tbuckley/cabot-search huggingface dataset:
Periodic measurement of N-telopeptides of type I collogen in serum (sNTx) for early diagnosis of bone metastasis in patients with lung cancer.
Authors: Koji Takeda, Shinya Tokunaga, Haruko Daga, Hideaki Okada, Koichi Taira, Natsuko Miyamoto, Michiyo Hattori, Motohiro Tamiya, Masashi Kobayashi, Norio Okamoto, Shinji Sasada, Hidekazu Suzuki, Naoko Morishita, Yuka Matsuura, Tomonori Hirashima
Journal: Journal of Clinical Oncology (2012)

e18042 Background: The bone resorption biomarker sNTx has been previously shown to add value as an aid in the diagnosis of bone metastasis in patients with lung cancer. The objective of this prospective study was to determine if periodic sNTx measurements could lead to early diagnosis of bone metastasis in patients with lung cancer. Methods: Patients with newly diagnosed organ-confined lung cancer were enrolled. sNTx values were determined once each month using the OSTEOMARK TM serum NTx assay (Alere Medical). The presence or absence of bone metastasis was determined by monthly physical examination and by bone scintigraphy every 3 months for 12 months. All patients were required to provide written informed consent. Results: Forty patients were enrolled between June and December 2010. One patient withdrew early and was excluded from analysis. The mean +/- 1 SD baseline level of sNTx was 17.5 +/- 4.4 nM BCE/L. Five patients developed bone metastasis (as characterized by bone scintigraphy) during the study period. The level of sNTx in subjects with bone metastasis was slightly increased (21.6 +/- 3.2 nM BCE/L), however, in these patients, there was no statistically significant difference between sNTx values at baseline (18.2 +/- 4.2 nM BCE/L) and when metastasis was diagnosed. (p=0.176). When a cut-off value of sNTx was set to 22.0 nM BCE/L, the sensitivity and the specificity of detection of bone metastasis were 80.0% and 41.2%, respectively. Using this cut-off, the elevation of sNTx could predict bone metastasis at least one month before diagnosis by bone scintigraphy in all 5 patients, however, the specificity was relatively low for clinical implementation. Additionally, the sensitivity and the specificity of early detection of systematic spread of disease (including bone metastasis) were 70.6% and 45.5%, respectively. Conclusions: Periodic determination of sNTx in patients with organ confined lung cancer did not provide sufficient specificity for it to be used for the early diagnosis of bone metastasis or disease progression.
A man with chest tightness and burning limbs
Authors: Zhong Yi, Yen Shu Huang, Lei Wang, Yun-Tao Zhao
Journal: BMJ (2017)

A 73 year old man arrived at the cardiac clinic complaining of chest tightness when walking or speaking loudly. He had oedema in both legs and intermittent burning pain in his abdomen and extremities, especially the forearms and ankles, which had persisted for one month. He had no history of diabetes mellitus, rheumatic disease, or cerebral haemorrhage, and his vital signs were normal. Physical examination revealed acrocyanosis and hyperpigmentation on his abdomen, and tenderness to palpation across his entire chest area. He showed no jugular venous distention or pulmonary rales.

The patient had 

An echocardiogram showed a bi-atrial enlargement (left atrium, 58×51 mm; right atrium, 53×43 mm) and left ventricular concentric hypertrophy (ventricular septum thickness, 14 mm; posterior wall thickness, 14 mm). The left ventricular ejection fraction was 65%. Cardiac magnetic resonance imaging (MRI) showed concentric thickening of the left ventricular wall and global transmural late gadolinium enhancement.

1.  What is the most likely diagnosis?

2.  What steps can physicians take to confirm the most likely diagnosis?

3.  How would you manage this patient?

### 1. What is the most likely diagnosis?

#### Short answer

Cardiac amyloidosis. …
Effect of a multispecies probiotic mixture on cognitive function, risk of falls and inflammatory response in patients with cirrhosis
Authors: E. Román, J.C. Nieto, C. Gely, S. Vidal, M. Pozuelo, M. Poca, C. Juárez, C. Guarner, C. Manichanh, G. Soriano
Journal: Journal of Hepatology (2017)
The impact of multidisciplinary support to alcohol misusers at risk of alcohol relapse after liver transplantation
Authors: B. Lattanzi, R. Ledda, V. Di Gregorio, A.M. Galli, G. Mennini, D. D’Ambrosio, M. Rossi, S.G. Corradini, M.L. Attilia, M. Merli
Journal: Journal of Hepatology (2017)
Phase I study of ganetespib (G), capecitabine (C), and radiation (RT) in rectal cancer.
Authors: Bassel F. El-Rayes, Charles A. Staley, Roberto Diaz, Patrick S. Sullivan, Walid Labib Shaib, Jerome Carl Landry
Journal: Journal of Clinical Oncology (2015)

