggingface dataset:
Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase mutations
Authors: Hilario Nunes, Florence Jeny, Diane Bouvry, Clément Picard, Jean-François Bernaudin, Christelle Ménard, Pierre-Yves Brillet, Caroline Kannengiesser, Dominique Valeyre, Marianne Kambouchner
Journal: European Respiratory Journal (2017)

We read with great interest the article by Newton et al . [1]. They found that mutations in the telomere maintenance machinery genes (telomerase reverse transcriptase ( TERT ), telomerase RNA component ( TERC ), regulator of telomere elongation helicase 1 and poly(A)-specific ribonuclease) led to variable interstitial lung disease (ILD) phenotypes that were universally progressive [1]. We were particularly interested by the evidence for the first time in the literature of a telomere-related gene mutation associated with pleuroparenchymal fibroelastosis (PPFE). PPFE represented eight out of the 77 (10.4%) cases with genetic aberrations, which is intriguing compared with the rarity of disease among ILDs. Indeed, a possible familial propensity for the development of PPFE was originally suggested by our earlier report of three affected sisters [2]. According to other published studies, a family history of ILD is observed in 17–57% of PPFE patients [3–5]. Five cases with telomerase reverse transcriptase mutation and pleuroparenchymal fibroelastosis <http://ow.ly/u33930aARaL>
Netlines
Authors: H. Brown
Journal: BMJ (2001)

Until recently, I was pretty confident that I was good at dealing with uncertainty. After all, I thought, it goes with the territory in medicine and particularly in general practice. Every day I have to make decisions and live with the outcomes in uncertain clinical situations. The common scenarios in general practice all involve weighing up probabilities and accepting varying degrees of uncertainty. When faced with the child with a fever and not much in the way of physical signs, the doctor takes a quick decision to treat the fever as a simple viral infection while trying to anticipate the less likely—but more worrying—possibilities.

> This was uncertainty of an entirely different order. This was me! 

With experience you learn that the unlikely does sometimes happen. Young men with healthy lifestyles and no risk factors do have heart attacks, and lifelong smokers can be healthy at 100. Inevitably, there are occasions when you get caught out and then you either live with your misdiagnosis and learn from it, or you collapse …
Hepatitis C: year 1 real life results from the All Wales hepatitis C roll out programme
Authors: D. Samuel, R. Alcolado, M. Czajkowski, N. Reeve, I. Rees, P. Hams, G. Hardcastle, K. Mitchell, R. Gale, A. Andrew, B. Ball, C.L. Ch’ng, D. Tomkinson, D. Blinston, A. Davies, H. Ryan, T. Mathialahan, S. Nicholas, E. Alexander, L. Mapp, S. Walsh, K. Rockey, J. Rees, W. Ahmed, A. Thompson, C. Sutton, T. Grenier, S. Kneath, L. Johnson, H. Edwards, O. Sitta, T. Jones, B. Healy
Journal: Journal of Hepatology (2017)
Clinical and virological characteristics of patients with chronic hepatitis C virus (HVC) infection and failure to multiple direct acting antiviral (DAA) therapies
Authors: J. Vermehren, J. Dietz, E. Schott, S. Mauss, J. Rockstroh, B. Müllhaupt, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2017)
Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas
Authors: Narumol Silpa-Archa, James L. Griffith, Richard H. Huggins, Marsha D. Henderson, Holly A. Kerr, Gordon Jacobsen, Sanjeev V. Mulekar, Henry W. Lim, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2017)
Prospective validation of serum alkaline phosphatase for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis
Authors: C. Levy, B. Eksteen, M. Shiffman, H. Janssen, A. Montano-Loza, D. Ding, C. Jia, B. Mccolgan, R. Myers, M. Subramanian, J. McHutchison, R. Chapman, M. Manns, Z. Goodman, C. Bowlus, A. Muir, G. Hirschfield
Journal: Journal of Hepatology (2017)
Global micro RNA expression profiling in the liver biopsies of Hepatitis B Virus infected patients identifies specific miRNA signatures related to viral persistence and hepatocellularinjury
Authors: A.K. Singh, V. Kumar, S.B. Rooge, A. Varshney, M. Vasudevan, A. Bhardhwaj, N. Trehanpati, R. Geffers, M.K. Sharma, S.K. Sarin
Journal: Journal of Hepatology (2017)
Population level outcomes and cost-effectiveness of expanding guidance for age-based hepatitis C testing in the United States
Authors: J.A. Barocas, A. Tasillo, G.E. Yazdi, J. Wang, C. Vellozzi, S. Hariri, C. Isenhour, L. Randall, J.A. Salomon, B.P. Linas
Journal: Journal of Hepatology (2017)
Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency
Authors: Marcia A. Munoz, Julie Jurczyluk, Sam Mehr, Ryan C. Chai, Rob J.W. Arts, Angela Sheu, Chelsea McMahon, Jacqueline R. Center, Davinder Singh-Grewal, Jeffrey Chaitow, Dianne E. Campbell, Julian M.W. Quinn, Kirill Alexandrov, Zakir Tnimov, Stuart G. Tangye, Anna Simon, Tri Giang Phan, Michael J. Rogers
Journal: Journal of Allergy and Clinical Immunology (2017)

