tbuckley/cabot-search huggingface dataset:
HIV Coinfection Influences Natural Selection on Myobacterium tuberculosis
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2017)

a delightful cantata, "Sheep May Safely Graze," whose opening lyric boasts of shepherds protecting sheep from the ravages of the hunt.Fast forward a few centuries, where now, from a large genome study, a team of French and Argentinian scientists may have successfully identified the mutations behind the sheep traits that shepherds began saving from the huntfor their prized wool.Corresponding author Demars, from the
First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders (LTRs) in the LUX-Lung (LL) 3, 6 and 7 trials
Authors: M. Schuler, L. Paz-Ares, L.V. Sequist, Y.-L. Wu, S.L. Geater, A. Märten, J. Fan, K. Park, J.C.-H. Yang
Journal: Annals of Oncology (2017)
Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe
Authors: A.D. Marshall, S. Nielsen, E.B. Cunningham, A. Aghemo, H. Alho, M. Backmund, P. Bruggmann, O. Dalgard, R. Flisiak, G. Foster, L. Gheorghe, D. Goldberg, I. Goulis, M. Hickman, P. Hoffmann, L. Jancorienė, P. Jarčuška, M. Kåberg, M. Makara, M. Maimets, R. Marinho, M. Matičič, S. Norris, S. Olafsson, A. Øvrehus, J.-M. Pawlotsky, J. Pocock, G. Robaeys, C. Roncero, M. Simonova, J. Sperl, M. Tait, I. Tolmane, S. Tomaselli, M. van der Valk, A. Vince, G.J. Dore, J.V. Lazarus, J. Grebely
Journal: Journal of Hepatology (2017)
A 2-year multicenter, double-blind, randomized, placebo-controlled study of bezafibrate for the treatment of primary biliary cholangitis in patients with inadequate biochemical response to ursodeoxycholic acid therapy (Bezurso)
Authors: C. Corpechot, O. Chazouillères, A. Rousseau, D. Guyader, F. Habersetzer, P. Mathurin, O. Goria, P. Potier, A. Minello, C. Silvain, A. Abergel, M. Debette-Gratien, D. Larrey, O. Roux, J.-P. Bronowicki, J. Boursier, V. de Ledhingen, A. Heurgue-Berlot, E. Nguyen-Khac, F. Zoulim, I. Ollivier-Hourmand, J.-P. Zarski, G. Nkontchou, F. Gaouar, T. Simon, R. Poupon
Journal: Journal of Hepatology (2017)
Neutrophil dysfunction is potentially predictive of mortality and multi-organ failure in acute decompensation and acute-on-chronic liver failure patients
Authors: H. Lu, J. Macnaughtan, R. Sawhney, H. Jones, P. Holland-Fischer, M. Ghasemi, G. Wright, N. Davies, R.P. Mookerjee, R. Jalan
Journal: Journal of Hepatology (2017)
Trametinib for the Treatment of IGHV4-34, MAP2K1 Mutant Variant Hairy Cell Leukemia
Authors: Leslie A. Andritsos, Mirela Anghelina, Nicole R. Grieselhuber, Sameek Roychowdhury, Julie Reeser, Cynthia Timmers, Aharon G. Freud, James S. Blachly, David M. Lucas, Gerard Lozanski, Jeffrey Jones, Kerry A. Rogers, Weiqiang Zhao, Michael R. Grever
Journal: Blood (2016)
Evaluation of serum HBV RNA and HBcrAg in chronic hepatitis B patients achieving different serological outcomes on tenofovir disoproxil fumarate (TDF)
Authors: A.L. Cathcart, M. Buti, P. Marcellin, A. Gaggar, W. Delaney, K.M. Kitrinos, F. van Bömmel
Journal: Journal of Hepatology (2017)
Pain specialists call for annual review of long term opioid use
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Patients with chronic pain, especially those to whom long term opioids are prescribed in primary care, should undergo an annual review to ensure that drugs are not being prescribed inappropriately, specialist pain organisations believe.

