tbuckley/cabot-search huggingface dataset:
Clinical Pharmacopsychology: Conceptual Foundations and Emerging Tasks
Authors: Giovanni A. Fava, Elena Tomba, Per Bech
Journal: Psychotherapy and Psychosomatics (2017)

The aim of this critical review was to outline emerging trends and perspectives of clinical pharmacopsychology, an area of clinical psychology that is concerned with the psychological effects of medications. The historical development of clinical pharmacopsychology is outlined, with discussion of its most representative expressions and reference to current challenges of clinical research, with particular reference to clinimetrics. The domains of clinical pharmacopsychology encompass the clinical benefits of psychotropic drugs, the characteristics that predict responsiveness to treatment, the vulnerabilities induced by treatment (side effects, behavioral toxicity, iatrogenic comorbidity), and the interactions between drug treatment and psychological variables. Its aim is to provide a comprehensive assessment of the clinical important changes that are concerned with (a) wanted and expected treatment effects, (b) treatment-induced unwanted side effects, and (c) the patient's own personal experience of a change in terms of well-being and/or quality of life. Clinical pharmacopsychology offers a unifying framework for the understanding of clinical phenomena in medical and psychiatric settings. Research in this area deserves high priority.
Noninvasive serum biomarkers reflect the effect of Aramchol on mice fibrotic livers
Authors: M. Iruarrizaga-Lejarreta, L. delaCruz-Villar, M. Varela-Rey, R. Mayo, I. Martínez-Arranz, D. Fernández-Ramos, L. Hayardeny, C. Alonso, J. Anguita, M.L. Martínez-Chantar, J.M. Mato
Journal: Journal of Hepatology (2017)
Timing of Elective Repeat Cesarean Delivery at Term and Neonatal Outcomes
Authors: Alan T.N. Tita, Mark B. Landon, Catherine Y. Spong, Yinglei Lai, Kenneth J. Leveno, Michael W. Varner, Atef H. Moawad, Steve N. Caritis, Paul J. Meis, Ronald J. Wapner, Yoram Sorokin, Menachem Miodovnik, Marshall Carpenter, Alan M. Peaceman, Mary J. O'Sullivan, Baha M. Sibai, Oded Langer, John M. Thorp, Susan M. Ramin, Brian M. Mercer
Journal: New England Journal of Medicine (2009)

Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes.
Diabetes predisposes patients to atrial fibrillation after robotic-assisted video-thoracoscopic pulmonary lobectomy
Authors: S. Reynolds, J. Glover, M. Echavarria, E. Ng, F. Velez-Cubian, C. Moodie, J. Garrett, J. Fontaine, E. Toloza
Journal: Annals of Oncology (2017)
Safety and efficacy of Ombitasvir, Paritaprevir/Ritonavir and Dasabuvir with or without ribavirin in chronic hepatitis C patients receiving opioid substitution therapy: a pooled analysis across 12 clinical trials
Authors: J. Grebley, M. Puoti, H. Wedemeyer, C. Cooper, M.S. Sulkowski, G. Foster, T. Berg, E. Villa, F. Rodriguez-Perez, D.L. Wyles, N.N. Alami, Z. Zhang, E. Dumas, G.J. Dore
Journal: Journal of Hepatology (2017)
Combination of Ublituximab, TGR-1202, and Bendamustine Demonstrates Significant Activity in Patients with Advanced DLBCL and Follicular Lymphoma
Authors: Matthew Lunning, Philip J Bierman, R. Gregory Bociek, Marshall T. Schreeder, Susan Blumel, Kathy Cutter, Emily K. Pauli, Peter Sportelli, Hari P. Miskin, Michael S. Weiss, Julie M Vose
Journal: Blood (2016)
The gut microbiome of lean patients with non-alcoholic steatohepatitis: comparison with overweight/obese counterparts and healthy subjects, correlation with dietary intake and liver histology
Authors: S.M. Duarte, J.T. Stefano, L. Miele, F.R. Ponziani, M. Souza, L. Rodrigues, F.G. Costa, K. Toda, D.F. Mazo, E.C. Sabino, F.J. Carrilho, A. Gasbarrini, C.P. Oliveira
Journal: Journal of Hepatology (2017)
Referral pathways for patients with non-alcoholic fatty liver disease based on non-invasive fibrosis tests: diagnostic accuracy and cost analysis of a two-tier approach
Authors: A. Majumdar, C. Crossan, D. Thorburn, A. Srivastava, W. Rosenberg, M. Pinzani, L. Longworth, E.A. Tsochatzis
Journal: Journal of Hepatology (2017)
Interleukin-33/interleukin-33r signaling promotes liver inflammation and fibrogenesis in obesogenic model of nonalcoholic steatohepatitis in mice
Authors: N. Jovicic, I. Jeftic, M.M. Kovacevic, I. Tanaskovic, N. Arsenijevic, M.L. Lukic, N. Pejnovic
Journal: Journal of Hepatology (2017)
HIV/HCV-coinfected cirrhotic patients are no longer at higher risk of hepatocellular carcinoma or end-stage liver disease as compared to HCV-monoinfected patients (ANRS CO12 CirVir and ANRS CO13 HEPAVIH cohorts)
Authors: D. Salmon, P. Nahon, R. Layese, V. Bourcier, E. Audureau, C. Gilbert, L. Esterle, F. Dabis, L. Wittkop, F. Roudot-Thoraval
Journal: Journal of Hepatology (2017)
Re: Pascal Rischmann, Albert Gelet, Benjamin Riche, et al. Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate cancer: A Prospective Multicentric Hemiablation Study of 111 Patients. Eur Urol 2017;71:267–73
Authors: Lampros Mitrakas
Journal: European Urology (2017)
Serial combination of noninvasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with nonalcoholic fatty liver disease
Authors: S. Petta, V.W. Wong, C. Cammà, J.-B. Hiriart, G.L. Wong, J. Vergniol, A.W. Chan, V. Di Marco, W. Merrouche, H.L. Chan, F. Marra, B. Le-Bail, U. Arena, A. Craxì, V. de Ledinghen
Journal: Journal of Hepatology (2017)
Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase mutations
Authors: Chad A. Newton, Kiran Batra, Jose Torrealba, Keith Meyer, Ganesh Raghu, Christine Kim Garcia
Journal: European Respiratory Journal (2017)

We thank H. Nunes and colleagues for their interest in our study of patients with telomere-related gene mutations associated with pleuroparenchymal fibroelastosis (PPFE) [1]. Their cohort of five patients with PPFE and rare variants in telomerase reverse transcriptase ( TERT ) is similar to ours with regard to its female predominance. Here we provide additional details of our eight cases to point out additional similarities and differences between these two cohorts (table 1). A diagnosis of PPFE is linked to pathogenic variants in three different telomere-related genes <http://ow.ly/eGOq30aPkgx>
Generation and Signaling Function of CD19 Chimeric Antigen Receptor Modified CD8+ T Cells Derived From Virus-Specific Central Memory Cells for Adoptive Therapy After Allogeneic Hematopoietic Stem Cell Transplant
Authors: Seitaro Terakura, Tori N. Yamamoto, Rebecca A. Gardner, Cameron J. Turtle, Michael C. Jensen, Stanley R. Riddell
Journal: Blood (2011)
Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer
Authors: Fei Ma, Qiao Li, Shanshan Chen, Wenjie Zhu, Ying Fan, Jiayu Wang, Yang Luo, Puyuan Xing, Bo Lan, Meiying Li, Zongbi Yi, Ruigang Cai, Peng Yuan, Pin Zhang, Qing Li, Binghe Xu
Journal: Journal of Clinical Oncology (2017)