Mevalonate kinase (MVK) deficiency (MKD) is a rare, autosomal-recessive autoinflammatory disease that presents in its milder form as hyper-IgD syndrome (HIDS), and in the most severe cases as mevalonic aciduria (MVA).1 It is widely assumed that the inflammatory symptoms of MKD are caused by defective protein prenylation owing to hypomorphic mutations in MVK. Prenylation is a posttranslational modification of proteins, particularly small GTPases, with isoprenoid lipids that are generated via the mevalonate biosynthetic pathway2 (Fig 1, A).
Multiple Comorbidities and Response to Cardiac Resynchronization Therapy
Authors: Emily P. Zeitler, Daniel J. Friedman, James P. Daubert, Sana M. Al-Khatib, Scott D. Solomon, Yitschak Biton, Scott McNitt, Wojciech Zareba, Arthur J. Moss, Valentina Kutyifa
Journal: Journal of the American College of Cardiology (2017)
Systems biology approach to identify processes and early markers for fibrosis in metabolically-induced non-alcoholic steatosis hepatitis in mice
Authors: A. Van Koppen, L. Verschuren, H. Nagabukuro, A. Costessi, M. Caspers, M. Morrison, K. Salic, R. Stoop, S.M. Turner, K. Li, C. Beysen, G. Hanauer, A.M. van den Hoek, R. Kleemann, R. Hanemaaijer
Journal: Journal of Hepatology (2017)
A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice
Authors: Andras Bilkei-Gorzo, Onder Albayram, Astrid Draffehn, Kerstin Michel, Anastasia Piyanova, Hannah Oppenheimer, Mona Dvir-Ginzberg, Ildiko Rácz, Thomas Ulas, Sophie Imbeault, Itai Bab, Joachim L Schultze, Andreas Zimmer
Journal: Nature Medicine (2017)
Treatment of severe forms of LPS-responsive beige-like anchor protein deficiency with allogeneic hematopoietic stem cell transplantation
Authors: Markus G. Seidel, Katrin Böhm, Figen Dogu, Austen Worth, Adrian Thrasher, Benoit Florkin, Aydan İkincioğulları, Anke Peters, Shahrzad Bakhtiar, Marie Meeths, Polina Stepensky, Isabelle Meyts, Svetlana O. Sharapova, Laura Gámez-Díaz, Lennart Hammarström, Stephan Ehl, Bodo Grimbacher, Andrew R. Gennery
Journal: Journal of Allergy and Clinical Immunology (2017)
Temporary suspension of sorafenib by adverse effects is associated with longer survival in patients with hepatocellular carcinoma
Authors: C. Rodríguez-Escaja, M.A. de Jorge Turrión, A.C. García, E.R. Díaz, M.L. González-Diéguez, C. Álvarez-Navascués, V. Cadahía-Rodrigo, M. Rodríguez, M. Varela
Journal: Journal of Hepatology (2017)
Efficacy and safety of Glecaprevir/Pibrentasvir in patients co-infected with hepatitis C virus and human immunodeficiency virus-1: the EXPEDITION-2 Study
Authors: J. Rockstroh, K. Lacombe, R.M. Viani, C. Orkin, D. Wyles, A. Luetkemeyer, R. Soto-Malave, R. Flisiak, S. Bhagani, K.E. Sherman, T. Shimonova, P. Ruane, J. Sasadeusz, J. Slim, Z. Zhang, T.I. Ng, R. Trinh, M. Sulkowski
Journal: Journal of Hepatology (2017)
A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis
Authors: Chaoshe Guo, Ye Sun, Bin Zhou, Rosalyn M. Adam, XiaoKun Li, William T. Pu, Bernice E. Morrow, Anne Moon, Xue Li
Journal: Journal of Clinical Investigation (2011)
Immunohistochemistry staining validation and prevalence of the estrogen receptor coactivator MED1 in primary and metastatic hormone receptor positive breast cancer.
Authors: Mahmoud Charif, Elyse E. Lower, Shagufta Khan, Diane Kennedy, Harriet Kumar, Jiang Wang, Xiaoting Zhang
Journal: Journal of Clinical Oncology (2015)