Martin Johnson, chair of the Chronic Pain Policy Coalition and vice president of the British Pain Society, said that the two groups were pushing for there to be at least an annual review of patients with chronic pain, in the same way that patients with asthma are reviewed. They will be holding a meeting with stakeholders this summer to take the issue forward, to look at the …
The detection of clinically relevant cancer mutations using a high depth, augmented, comprehensive cancer gene panel.
Authors: Michael James Clark, Elena Helman, Sean Boyle, Shujun Luo, Deanna Church, Jason Harris, Mirian Karbelashvili, Stephen Chervitz, Parin Sripakdeevong, Gabor Bartha, Anil Jayant Patwardhan, John West, Richard Chen
Journal: Journal of Clinical Oncology (2015)

e12547 Background: Genetic testing is an increasingly accepted form of molecular testing in cancer. Specific genetic lesions can determine prognosis and have diagnostic value, assisting in therapeutic decisions. Next-generation sequencing facilitates the detection of a wide array of somatic mutations, copy number alterations (CNAs), and gene fusions all in a single assay. With increased sequencing depth, mutations present in only a fraction of the neoplastic tissue can be identified. Detection of these mutations after sequencing DNA and RNA involves a complex set of variant detection algorithms tailored specifically for cancer analysis. Methods: We designed a comprehensive cancer panel using an augmented target enrichment strategy optimized for even coverage across the entire span of gene content. This approach includes multiple nucleic acid enrichments to deal with high-GC content and includes custom oligonucleotides designed to compensate for challenging regions. The panel includes over 1,200 cancer-relevant genes and over 300 cancer-relevant micro-RNAs. Samples enriched through this method are sequenced to very high depth ( > 500x) to facilitate detection of low representation alleles. To detect small variants, CNAs, and gene fusions, we developed a bioinformatics pipeline. We tested the panel and pipeline using over 30 different cancer samples including over 20 cancer cell lines, engineered cells containing specific cancer mutations, and primary tumors in FFPE. Results: We demonstrate that this cancer gene panel and analysis strategy is able to detect mutations of each major type with high sensitivity and positive predictive value. We saw greater than 99% sensitivity for small variants down to 5% allele frequency. We also detected known gene fusion events including EML4-ALK and BCR-ABL1 accurately in all 20 cancer samples with known fusions. Moreover, the assay was able to identify CNAs consistent with the known state, including detection of EGFR amplification, EGFRvIII, PTEN loss, and p16 loss in known cases. Conclusions: The high depth, augmented cancer gene panel assay is able to comprehensively identify cancer mutations with high accuracy.
The advantages of using non-HDL-C in the diagnosis and treatment of dyslipidemia [10] (multiple letters)
Authors: Carlos A. Aguilar-Salinas, Adriano Delgado, Francisco J. Gómez-Pérez, Yadong Cui, Roger S. Blumenthal, Maura K. Whiteman, Jodi A. Flaws
Journal: JAMA Internal Medicine (2002)
Reply to Tuomas Mirtti and Tero Aittokallio's Letter to the Editor re: Fatemeh Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, et al. How Reliable are Trial-based Prognostic Models in Real-world Patients with Metastatic Castration-resistant Prostate Cancer? Eur Urol. 2017;71:838–40. Clinical Utility of Trial-estimated Prognostic Models
Authors: Fatemeh Seyednasrollah, Mehrad Mahmoudian, Liisa Rautakorpi, Outi Hirvonen, Tarja Laitinen, Sirkku Jyrkkiö, Laura L. Elo
Journal: European Urology (2017)
Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study
Authors: Vladimir Koblizek, Branislava Milenkovic, Adam Barczyk, Ruzena Tkacova, Attila Somfay, Kirill Zykov, Neven Tudoric, Kosta Kostov, Zuzana Zbozinkova, Jan Svancara, Jurij Sorli, Alvils Krams, Marc Miravitlles, Arschang Valipour
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.