Purpose This phase I study assessed the safety, tolerability, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Patients and Methods Pyrotinib was administered continuously, orally, once per day to patients who did not have prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was 80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood samples were collected on day 1 and day 28. Next-generation sequencing was performed on circulating tumor DNA and genomic DNA from tumor samples. Results Thirty-eight patients were enrolled. The dose-limiting toxicity was grade 3 diarrhea, which occurred in two patients administered 480 mg of pyrotinib; thus, the maximum tolerated dose was 400 mg. Common pyrotinib-related adverse events included diarrhea (44.7% [17 of 38]), nausea (13.2% [five of 38]), oral ulceration (13.2% [five of 38]), asthenia (10.5% [four of 38]), and leukopenia (10.5% [four of 38]). The only grade 3 adverse event was diarrhea. Pharmacokinetic analyses indicated that pyrotinib exposure was dose dependent. The overall response rate was 50.0% (18 of 36), and the clinical benefit rate (complete response + partial response + stable disease ≥ 24 weeks) was 61.1% (22 of 36). The median progression-free survival was 35.4 weeks (95% CI, 23.3 to 40.0 weeks). The overall response rate was 83.3% (10 of 12) in trastuzumab-naive patients and 33.3% (eight of 24) in trastuzumab-pretreated patients. Preliminary results suggest that PIK3CA and TP53 mutations in circulating tumor DNA ( P = .013) rather than in archival tumor tissues ( P = .474) may predict the efficacy of pyrotinib. Conclusion Continuous once-per-day pyrotinib was well tolerated and demonstrated promising antitumor activity in HER2-positive patients with metastatic breast cancer. The maximum tolerated dose was established as 400 mg. Diarrhea was the dose-limiting toxicity. The promising antitumor activity and acceptable tolerability of pyrotinib warrant its further evaluation in a phase II study.
Radioembolization for the treatment of hepatocellular carcinoma
Authors: Hyo-Cheol Kim
Journal: Clinical and Molecular Hepatology (2017)

Transarterial radioembolization (TARE) with yttrium 90 (90Y), an intra-arterial procedure performed by interventional radiologists, has begun being utilized in managing hepatocellular carcinoma (HCC) in Korea. There are two available TARE products: glass and resin microspheres with different physical characteristics. All patients undergoing TARE must be assessed with clinical examination and laboratory tests as well as a thorough angiographic evaluation. TARE is safe and effective in the treatment of unresectable HCC, as it has longer time-to-progression, greater ability to downsize tumors for liver transplantation, less post-embolization syndrome, and shorter hospitalization compared with chemoembolization. TARE can also serve as an alternative to ablation, surgical resection, portal vein embolization, and sorafenib. The utility of TARE continues to expand with new insights in interventional oncology. Keywords: Hepatocellular carcinoma; Radioembolization; Transarterial radioembolization (TARE); Yttrium-90 (90Y)
Abstract IA09: Translational control of the tumor microenvironment
Authors: Nathaniel Robichaud, Qianyu Guo, Sonia del Rincon, Wilson H. Miller, Peter Siegel, Brian Hsu, Nahum Sonenberg
Journal: Cancer Research (2017)