e11548 Background: MED1 is an estrogen receptor coactivator that is associated with resistance to antiestrogen therapy, and silencing MED1 sensitizes breast cancer cells to fulvestrant Cross talk between MED1 and HER-2 regulates tamoxifen resistance There is a need to standardize immunohistochemical (IHC) expression of MED1 in breast cancer and to determine the prevalence of overexpression in breast cancer Methods: This IRB approved study evaluated ER positive primary or metastatic breast cancers from patients treated at the University of Cincinnati Utilizing an antibody against the C-terminus of MED1, IHC was performed on paraffin embedded tissue All slides were evaluated by breast pathologist; and to establish inter-reader agreement, some specimens were read by two pathologists Nuclear staining was interpreted in a semi-quantitative modified Allred method. Proportion scores from 1 - 5 were assigned based on percentage of stained tumor cells as a continuous variable with cutpoints as follows: 0-5% (score 1), 6-25% (score 2), 26- 50% (score 3), 51-75% (score 4) and > 75% (score 5). Intensity of nuclear staining was assigned a score of 1-3, and an Expression Score was calculated by adding the proportion and intensity scores. Cytoplasmic staining was considered nonspecific Expression scores of > 4 were considered positive Inter-reader agreement was evaluated with kappa statistics with a p value < 0.05 considered significant Results: 108 specimens were stained and evaluated with 31 slides interpreted by two pathologists Most ER positive primary and metastatic breast cancer specimens overexpressed MED1 with 32 of 40 (80%) of primary and 49 of 68 (72%) metastatic breast cancer specimens were positive. There was good kappa agreement between the two independent pathologists with the kappa value 0.54, Fisher exact test p < 0.004. Conclusions: In this study we established a standard immunohistochemistry method for measuring MED1 expression in primary and metastatic human breast cancer tissue utilizing a composite score proportion and intensity of staining. MED1 was overexpressed in the majority of hormone dependent primary and metastatic breast cancers
Combined targeting of cholangiocytes and activated stromal cells with a BH3 mimetic ameliorates fibrosis in a mouse model of PSC
Authors: A. Moncsek, P.L. Splinter, S.P. O’Hara, C. Zuber, E. Patsenker, P. Valli, C.D. Fingas, A. Weber, B. Müllhaupt, N.F. LaRusso, J. Mertens
Journal: Journal of Hepatology (2017)
Validation of a simple scoring system to predict sorafenib effectiveness in patients with hepatocellular carcinoma
Authors: R. Tortora, A.C. Gardini, G. Cordone, G. Marisi, F.G. Foschi, M. Scartozzi, R. Granata, L. Faloppi, S. Cascinu, S. Nicola, O. Brunetti, V.O. Palmieri, G. Ercoloani, G.G. Di Costanzo
Journal: Journal of Hepatology (2017)
WTX101 in patients newly diagnosed with Wilson disease: final results of a global, prospective phase 2 trial
Authors: K.H. Weiss, F.K. Askari, P. Ferenci, A. Ala, A. Czlonkowska, D. Nicholl, J. Bronstein, D. Bega, M.L. Schilsky
Journal: Journal of Hepatology (2017)
Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations
Authors: William A. Beltran, Artur V. Cideciyan, Shannon E. Boye, Guo-Jie Ye, Simone Iwabe, Valerie L. Dufour, Luis Felipe Marinho, Malgorzata Swider, Mychajlo S. Kosyk, Jin Sha, Sanford L. Boye, James J. Peterson, C. Douglas Witherspoon, John J. Alexander, Gui-Shuang Ying, Mark S. Shearman, Jeffrey D. Chulay, William W. Hauswirth, Paul D. Gamlin, Samuel G. Jacobson, Gustavo D. Aguirre
Journal: Molecular Therapy (2017)