Abstract 280: Deficiency of FKBP12 in the Heart Leads to Impaired Contractility and Pregnancy Induced Cardiomyopathy
Authors: Joshua Oakes, Susan Hamilton
Journal: Circulation Research (2013)

FK506 Binding Proteins (FKBPs) are a family of cis-trans prolyl isomerases that bind rapamycin and FK506. FKBP12 and 12.6 interact with ryanodine receptors (RyR), homotetrameric transmembrane ion channels that regulate Ca2+ release from the sarcoplasmic reticulum (SR). FKBP12 interacts with RyR1 in skeletal muscle and FKBP12.6 interacts with RyR2 in cardiac muscle to regulate the Ca2+ leak properties of these channels. Recently it has been suggested that FKBP12 also plays a role in regulating RyR2 activity. Using mice with a cardiac specific deficiency in FKBP12, we analyzed the role of FKBP12 in cardiac function. We found that both male and female mice with a α-MyHC Cre/Lox mediated deficiency in FKBP12 in the heart (FKBP12 KD) developed a mild dilated cardiomyopathy, with enlarged left ventricular diameter both during systole and diastole, decreased ejection fraction and decreased fractional shortening. To elucidate the mechanism for these effects we assessed Ca2+ sparks in isolated cardiomyocytes. We found an increase in both Ca2+ spark frequency and spark amplitude in FKBP12 cardiac deficient mice without a change in spark duration. Despite a mild phenotype in adult mice, we found that approximately 25% of all pregnancies (26/106) in the FKBP12 deficient mice resulted in the mothers dying following the birth. Autopsies show that these cardiac specific FKBP12 deficient mice had increased heart weight and significantly dilated ventricles compared to female Cre mice. Our data suggest that a cardiac specific deficiency in FKBP12 leads to the development of pregnancy induced cardiomyopathy. Echocardiography on FKBP12 deficient mice one day after giving birth found that there was no significant difference in ejection fraction or fractional shortening compared to α-MyHC Cre control mice. FKBP12 deficient females, however, had larger hearts and 50% (2/4) displayed heart failure and died. In conclusion, we show that FKBP12 does indeed alter Ca2+ handling in the heart and that a loss of FKBP12 leads to the development of pregnancy induced cardiomyopathies in females.
Recommendation to test limonene hydroperoxides 0·3% and linalool hydroperoxides 1·0% in the British baseline patch test series
Authors: C. Wlodek, C.M. Penfold, J.F. Bourke, M.M.U. Chowdhury, S.M. Cooper, S. Ghaffar, C. Green, C.R. Holden, G.A. Johnston, A.A. Mughal, C. Reckling, R.A. Sabroe, N.M. Stone, D. Thompson, S.M. Wilkinson, D.A. Buckley
Journal: British Journal of Dermatology (2017)

Background There is a significant rate of sensitization worldwide to the oxidized fragrance terpenes limonene and linalool. Patch testing to oxidized terpenes is not routinely carried out; the ideal patch test concentration is unknown. Objectives To determine the best test concentrations for limonene and linalool hydroperoxides, added to the British baseline patch test series, to optimize detection of true allergy and to minimize irritant reactions. Methods During 2013–2014, 4563 consecutive patients in 12 U.K. centres were tested to hydroperoxides of limonene in petrolatum (pet.) 0·3%, 0·2% and 0·1%, and hydroperoxides of linalool 1·0%, 0·5% and 0·25% pet. Irritant reactions were recorded separately from doubtful reactions. Concomitant reactions to other fragrance markers and clinical relevance were documented. Results Limonene hydroperoxide 0·3% gave positive reactions in 241 (5·3%) patients, irritant reactions in 93 (2·0%) and doubtful reactions in 110 (2·4%). Linalool hydroperoxide 1·0% gave positive reactions in 352 (7·7%), irritant reactions in 178 (3·9%) and doubtful reactions in 132 (2·9%). A total of 119 patients with crescendo reactions to 0·3% limonene would have been missed if only tested with 0·1% and 131 patients with crescendo reactions to 1·0% linalool would have been missed if only tested with 0·25%. In almost two‐thirds of patients with positive patch tests to limonene and linalool the reaction was clinically relevant. The majority of patients did not react to any fragrance marker in the baseline series. Conclusions We recommend that limonene hydroperoxides be tested at 0·3% and linalool hydroperoxides at 1·0% in the British baseline patch test series.