Abstract Translational control has emerged as a critical determinant in tumorigenesis. The mRNA cap-binding protein eIF4E is an oncoprotein that plays an important role in cancer initiation and progression. We recently demonstrated that eIF4E phosphorylation on serine 209 by the Map Kinase Integrating Kinases (MNK1/2) promotes epithelial to mesenchymal transition, invasion and metastasis. We recently discovered a critical importance of eIF4E phosphorylation in the tumor microenvironment (TME) for the metastatic process. To investigate the role of eIF4E phosphorylation in the TME, we utilized a syngeneic model in which a murine mammary tumor cell line (66cl4) was orthotopically injected into mice bearing the non-phosphorylatable eIF4E ^S209A mutation and their WT counterparts. Tumor growth was monitored by caliper measurements, and tissues were collected for histological assessment and immunohistochemistry. The onset of tumor formation was significantly delayed in eIF4E ^S209A mice. However, established tumors showed no differences in growth, proliferation, apoptosis, vascularization or immune infiltration. Strikingly, eIF4E ^S209A mice were nearly completely resistant to the formation of lung metastases from primary mammary tumors. Metastatic potential in this model was correlated with neutrophil accumulation in the spleen, blood and lungs of WT mice, which was significantly reduced in eIF4E ^S209A mice. Furthermore, treatment of tumor-bearing WT mice with an inhibitor of MNK1/2 significantly reduced lung metastasis without affecting primary tumor growth. Considering that eIF4E phosphorylation in both the TME and cancer cells promotes metastasis, our findings support the development of MNK inhibitors for metastasis prevention. Citation Format: Nathaniel Robichaud, Qianyu Guo, Sonia del Rincon, Wilson H. Miller, Peter Siegel, Brian Hsu, Nahum Sonenberg. Translational control of the tumor microenvironment. [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 IA09.
Guanylyl cyclase C (GCC) expression in lymph nodes (LNs) as a determinant of recurrence in stage II colon cancer (CC) patients (pts).
Authors: Daniel J. Sargent, Qian Shi, Sharlene Gill, Christophe Louvet, Richard Bernard Everson, Udo Kellner, Thomas E. Clancy, J. Marc Pipas, Murray B. Resnick, Michael O. Meyers, David Huntsman, Pierre Validire, Umar Farooq, Emily S Pavey, Jean-Francois Haince, Guillaume Beaudry, Yves Fradet
Journal: Journal of Clinical Oncology (2013)

3639 Background: The first phase of the multi-center prospectively specified retrospective study Validating Indicators To Associate Recurrence (VITAR), assessing the relationship between GCC gene expression in formalin fixed (FFPE) LNs and time to recurrence (TTR) in stage II CC pts not treated with adjuvant chemotherapy (Sargent, Annals Surg Onc 2011), showed promising initial results. Here we report a validation set of 463 new stage II CC pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs from untreated T3N0 CC pts diagnosed from 1999-2008 with at least 12 LNs examined , blinded to clinical outcomes. Patients were classified by GCC LN ratio (LNR) (high risk: LNR &gt; 0.1; low risk: LNR ≤ 0.1), with LNR defined as ratio of GCC positive to GCC informative LNs. Cox regression models tested the relationship between GCC and the primary endpoint of TTR, adjusted for age, tumor grade, number of LN examined pathologically, and lymphovascular invasion. Mismatch repair (MMR) status was also assessed. All primary analyses and cut-points were pre-specified. Results: 46pts (10%) recurred (rec), median follow-up was 65 months, median LNs examined was 20, and 42% (195/463) were classified high risk. Overall, TTR was not significantly associated with binary GCC LNR risk class (HR=1.47, p=.208) or DFS (HR= 1.39, p=.097). One site’s (n=97) tissue grossing method precluded appropriate LN assessment with existing GCC qualification methods. Excluding this site resulted in a TTR HR=1.91, p=0.051 (multivariate). In a post-hocanalysis excluding this site and using a 3-level GCC risk group of high (LNR &gt; 0.20), intermediate (0.10 &lt; LNR &lt; 0.20) and low (LNR &lt; 0.10), high risk group pts had a 5-yr rec risk of 22% versus 8% in low risk (HR 2.72, p=0.006). MMR status was not significantly associated with TTR (multivariate p=0.30). Conclusions: GCC status is a promising prognostic factor in appropriately staged stage II CC pts not treated with adjuvant therapy independent of traditional histopathology risk factors, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique. Outcome associations were strengthened when considering a 3-level GCC categorization.
Integrative whole-genome copy number analysis and mutation profiling of FFPE brain tumor specimens and potential in designing multi-arm clinical trials.
Authors: Shakti Ramkissoon, Wenya L. Bi, Sam Haidar, Jane B. Cryan, David A. Reardon, Eudocia Quant Lee, Mikael L. Rinne, Andrew David Norden, Lakshmi Nayak, Andrea Lyn Russo, Nils D. Arvold, Sandro Santagata, Ian F. Dunn, Rebecca D. Folkerth, Neal Ian Lindeman, Rameen Beroukhim, Azra Ligon, Patrick Y. Wen, Brian Michael Alexander, Keith L. Ligon
Journal: Journal of Clinical Oncology (2014)