X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is an early onset and severe cause of blindness. Successful proof-of-concept studies in a canine model have recently shown that development of a corrective gene therapy for RPGR-XLRP may now be an attainable goal. In preparation for a future clinical trial, we have here optimized the therapeutic AAV vector construct by showing that GRK1 (rather than IRBP) is a more efficient promoter for targeting gene expression to both rods and cones in non-human primates. Two transgenes were used in RPGR mutant (XLPRA2) dogs under the control of the GRK1 promoter. First was the previously developed stabilized human RPGR (hRPGRstb). Second was a new full-length stabilized and codon-optimized human RPGR (hRPGRco). Long-term (>2 years) studies with an AAV2/5 vector carrying hRPGRstb under control of the GRK1 promoter showed rescue of rods and cones from degeneration and retention of vision. Shorter term (3 months) studies demonstrated comparable preservation of photoreceptors in canine eyes treated with an AAV2/5 vector carrying either transgene under the control of the GRK1 promoter. These results provide the critical molecular components (GRK1 promoter, hRPGRco transgene) to now construct a therapeutic viral vector optimized for RPGR-XLRP patients.
High Intratumoral Expression of Galectin-1 Correlates with Superior Outcome in HIV-Associated DLBCL
Authors: Maja Ludvigsen, Maja Ølholm Vase, Knud Bendix, Stephen Hamilton-Dutoit, Gabriel A Rabinovich, Michael Boe Moeller, Court Pedersen, Gitte Pedersen, Niels Obel, Carsten Schade Larsen, Francesco d'Amore
Journal: Blood (2016)
Abstract B25: Discovery of molecular probes inhibiting La:RNA interactions in cancer cells
Authors: Gunhild Sommer, Alena Fedarovich, Venkatesh Kota, Yuri K. Peterson, Tilman Heise
Journal: Cancer Research (2017)