シロリムス溶出性ステント(SES)を用いた経皮的冠インターベンションを受けた患者の長期転帰に対する非HDLコレステロールの影響
Authors: Higashikata Toshinori, Kaneda Tomoya, Takata Mutsuko, Yamamoto Ryusuke, Ohira Miho, Ueda Kosei
Journal: Circulation (2014)
Do patients need lifelong follow-up? Why?
Authors: Rahul Gosain, Shruti Bhandari, Amitoj Singh Gill, Mesgana Befikadu, Joseph Abraham, Stefan Terwindt, Robert Paul Stephan, Kenneth David Miller
Journal: Journal of Clinical Oncology (2014)

e20600 Background: Patterns of long-term follow-up care for patients treated for cancer are not well characterized. Anecdotally, many oncologists indicate that they recommend lifelong follow-up, though the reasons for follow-up and expected outcomes are not clear. The purpose of this pilot study was to determine oncologists’ perceptions of their patients’ residual risk of recurrence as well as the duration and reasons for follow-up care. Methods: A survey was designed in collaboration with MDoutlook and sent to a group of medical oncologists. Questions included demographics, medical training, practice setting, and oncology sub-specialization. Participants were asked for their recommended follow-up care, and its purpose, and their perceived “residual risk” of recurrence for their patients. Results: Of 93 medical oncologists who responded, 61% were male and 39% female, with a median of 24.5 years of practice post-training (Range:2-49). Among this sample of oncologists, recommended duration of follow up care varied by cancer type (see table 1). At 5, 10, and 15 years, the two most common reasons for follow up were screening for late and long-term effects followed by screening for new cancer while at 20 years, these were screening for late and long-term effects, followed by the patient’s peace of mind. 48%, 62% and 64% of oncologists reported that less ≤10% of patients returned with secondary cancer, second cancer, and late and long term effects, respectively. For patients with colon, lung, lymphoma and breast cancer, 77%, 68%, 61% and 50% of oncologists respectively perceived their patients’ “residual risk” of recurrence was essentially zero at 20+ years. Conclusions: Lifelong follow up is frequently recommended though the perceived risk of recurrence, late and long term effects and risk of second cancer are low. Long-term follow-up guidelines may help optimize the impact of these visits. Length of follow-up care recommended by cancer type (% of oncologists). Years of follow-up Breast cancer Colon cancer Lung cancer Large Cell Lymphoma Acute Leukemia Prostate cancer Testicular cancer 5 25.5 53.4 43 37.3 26 29.2 35.6 10 23.9 15.5 19 23.7 19.5 25 23.7 15 2.8 1.7 0 0 0 2.1 1.7 20 4.2 1.7 3.5 1.7 2.2 4.2 3.4 Lifelong 43.6 27.6 34.5 37.3 52.3 39.5 35.6