11098 Background: Multi-dimensional cancer genotyping has the potential to advance clinical diagnostics and improve results of clinical trials by identifying targetable genomic aberrations for glioblastoma (GBM). However, prospective use of formalin-fixed paraffin-embedded (FFPE) clinical samples for multiplex copy number and somatic mutation genotyping in clinical trials is not yet routinely performed. We evaluated feasibility and implemented a combined copy number and clinical research mutation-testing program (PROFILE) in a CLIA-certified laboratory. Methods: We collected molecular profiling results from clinical and clinical research testing on 250 GBM patients from the Brigham and Women’s Hospital Center for Advanced Molecular Diagnostics. These data included array comparative genomic hybridization (OncoCopy, n=250), mass spectrometry-based mutation genotyping (OncoMap, n=86), and targeted cancer exome sequencing of 275 known cancer genes (OncoPanel, n=98). Results: We successfully reported OncoCopy profiles for 42 relevant loci in 97% of samples and demonstrated that analysis of 250 GBMs reliably detected amplifications or structural variations in common drug targets for clinical trials (EGFR, EGFRvIII, MET, MDM2, MDM4, PDGFRA, CDK4, and CDK6) at expected frequencies. OncoMap results for 86 GBMs revealed recurrent mutations in IDH1, BRAF, PIK3CA, and PIK3R1 while less frequent mutations were detected in tumor suppressor genes TP53, PTEN and RB1. OncoPanel results were reported on >90% of patients and comprehensively detected known mutations of diagnostic, prognostic and therapeutic relevance (e.g. IDH1 p.R132H, BRAF p.V600E). Tumor suppressor gene mutations and variants were robustly detected allowing for integrative OncoCopy and OncoPanel reporting in 65% of cases. Conclusions: These complementary clinical assays allowed efficient and reliable identification of diagnostic aberrations that serve as clinically actionable drug targets, which could be incorporated into genomically stratified multi-arm clinical trial design for GBM.
Expression of the bile acid receptor TGR5 in livers of PSC patients and Mdr2 -/- (Abcb4 -/- ) mice
Authors: M. Reich, L. Spomer, J. Hoehne, J.E. Hov, T.H. Karlsen, D. Nierhoff, D. Häussinger, V. Keitel
Journal: Journal of Hepatology (2017)
Abstract B42: Combination of liquid chromatography-surface enhanced Raman spectroscopy and liquid chromatography-mass spectrometry to identify SUMOylated proteins due to nutrient restriction in colorectal cancer
Authors: Monica M. Schroll, Zachary D. Schultz, Amanda B. Hummon
Journal: Cancer Research (2017)