Abstract The RNA-binding protein La is overexpressed in a number of tumor tissues and is proposed to support tumorigenesis via binding to mRNAs encoding tumor-promoting and anti-apoptotic factors to facilitate their translation. Our data suggest that those mRNAs might need La to be translated mainly in a cap-independent mechanism in cancer cells. Hence, small molecules able to block the binding of La to specific RNAs could represent a novel therapeutic strategy for cancer treatment. In an attempt toward this approach we developed a high-throughput fluorescence polarization assay to screen small compound libraries for molecules inhibiting the binding of La to an RNA element derived from cyclin D1 mRNA. Herein we describe a robust fluorescence polarization assay and the validation of primary hits by electrophoretic mobility shift assays. Using isothermal titration calorimetry we show that a compound binds to La and molecular modeling suggests an interaction between the compound and the RNA recognition motif of La. We have shown recently that La protects cells against cisplatin treatment by stimulating the protein synthesis of the anti-apoptotic factor Bcl2. Here we show by RNA immunoprecipitation experiments that one small compound specifically impairs the association of La with Bcl2 mRNA, reduces Bcl2 protein expression and sensitizes cells for cisplatin-induced cell death. Taken together, herein we report the development of a high-throughput fluorescence polarization assay to identify small compounds able to impair the binding of cancer-associated La to RNAs encoding tumor-promoting and anti-apoptotic factors in vitro and cancer cells. Citation Format: Gunhild Sommer, Alena Fedarovich, Venkatesh Kota, Yuri K. Peterson, Tilman Heise. Discovery of molecular probes inhibiting La:RNA interactions in cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B25.
Visualizing hepatocellular amino acid kinetics through mass spectrometry imaging of stable isotopes
Authors: M. Arts, Z. Soons, L.J. Dubois, K.A. Pierzchalski, S.R. Ellis, B. Balluff, G.B. Eijkel, T. Cramer, N. Lieuwes, S.M. Agten, T.M. Hackeng, L.J. van Loon, R.M. Heeren, S.W. Olde Damink
Journal: Journal of Hepatology (2017)
Evaluation of dosing strategy for pembrolizumab for oncology indications
Authors: Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H. Li, Rik de Greef, Dinesh de Alwis, Julie A. Stone
Journal: Journal for ImmunoTherapy of Cancer (2017)

Traditionally, most monoclonal antibodies (mAbs) have been dosed based on body weight because of perceived contribution of body size in pharmacokinetic variability. The same approach was used in the initial pembrolizumab studies; however, following availability of PK data, the need for weight-based dosing for pembrolizumab was reassessed.A previously established population PK (popPK) model as well as exposure-response results from patients with advanced melanoma or non-small cell lung cancer (NSCLC) were used to evaluate the potential application of a fixed dosing regimen with the aim of maintaining pembrolizumab exposures within the range demonstrated to provide near maximal efficacy and acceptable safety. Individual PK exposures for the selected fixed dosing regimen from recently completed trials with head and neck cancer, NSCLC, microsatellite instability high (MSI-H) in colorectal cancer (CRC) and urothelial cancer were used to confirm acceptability. To determine whether fixed dosing would maintain exposures within the range of clinical experience, the individual AUC distributions with fixed dosing were compared with the range of exposures from the pembrolizumab doses that were evaluated in early studies (2 mg/kg Q3W, 10 mg/kg Q3W/Q2W).Body-weight dependence of clearance was characterized by a power relationship with an exponent of 0.578, a value consistent with fixed- and weight-based dosing providing similar control of PK variability. A fixed dose of 200 mg Q3W was investigated in trials based on predicted exposures maintained within the established exposure range in all patients. Mean (% CV, n) AUCss, 6-weeks was 1.87 (37%, 830), 1.38 (38%, 760) and 7.63 (35%, 1405) mg*day/mL in patients receiving 200 mg, 2 mg/kg and 10 mg/kg Q3W pembrolizumab. High-weight patients had the lowest exposures with 200 mg Q3W; however, exposures in this group (>90 kg) were within the range of prior clinical experience at 2 mg/kg Q3W associated with near maximal efficacy.Doses of 200 mg and 2 mg/kg provide similar exposure distributions with no advantage to either dosing approach with respect to controlling PK variability. These findings suggest that weight-based and fixed-dose regimens are appropriate for pembrolizumab.
Serum Wisteria Floribunda agglutinin-positive sialylated mucin 1 as a biomarker of hepatic progenitor cell/biliary features in hepatocellular carcinoma and of recurrence after curative therapy
Authors: N. Tamaki, A. Kuno, A. Matsuda, H. Tsujikawa, K. Yamazaki, Y. Yasui, M. Mizokami, M. Kurosaki, M. Sakamoto, H. Narimatsu, N. Izumi
Journal: Journal of Hepatology (2017)
Frequency and causes of malnutrition in liver disease patients: results from a multi-centric cross-sectional survey from gastroenterology tertiary clinics
Authors: R. Vadan, S. Iacob, B. Stoica, S. Ichim, M. Lita, T. Manuc, C. Cijevschi, A. Trifan, D. Dobru, E. Dumitru, M. Tantau, C. Brisc, M. Diculescu, C. Gheorghe, L. Gheorghe
Journal: Journal of Hepatology (2017)
Patterns of chronic hand eczema: a semantic map analysis of the <scp>CARPE</scp> registry data
Authors: S. Cazzaniga, C. Apfelbacher, T. Diepgen, R.F. Ofenloch, E. Weisshaar, S. Molin, A. Bauer, V. Mahler, P. Elsner, J. Schmitt, B.K. Ballmer‐Weber, P. Spring, L. Naldi, L. Borradori, D. Simon
Journal: British Journal of Dermatology (2017)