3596 Background: Ganetespib (G) is a heat shock protein 90 inhibitor . Preclinical data show that G is a potent radiosensitizer for rectal cancer. The aim of this study is to determine the recommended phase II dose of G when combined with capecitabine (C) and radiation (RT) in resectable rectal cancer. Methods: Patients (pts) with stage II or III rectal adenocarcinoma with distal border within 12 cm of anal verge, no prior therapy, and adequate organ functions, were eligible. A 3+3 dose escalation design was used. Pts received 2 weeks of G at 150 mg/m2 I.V. on days -14, -11, -7, and -4. Pre and post-treatment tumor biopsies were obtained. C (825 mg/m2) and RT (50.4Gy) were administered 5 days per week for 5.5 to 6 weeks starting day 1. G was administered on days 1, 8, 15, 29 and 36. G dose levels were 60, 80, 100, and 120 mg/m2. Pharmacokinetic sampling for C and G were performed on days 1, 2, 15, and 16. Dose limiting toxicities (DLT) were defined as the occurrence of any treatment related: grade (gr) 4 hematologic or gr 3 or higher non-hematologic toxicities, gr 3 nausea, vomiting or diarrhea lasting > 4 days, any interruption of RT > 10 days, more than 2 interruptions in RT, delay in completion of RT for > 14 days, or inability to deliver more than 85% of planned RT dose. Results: 16 pts were enrolled in the study; 1 pt received only day-14 and was not .evaluable for toxicity. Evaluable pts had a median age of 61 yrs, 7 females, and endoscopic stage: T3N0 (6 pts), T3N1 (6), T3N2 (2), T4N1 (1); 3 pts were treated on each dose level, 2 pts on dose level 4 required dose reduction, so we enrolled 3 additional pts on level 3 (100 mg/m2). One DLT was observed (gr 3 diarrhea for more than 4 days). Other toxicities on the study were: diarrhea gr 3 (3 pts), gr 2 (6), gr 1 (2), radiation dermatitis gr 2 (9), gr 1 (3), fatigue gr 2 (5), gr 1 (4), hand foot syndrome gr 2 (1), mucositis gr 1 (2), and nausea/vomiting gr 2 (2), gr 1 (8). 12 pts have completed surgical resection (2 APR and 10 LAR). Pathologic complete response (pCR) rate was 25% (3/12) and 2 pts had residual tumors less than 1 cm (pT1N0). Six of 9 (67%) pts had clearing of lymph nodes disease on pathologic specimen. Conclusions: G can be safely combined with standard C and RT in the neoadjuvant setting in rectal cancer. Preliminary data on activity appear promising. Clinical trial information: 01554969.
LUX-Lung 8 phase III trial: Analysis of long-term response to second-line afatinib in patients with advanced squamous cell carcinoma (SCC) of the lung
Authors: J.C.-H. Yang, G. Goss, E. Felip, S. Lu, A. Ardizzoni, S.M. Gadgeel, V. Georgoulias, N. Dupuis, E. Ehrnrooth, J.-C. Soria
Journal: Annals of Oncology (2017)
Population Genomics Reveals Speciation and Introgression between Brown Norway Rats and Their Sibling Species
Authors: Huajing Teng, Yaohua Zhang, Chengmin Shi, Fengbiao Mao, Wanshi Cai, Liang Lu, Fangqing Zhao, Zhongsheng Sun, Jianxu Zhang
Journal: Molecular Biology and Evolution (2017)