Treatment outcomes of hepatitis C virus recombinant form 2k/1b with sofosbuvir based regimens in Georgia
Authors: M. Zakalashvili, J. Zarkua, M. Weizenegger, J. Bartel, M. Raabe, T. Telia, M. Zhamutashvili, S. Metreveli, M. Barnova, N. Abramishvili, R. Gish, I. Rtskhiladze, D. Metreveli
Journal: Journal of Hepatology (2017)
Prevalence and prognostic importance of precipitating factors leading to heart failure hospitalization: recurrent hospitalizations and mortality
Authors: Elke Platz, Pardeep S. Jhund, Brian L. Claggett, Marc A. Pfeffer, Karl Swedberg, Christopher B. Granger, Salim Yusuf, Scott D. Solomon, John J. McMurray
Journal: European Journal of Heart Failure (2017)
Genetic differences in hepatocellular carcinoma among chronic persistent hepatitis B virus infection with or without viral suppression and prior hepatitis B virus infection
Authors: F. Kawai-Kitahata, Y. Asahina, S. Kakinuma, M. Murakawa, S. Nitta, H. Nagata, S. Kaneko, S. Otani, Y. Asano, E. Inoue, M. Miyoshi, T. Tsunoda, A. Sato, M. Nakagawa, Y. Itsui, S. Azuma, S. Tanaka, M. Tanabe, S. Maekawa, N. Enomoto, M. Watanabe
Journal: Journal of Hepatology (2017)
INTRAVASCULAR ULTRASOUND ASSESSMENT OF MINIMAL STENT AREA AND INTIMAL HYPERPLASIA IN IN–STENT RESTENOSIS AFTER DRUG–ELUTING OR BARE–METAL STENT IMPLANTATION: THE NORDIC INTRAVASCULAR ULTRASOUND STUDY (NIVUS)
Authors: Lisette Okkels Jensen, Saila Vikman, Lisbeth Antonsen, Matti Niemela, Kari Kervinen, Andrejs Erglis, Jan Harnek, Per Thayssen, Leif Thuesen, Kari Niemela
Journal: Journal of the American College of Cardiology (2013)
Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate (Annals of Internal Medicine (2006) 145, (247-254))
Authors: A. S. Levey, J. Coresh, T. Greene, L. A. Stevens, Y. Zhang, S. Hendriksen
Journal: Annals of Internal Medicine (2008)
Heart radiation dose as a risk factor for dyspnea worsening after multimodality treatment for non-small cell lung cancer and pleural mesothelioma: An exploratory analysis
Authors: A. Botticella, C. Billiet, G. Defraene, C. Draulans, K. Nackaerts, C. Deroose, J. Coolen, P. Nafteux, D. De Ruysscher
Journal: Annals of Oncology (2017)
Bile duct strictures after liver transplantation are associated with a donor glypican-6 polymorphism linked to the biliary stem cell niche
Authors: J.W. Selten, F.J. Roos, C.J. Verhoeven, H.J. Metselaar, J.N. IJzermans, L.J. van der Laan
Journal: Journal of Hepatology (2017)
A study of Ki-67 labeling index in invasive nonmetastatic breast carcinoma.