Hand eczema has a high incidence and prevalence and has a negative impact on both physical and psychological well-being, with the risk of persistence as a chronic condition. Epidemiological studies on hand eczema provided mainly descriptive and risk analyses, but pattern analyses of variables associated with hand eczema, in particular chronic hand eczema, have not been explored to date.To investigate and display the semantics of associations between variables of hand eczema obtained from the Swiss and German registries of chronic hand eczema (CARPE) to dissect patterns and novel links.This was a cross-sectional study on selected variables from the CARPE registries. Associations between variables were analysed by means of an autoassociative system. A semantic connectivity map was generated by using a maximum spanning tree algorithm.Baseline datasets of 1466 patients with chronic hand eczema (Switzerland: 199; Germany: 1267) were analysed. Occupational exposure had the highest impact in the total and country cohorts. We identified two areas of exposure linked to corresponding occupations that clearly demarcated the sexes.This study, using semantic connectivity as a novel method of data analysis, reveals the complexity of features characterizing chronic hand eczema as well as novel association patterns that deserve further investigation.
New Lessons about Endometriosis — Somatic Mutations and Disease Heterogeneity
Authors: Grant W. Montgomery, Linda C. Giudice
Journal: New England Journal of Medicine (2017)

Endometriosis is a common estrogen-dependent inflammatory disorder that affects 6 to 10% of women of reproductive age and up to 50% of women with infertility and pelvic pain.1 Endometriosis is a complex disease with risk influenced by many factors; its pathogenesis is poorly understood, and current treatments have limitations.2 A role for genetics is well established, with approximately 50% of risk due to genetic factors and 50% due to environmental or other causes.3 The disease is heterogeneous, with multiple ectopic lesions containing endometrial-like tissue outside the uterus, primarily in the pelvic cavity.1 The lesions may be one of three types: . . .
Hepatitis E virus-specific T cell responses against non-structural viral proteins in patients with ongoing and resolved hepatitis E
Authors: J. Al-Ayoubi, P. Behrendt, B. Bremer, A. Gisa, F. Rinker, M.P. Manns, M. Cornberg, H. Wedemeyer, A.R.M. Kraft
Journal: Journal of Hepatology (2017)
IgG4 and IgG1 autoantibodies against Annexin A11 in IgG4-related disease of the biliary tract and pancreas
Authors: L. Hubers, H. Vos, A. Schuurman, R.O. Elferink, B. Burgering, S. van de Graaf, U. Beuers
Journal: Journal of Hepatology (2017)
Elucidation of non-alcoholic fatty liver disease immunopathogenesis in humanized mice
Authors: Z. Her, S.Y. Tan, M. Liu, X.Y. Chan, W.W.S. Tan, K.S.M. Yong, Z. Zheng, E. Loh, K.T.E. Chang, T.C. Tan, Q. Chen
Journal: Journal of Hepatology (2017)
Kangai 1 C-terminal interacting tetraspanin plays an important role in cholangiocarcinogenesis
Authors: K.C. Bui, M. Ly, T. Nguyen, S. Barat, X. Chen, P. Bozko, T.N. Linh, S.L. Huu, T.P. Velavan, P.G. Kremsner, B. Sipos, L. Wilkens, N.P. Malek, R.R. Plentz
Journal: Journal of Hepatology (2017)