Murine rodents are excellent models for study of adaptive radiations and speciation. Brown Norway rats (Rattus norvegicus) are successful global colonizers and the contributions of their domesticated laboratory strains to biomedical research are well established. To identify nucleotide-based speciation timing of the rat and genomic information contributing to its colonization capabilities, we analyzed 51 whole-genome sequences of wild-derived Brown Norway rats and their sibling species, R. nitidus, and identified over 20 million genetic variants in the wild Brown Norway rats that were absent in the laboratory strains, which substantially expand the reservoir of rat genetic diversity. We showed that divergence of the rat and its siblings coincided with drastic climatic changes that occurred during the Middle Pleistocene. Further, we revealed that there was a geographically widespread influx of genes between Brown Norway rats and the sibling species following the divergence, resulting in numerous introgressed regions in the genomes of admixed Brown Norway rats. Intriguing, genes related to chemical communications among these introgressed regions appeared to contribute to the population-specific adaptations of the admixed Brown Norway rats. Our data reveals evolutionary history of the Brown Norway rat, and offers new insights into the role of climatic changes in speciation of animals and the effect of interspecies introgression on animal adaptation.
Targeted therapies in the treatment of advanced pancreatic adenocarcinoma (PC): A systematic review and meta-analysis of randomized trials.
Authors: Venessa T. Chin, Adnan Nagrial, Lorraine A. Chantrill, Katrin Marie Sjoquist, Chelsie O'Connor, Marina Pajic, Andrew Victor Biankin, Desmond Yip
Journal: Journal of Clinical Oncology (2014)

e15209 Background: PC has a uniformly poor prognosis and has marked genetic heterogeneity. Although some progress has been made recently in the treatment for advanced disease, the role of targeted therapy (TT) remains controversial. We aimed to better define the role of TTs in PC by performing a systematic review and meta-analysis of relevant randomised controlled trials (RCT). Methods: RCTs with at least one treatment arm containing a TT were identified from systematically searching databases (MEDLINE, EMBASE, CENTRAL) and conference abstracts from Jan 1996 - Dec 2013. We considered monoclonal antibodies or small molecules against specific receptors or signaling pathways as TTs. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), response rates (RR), adverse events (AE) and quality of life (QOL). Hazard ratios (HR), confidence intervals (CI) and p-values were analysed using a fixed effects model with Revman 5.2. Results: 23 trials with a total of 6,972 patients were identified, (12 phase II, 11 phase III) 23 with OS data, 20 with PFS data. TT prolonged PFS (HR 0.90 [0.85, 0.95] p=0.0001) but not OS (HR 0.97 [0.92, 1.03], p=0.31). QOL was assessed in 10 trials but results were inconsistent. AEs were assessable in 21 trials with the majority (13/21) showing increased toxicity with TTs. Conclusions: TTs potentially offer a small benefit in PFS, but not OS. PC is increasingly recognised as molecularly heterogeneous and by selecting a patient population most likely to benefit based on molecular profile, the magnitude of improvement may be increased. Future studies of TT stratified by molecular profile should be explored.
Baseline neutrophil to lymphocyte ratio can identify favourable corticosteroid response in alcoholic hepatitis
Authors: E. Forrest, N. Storey, S. Rohit, D. Shawcross, A. McCune, D. Gleeson, S. Hood, M. Wright, J. Dillon, A. Fraser, D. Patch, P. Richardson, S. Masson, A. Austin, J. Ryan, S. Atkinson, S. Ryder, M. Thursz, M. Allison, P. Hayes
Journal: Journal of Hepatology (2017)
Clinical significance of urinary neutrophil gelatinase-associated lipocalin measurement in differentiating various etiologies of acute kidney injury in cirrhotic patients
Authors: E.L. Yoon, J.H. Lee, S.E. Park, M. Kim, T. Kim, J.Y. Park, J.M. Choi, T.J. Jeon, W.C. Shin, W.-C. Choi
Journal: Journal of Hepatology (2017)
Abstract 10270: Increased Circulating Myostatin is Predictive of Mortality in Congestive Heart Failure.
Authors: Damien Gruson, Thibault Lepoutre, Sylvie A Ahn, Jean Cumps, Jean-Marie Ketelslegers, Michel F Rousseau
Journal: Circulation (2011)

Background: Myostatin (Mstn), a member of transforming growth factor beta (TGF-s) family, regulating skeletal muscle mass, is emerging as a regulator of cardiomyocytes trophicity. Recent observatio...
Impact of hepatoprotective medications on the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin in hepatitis C virus genotype lb-infected Asian patients with and without cirrhosis in the ONYX-I and -II studies
Authors: W.-L. Chuang, Y. Luo, J. Heo, G.-Q. Wang, M.-L. Yu, Y.J. Kim, Q. Xie, C.-Y. Peng, M. Zhang, Y. Huang, W. Lu, L.M. Fredrick, N. Mobashery, L. Wei
Journal: Journal of Hepatology (2017)
Abstract IA03: mTORC1/S6K1: Regulation of RNA biogenesis, protein synthesis, and cell metabolism
Authors: John Blenis, Gina Lee, Jamie Dempsey, Christina England
Journal: Cancer Research (2017)