Abstract Nutrient restriction, also known as caloric restriction, has been extensively examined for its positive impact on lifespan, immune system boost, and aging. Nutrient restriction, defined as providing essential nutrients but restricting total caloric intake, has shown to decrease disease rate in humans. In addition, nutrient restriction is implicated in decreasing cancer initiation and progression. We have previously established three dimensional cell culture models, known as spheroids, in the HCT 116 colorectal cancer cell line as a high throughput model for studying the proteomic changes associated with nutrient restriction. We found that SUMOylated proteins are up regulated in colorectal cancer 3D cell cultures when subjected to metabolic stress. The attachment of the SUMO protein leads to changes in subcellular location, DNA repair, transcriptional regulation, and mitosis. We will explore SUMOylated in response to nutrient restriction via a novel technique to detect biomolecules using LC-SERS. This method allows the can detection of chemical differences associated with biomolecule structure. We first will enhance this system to detect and quantify metabolites in a more complex matrix, such as a cell lysate. Once the methodology has been optimized we use LC-SERS to identify and quantitate SUMOylated proteins in response to NR. When compared to available MS methods to identified SUMOylated proteins, we hypothesize our novel LC-SERS methodology will be able to surpass the limitations found with MS methods. Nutrient restriction has overwhelming effects on cancer and this study will provides further evidence that SUMOlyation, in response to metabolic stress, has a role in cancer progression. Citation Format: Monica M. Schroll, Zachary D. Schultz, Amanda B. Hummon. Combination of liquid chromatography-surface enhanced Raman spectroscopy and liquid chromatography-mass spectrometry to identify SUMOylated proteins due to nutrient restriction in colorectal cancer. [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 B42.
Do rapid diagnostic tests improve overall quality of care?
Authors: Emily W Johansson, Helena Hildenwall, Humphreys Nsona, Valentina Buj de Lauwerier, Stefan Swartling Peterson
Journal: BMJ (2017)

Hopkins and colleagues show that implementation of rapid diagnostic tests, although reducing overuse of malaria drugs, might increase unwarranted prescription of antibiotics.1 The paper focuses heavily on treatment outcomes, but quality of care is more important. Do rapid diagnostic tests improve overall quality of care, which could lead to more rational prescribing of antimicrobials?

Our recent analysis, based on a …
The cytotoxic prodrug, AQ4N, demonstrates tumor targeting and accumulation resulting in anti-tumor activity in the BxPC3 pancreatic xenograft model
Authors: Susan E. Alters, Alvin Wong, Alshad S. Lalani, W. D. Henner
Journal: Cancer Research (2006)

3827  Introduction: AQ4N (banoxantrone; 1,4 bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione bis N-oxide) is a targeted cytotoxic prodrug that is bioreduced to AQ4, a highly potent DNA topoisomerase II inhibitor cytotoxic to proliferating cells. The anti-tumor activity, targeting and accumulation of AQ4N was investigated in a pancreatic xenograft model, BxPC3. Experimental Methods: The in vitro activity of AQ4 and AQ4N on BxPC3 cells was determined by MTT assay following a 24 hour incubation with drug. The anti-tumor efficacy of AQ4N was determined in subcutaneous (SC) and orthotopic (OT) models of human BxPC3 tumor implants in nude mice. For the SC model, BxPC3 tumor fragments were implanted and tumors allowed to grow to ∼100 mm3 prior to treatment; response was evaluated as tumor growth inhibition. For the OT model, BxPC3 tumor cells were injected into the pancreas parenchyma, AQ4N treatment was initiated on day 14 post-graft and prolongation of survival was evaluated by Kaplan-Meier analysis. Levels of AQ4N and AQ4 were measured in BxPC3 tumor and mouse plasma and tissue at various time points following a single intravenous dose of 20 mg/kg AQ4N using an HPLC/MS-MS method. Results: The cytotoxic activity of AQ4N, its bioreduced metabolite, AQ4, and the anti-neoplastic agent, gemcitabine were screened against the BxPC3 tumor line in vitro. While AQ4N was inactive, AQ4 demonstrated potent cytotoxic activity with an IC50 of 1.6μM; gemcitabine demonstrated an IC50 of 0.06μM. In the SC BxPC3 pancreatic carcinoma model AQ4N provided significant tumor growth inhibition (58%) compared to the vehicle treated negative control group (p
Baseline characteristics of participants in pl-208: A multi-center trial of the prolung test™ (Transthoracic Bioconductance Measurement) as an adjunct to CT chest scans for the risk stratification of patients with pulmonary lesions suspicious for lung cancer
Authors: R.C. Yung, D. Ost, M. Simoff, C. Reddy, A. Goyal, I. Barjakarevic, M. Garff, K. Larson, J. O'Driscoll, S. Makani
Journal: Annals of Oncology (2017)