Authors: Priyanka Srivastava, Rakesh Chopra
Journal: Journal of Clinical Oncology (2014)

e14001 Background: This study evaluates the predictive value of Ki-67 in patients with invasive breast cancer receiving neoadjuvant chemotherapy (NACT) and its correlation with established prognostic factors. Methods: This is a prospective observational study of 165 invasive nonmetastatic breast cancer patients. Clinicopathological characteristics and Ki-67 labeling index were assessed. Patients with locally advanced breast carcinoma (LABC) received NACT and response rates were evaluated. Statistical significance was calculated using Chi Square test, unpaired t test, and non-parametric Mann-Whitney test. Results: Amongst the Ki-67 high group a significantly large majority of patients had grade 3 tumor (86.8% vs. 13.1%, p value < 0.001), ER negativity (56.8% vs. 11.4% p value < 0.001), PR negativity (65.3% vs. 18.6%, p value < 0.001), HER2/neu overexpression (47.4 % vs11.4 % , p value < 0.001) and lymphovascular invasion (LVI) (29.4% vs. 14.7% p value= 0.024). In high Ki-67 group 24.3% achieved CR compared to 6.2% in low Ki-67 group, (p value =0.012). A higher percentage of patient-achieved PR in high Ki-67 group than low Ki-67 group (68.3% vs. 50%, p value = 0.017). Conclusions: High Ki-67 correlates with poor prognostic factors including hormone negativity, HER 2 neu positivity, and grade III tumors and LVI. High Ki 67 labeling index is a predictive marker for the response to NACT in LABC patients. Ki-67 low- number (%) Ki-67 high - number (%) P value Total patients 70 (42.4%) 95 (57.6%) - T1/T2/T3 19(27.1%)/31(44.3%)/6(8.6%) 22(23.2%)/42(44.2%)/8(8.4%) NS T4b/T4d 12(17.1%)/1(1.4%) 22(23.2%)/1(1.1%) NS Node positive 37(52.9%) 59(62.15%) NS Grade 3 5(13.1%) 33(86.8%) <0.001 Mitotic index (>20/hpf) 4(5.8%) 34(40%) <0.001 ER positive 62(88.6%) 41(43.2%) <0.001 PR positive 57(81.4%) 33(34.7%) <0.001 HER2/neu positive 8(11.4%) 45(47.4%) <0.001 Basal type 2(2.8%) 30(31.5%) - Patients receiving NACT (total no.- 57) 16(28%) 41(71.9%) - Complete response 1(6.2%) 10(24.3%) 0.012 Partial response 8(50%) 28(68.3%) 0.017 Overall response rate 9(56.2%) 38(92.68%) <0.001
Prognostic value of pretreatment neutrophil lymphocyte ratio in metastatic breast cancer.
Authors: Aicha Mazouz, Chad Mohamed Amine, Lamiae Boudahna, Nadia Benaicha, Chakib Nejjari, Samia Arifi, Nawfel Mellas
Journal: Journal of Clinical Oncology (2015)

e11500 Background: The neutrophil-lymphocyte ratio (NLR) has been reported to reflect systemic inflammation and to have independent prognostic value for patients with various cancers. Here, we analyzed the prognostic significance of the pretreatment NLR in metastatic breast cancer (MBC). Methods: Data from 200 MBC patients diagnosed between January 2009 and December 2013 in our department were evaluated retrospectively. The pretreatment NLR was defined as the neutrophil count divided by lymphocyte count and NLR cut-off values of ≥ 2.5 and < 2.5 were used according to previous studies. Kaplan Meier method was used to analyze survival according to NLR level. Cox hazard model was performed for adjusting in confounding factors. Significance level was p ≤ 0.05. Results: The average age was 48 years-old [23-84]. The breast cancer was ductal histologic and undifferentiated type in 94% and 40% of cases respectively. The expression of hormonal receptor was noted in 71% of cases. The human epidermal growth factor-2 was over expressed in 20% of cases. The disease was metastatic at diagnosis in 70% of cases. The most common sites of metastasis were the bone, lung, liver, pleura and brain respectively. 40% of patients had a higher pretreatment NLR. The chemotherapy was given as a first line in 80%of cases. Trastuzumab was given in 15% of cases. The objective response rate was 67%. After a median follow up of 19 months, the median of progression free survival (PFS) and overall survival (OS) were 10 months and 20 months respectively. In the univariate analysis, an increased pretreatment NLR was significantly associated with shorter OS with p = 0.06 such as, recurrent disease, multi-organ involvement and metastasis to viscera with respectively p = 0.04, p = 0.02 and p < 0.01. In the multivariate analysis, we identified an increased pretreatment NLR as in independent predictor for OS with HR = 1.7-95% CI = [1.02-2.83] and p = 0.04 such as metastasis to viscera with HR = 3-95% CI = [1.36-6.69] and p = 0.07. Conclusions: Pretreatment NLR may be an independent prognostic factor in MBC with shorter OS. This combined index should be considered as a potential prognostic biomarker in future.