Abstract The mTOR Complex 1 (mTORC1) signaling pathway has evolved to sense and respond to cellular energy status, nutrient availability and surrounding oxygen concentrations. In addition, mTORC1 signaling can be further activated by mitogen- and hormone-stimulated kinases including Akt, ERK and RSK, and suppressed by mTORC1 and its effector S6K1, via a variety of negative feedback loops. This incredible integration of extracellular and intracellular cues translates into carefully regulated outputs that control cell growth, motility and survival. A major mechanism through which mTOR regulates downstream processes is via the regulation of gene expression, mRNA processing, protein synthesis and protein degradation. In an mTOR phosphoproteomic screen, we and others identified SR Protein Kinase 2 (SRPK2) as a potential downstream effector of mTORC1. I will discuss a novel mechanism by which SRPK2 is regulated and contributes to mTORC1-dependent regulation of lipid metabolism via the regulation of mRNA processing. Citation Format: John Blenis, Gina Lee, Jamie Dempsey, Christina England. mTORC1/S6K1: Regulation of RNA biogenesis, protein synthesis, and cell metabolism. [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 IA03.
Implications of Unc5A depletion for hepatocyte survival in chronic liver diseases upon induction of the unfolded protein response
Authors: R. Barnault, M.-L. Plissonnier, T. Lahlali, M. Michelet, N. Laverdure, B. Ducarouge, F. Zoulim, P. Mehlen, R. Parent
Journal: Journal of Hepatology (2017)
Preoperative von willebrand factor – antigen predicts clinical outcome after liver resection: a prospective, international, multicenter trial
Authors: P. Starlinger, S. Haegele, P. Braeuer, L. Oehlberger, F. Primavesi, A. Kohler, F. Offensperger, D. Pereyra, A. Ferlitsch, G. Beldi, S. Staettner, C. Brostjan, T. Gruenberger
Journal: Journal of Hepatology (2017)
Hepatitis C virus hepatitis B virus co-Infection disproportionately worsens cirrhosis, hepatic decompensation, and hepatocellular carcinoma incidence in Non-Asians as compared to Asians
Authors: M. Joseph-Talreja, P. Nguyen, C. Zhao, A.K. Le, J. Hoang, L.A. Yasukawa, S.C. Weber, M.H. Nguyen
Journal: Journal of Hepatology (2017)
Neutrophil-derived S100 calcium-binding proteins A8/A9 promote reticulated thrombocytosis and atherogenesis in diabetes
Authors: Michael J. Kraakman, Man K.S. Lee, Annas Al-Sharea, Dragana Dragoljevic, Tessa J. Barrett, Emilie Montenont, Debapriya Basu, Sarah Heywood, Helene L. Kammoun, Michelle Flynn, Alexandra Whillas, Nordin M.J. Hanssen, Mark A. Febbraio, Erik Westein, Edward A. Fisher, Jaye Chin-Dusting, Mark E. Cooper, Jeffrey S. Berger, Ira J. Goldberg, Prabhakara R. Nagareddy, Andrew J. Murphy
Journal: Journal of Clinical Investigation (2017)

Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis. IL-6 acts on hepatocytes to enhance the production of thrombopoietin, which in turn interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow progenitor cells to promote their expansion and proliferation, resulting in reticulated thrombocytosis. Lowering blood glucose using a sodium-glucose cotransporter 2 inhibitor (dapagliflozin), depleting neutrophils or Kupffer cells, or inhibiting S100A8/A9 binding to RAGE (using paquinimod), all reduced diabetes-induced thrombocytosis. Inhibiting S100A8/A9 also decreased atherogenesis in diabetic mice. Finally, we found that patients with type 2 diabetes have reticulated thrombocytosis that correlates with glycated hemoglobin as well as increased plasma S100A8/A9 levels. These studies provide insights into the mechanisms that regulate platelet production and may aid in the development of strategies to improve on current antiplatelet therapies and to reduce cardiovascular disease risk in diabetes.
Can dried blood spots be used for diagnosis of chronic hepatitis C virus infection, even if they are stored under non-ideal conditions?
Authors: M. Van Tilborg, G. Heymann, V. Cherepanov, A. Aquino, T. Mazzulli, M. Kowgier, H.L. Janssen, G. Cloherty, M. Biondi, J. Feld
Journal: Journal of Hepatology (2017)
Validation of the Baveno VI criteria for the screening of gastroesophageal varices in our hospital
Authors: G.M. Arriero, M.J. Palacios, N.R.R. Campos, L.M. Ron, D.V. Vidal, L.V. Ayala, B.Á. Cuenllas, P.L. Torres, F.J. Plaza
Journal: Journal of Hepatology (2017)
Passive enhanced safety surveillance for Vaxigrip and Intanza 15 µg in the United Kingdom and Finland during the northern hemisphere influenza season 2015/16
Authors: Hélène Bricout, Anne Laure Chabanon, Audrey Souverain, Christine Sadorge, Timo Vesikari, Timothy David Caroe
Journal: Eurosurveillance (2017)

Enhanced safety surveillance (ESS) was conducted in the United Kingdom and Finland for Vaxigrip and Intanza 15 µg to comply with the European Medicines Agency interim guidance aimed to detect any potential increase in reactogenicity in near real time following the annual update of the influenza vaccine strain composition. This pilot passive ESS was established to strengthen safety monitoring by facilitating spontaneous vaccinee reports and estimating near real-time vaccinee exposure. The primary objective was to estimate the reporting rates of suspected adverse reactions (ARs) occurring within 7 days post vaccination during the northern hemisphere 2015/16 influenza season. Among the Vaxigrip vaccinees (n = 1,012), 32 (3.2%) reported a total of 122 suspected ARs, including 110 suspected ARs that occurred within 7 days post vaccination. Among the Intanza 15 µg vaccinees (n = 1,017), 31 (3.0%) reported a total of 114 suspected ARs, including 99 that occurred within 7 days post-vaccination. These results were consistent with the known safety profile of the two vaccines and did not show any change in reactogenicity or safety concerns. This passive ESS showed improved data reporting and demonstrated its suitability to health authorities’ requirements; further fine tuning of the methodology is under discussion between all stakeholders.
Natural Variation in the Distribution and Abundance of Transposable Elements Across the Caenorhabditis elegans Species
Authors: K.M. Laricchia, S. Zdraljevic, D.E. Cook, E.C. Andersen
Journal: Molecular Biology and Evolution (2017)

Transposons are mobile DNA elements that generate both adaptive and deleterious phenotypic variation thereby driving genome evolution. For these reasons, genomes have mechanisms to regulate transposable element (TE) activity. Approximately 12-16% of the Caenorhabditis elegans genome is composed of TEs, of which the majority are likely inactive. However, most studies of TE activity have been conducted in the laboratory strain N2, which limits our knowledge of the effects of these mobile elements across natural populations. We analyzed the distribution and abundance of TEs in 208 wild C. elegans strains to better understand how transposons contribute to variation in natural populations. We identified 3,397 TEs as compared with the reference strain, of which 2,771 are novel insertions and 241 are TEs that have been excised in at least one wild strain. Likely because of their hypothesized deleterious effects, we find that TEs are found at low allele frequencies throughout the population, and we predict functional effects of TE insertions. The abundances of TEs reflect their activities, and these data allowed us to perform both genome-wide association mappings and rare variant correlations to reveal several candidate genes that impact TE regulation, including small regulatory piwi-interacting RNAs and chromatin factors. Because TE variation in natural populations could underlie phenotypic variation for organismal and behavioral traits, the transposons that we identified and their regulatory mechanisms can be used in future studies to explore the genomics of complex traits and evolutionary changes.
RIPK1 suppresses a TRAF2-dependent pathway to liver cancer
Authors: A.T. Schneider, J. Gautheron, M. Feoktistova, C. Roderburg, S.H. Loosen, P. Schemmer, M.W. Büchler, U.P. Neumann, F. Tacke, C. Trautwein, T. Longerich, M. Vucur, T. Luedde
Journal: Journal of Hepatology (2017)
BMS-986036 (pegylated FGF21) in patients with non-alcoholic steatohepatitis: a phase 2 study
Authors: A. Sanyal, E.D. Charles, B. Neuschwander-Tetri, R. Loomba, S. Harrison, M. Abdelmalek, E. Lawitz, D. Halegoua-DeMarzio, Y. Dong, S. Noviello, S. Krishnamoorthy, Y. Luo, R. Christian
Journal: Journal of Hepatology (2017)
Molecular characterization of the immune class of hepatocellular carcinoma
Authors: I. Martinez-Quętglas, D. Sia, Y. Jiao, O. Kuchuck, C.V. Martin, M.C. De Moura, J. Putra, G. Camprecios, S. Thung, V. Mazzaferro, M. Esteller, A. Villanueva, J.M. Llovet
Journal: Journal of Hepatology (2017)