tbuckley/cabot-search huggingface dataset:
Medicine and books: Rationing: Talk and Action in Health Care
Authors: Stephen Leeder
Journal: BMJ (1998)

Ed Bill New 

BMJ Publishing Group, £24.95, pp 261 

ISBN 0 7279 1180 5 

The Rationing Agenda Group was formed in 1995 to promote a serious debate about rationing in the NHS. Rationing: Talk and Action in Health Care chronicles the work of the Rationing Agenda Group—its setting of agendas, early consultation with health service managers, and inquiry into public understanding of rationing (virtually nil). Is it possible to define a package of core services that the NHS should provide? Should we be aiming to “maximise the health of the whole community” or the health of a few who are ill? How legitimate is it to ration according to age? Should rationing be determined centrally or peripherally in the healthcare system? Should it be explicit? Should the public be involved in rationing, and if so how? Exploration in the form of reports of these debates occupies six chapters—the talk, as implied by the title of the book. 

Then follow six instructive case studies—the action—relating the experience with rationing in New Zealand and Sweden; the possible use of citizen juries in setting priorities; the Asbury draft policy on ethical uses of resources; the experience of a purchaser in coping with demands for interferon; and an example from Adelaide, Australia, where the painful realities of restricting drugs within public hospitals is considered. 

The pervasive theme of this splendid collection of debates and reflections is that rationing is far more widespread than we would at first think. It is often implicit, and hence out of sight, but nevertheless there. Its inevitability is an important quality to be recognised if we are to live with it in some degree of comfort. 

A second theme is that good people worry about rationing; this may not make them comfortable, but it is worry with vicarious benefit. The book perhaps best illustrates this in the case study of a draft policy on the ethical allocation of resources. The policy makes explicit the values and intentions held by doctors in a fundholding general practice (Asbury) and describes how the doctors apply these values in managing their patients. This fine professional document also engages patients in the discussion in a way that theoretical debates never do. It exemplifies that at the core of “ration” is the root “ratio” or reason. Here, doctors explain how they will cope with the dual demands on them—of doing their best for individual patients and managing an overall budget that is insufficient for the best care of every person—and then consider a range of practical possibilities to show how decisions would be made when rationing was necessary. This is talk and action in fine combination.
The dexamethasone suppression test in depressed outpatients and normal control subjects
Authors: E D Peselow, N Goldring, R R Fieve, R Wright
Journal: American Journal of Psychiatry (1983)

In contrast to a recently published report by Amsterdam and associates, the authors noted a higher frequency of abnormal dexamethasone suppression test results in 88 outpatients with primary depression (particularly the endogenous subtype) than in 49 normal controls.
Unrelated Cord Blood Transplanation for Malignant Lymphoma: A Retrospective Study from the Japan Cord Blood Bank Network (JCBNW).
Authors: Morihito Takita, Koichiro Yuji, Takuhiro Yamaguchi, Tomoko Matsumura, Masahiro Kami, Hisashi Sakamaki, Yasushi Kouzai, Masaya Okada, Yuko Osugi, Ryuji Kobayashi, Masami Inoue, Satoshi Takahashi, Makoto Murata, Shunro Kai, Koji Kato, Tokiko Nagamura, Shuichi Taniguchi, Shunichi Kato
Journal: Blood (2007)
Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity
Authors: Stefano Di Biase, Changhan Lee, Sebastian Brandhorst, Brianna Manes, Roberta Buono, Chia-Wei Cheng, Mafalda Cacciottolo, Alejandro Martin-Montalvo, Rafael de Cabo, Min Wei, Todd E. Morgan, Valter D. Longo
Journal: Cancer Cell (2016)
Immune checkpoint blockade as a potential therapeutic target: surveying CNS malignancies
Authors: Sarah T. Garber, Yuuri Hashimoto, Shiao-Pei Weathers, Joanne Xiu, Zoran Gatalica, Roel G. W. Verhaak, Shouhao Zhou, Gregory N. Fuller, Mustafa Khasraw, John de Groot, Sandeep K. Reddy, David Spetzler, Amy B. Heimberger
Journal: Neuro-Oncology (2016)

Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. Patients with CNS malignancies were profiled by Caris Life Sciences from 2009 to 2016. Immunohistochemistry findings for PD-1 on tumor-infiltrating lymphocytes (TIL) and PD-L1 on tumor cells were available for 347 cases. Next-generation sequencing, pyrosequencing, immunohistochemistry, fragment analysis, and fluorescence in situ hybridization were used to determine isocitrate dehydrogenase 1 (IDH1), phosphatase and tensin homolog (PTEN), and tumor protein 53 mutational status, O6-DNA methylguanine-methyltransferase promoter methylation (MGMT-Me) status, PTEN expression, plus epidermal growth factor receptor variant III and 1p/19q codeletion status. PD-1+ TIL expression and grade IV gliomas were significantly positively correlated (odds ratio [OR]: 6.363; 95% CI: 1.263, 96.236)—especially in gliosarcomas compared with glioblastoma multiforme (P = .014). PD-L1 expression was significantly correlated with tumor grade with all PD-L1+ cases (n = 21) being associated with grade IV gliomas. PD-1+ TIL expression and PD-L1 expression were significantly correlated (OR: 5.209; 95% CI: 1.555, 20.144). Mutations of PTEN, tumor protein 53, BRAF, IDH1, and epidermal growth factor receptor or MGMT-Me did not associate with increased intratumoral expression of either PD-1+ TIL or PD-L1 in glioblastoma multiforme even before false discovery rate correction for multiple comparison. Targeting immune checkpoints in combination with other therapeutics based on positive biomarker selection will require screening of large patient cohorts.
Studies on the Mechanism of Action of Chemotherapeutic Agents in Cancer. IV. Relationship of Guanine and Guanylic Acid to the Action of Guanazolo on Lymphoid Tumors in Mice and Rats&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: Abraham Goldin, Ph. D., Ezra M. Greenspan, M. D., Emanuel B. Schoenbach, M. D.
Journal: JNCI Journal of the National Cancer Institute (1950)

Studies on the Mechanism of Action of Chemotherapeutic Agents in Cancer. IV. Relationship of Guanine and Guanylic Acid to the Action of Guanazolo on Lymphoid Tumors in Mice and Rats Get access Abraham Goldin, Ph. D., Abraham Goldin, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ezra M. Greenspan, M. D., Ezra M. Greenspan, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Emanuel B. Schoenbach, M. D. Emanuel B. Schoenbach, M. D. Clinical Research Unit of the National Cancer Institute, U. S. Public Health Service, U. S. Marine Hospital, and the Department of Preventive Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 11, Issue 2, October 1950, Pages 319–338, https://doi.org/10.1093/jnci/11.2.319 Published: 01 October 1950 Article history Received: 09 July 1950 Published: 01 October 1950
ATPS-72A NOVEL CXCR4 ANTAGONIST COMBINES SYNERGISTICALLY WITH BEVACIZUMAB AND SUNITINIB TO INHIBIT PROGRESSION OF GLIOBLASTOMA
Authors: Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Ana Jitariuc, Simona Delle Monache, Adriano Angelucci, Peter Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
Journal: Neuro-Oncology (2015)

BACKGROUND: SDF1 and its receptor CXCR4 are strongly implicated in the maintenance of the highly aggressive cancer Glioblastoma multiforme (GBM). SDF1 and CXCR4 are also involved in the recruitment of vasculogenic precursors from the bone marrow, so we hypothesized that combining the anti-vasculogenic activity of CXCR4 inhibition with anti-angiogenic therapy would have profound anti-tumor activity. CXCR4 inhibition was achieved through the use of Compound B, a high affinity (Ki <10nM), highly selective, small molecule, brain penetrant CXCR4 antagonist which inhibits xenograft progression in nude mice after irradiation and/or temozolomide. METHODS: The expression of CXCR4 and release of CXCL12 in three human glioma cell lines (U87, U251 and T98G) was measured in vitro. Xenograft tumours (s.c.) were induced using 2 x106 cells in groups of 8 SCID mice, and after the tumours had grown to 100mm3 the mice were randomized to receive vehicle, bevacizumab (4 mg/kg iv every 4 days), sunitinib (40mg/kg po qd) or Compound B (50mg/kg po qd), bevacizumab plus Compound B or sunitinib plus Compound B. The same dosing schedules (but without sunitinib) were used in intracranial experiments using tumours induced by 105 luciferase labelled U87 cells. Time to progression (doubling of tumour size) was assessed. RESULTS: The GBM cell lines expressed CXCR4 and released CXCL12 in vitro. In vivo Compound B inhibited the progression of U87, U251 and T98G xenografts (s.c.), to approximately the same extent as bevacizumab and sunitinib, while the combination of Compound B with either anti-angiogenic agent showed a synergistic inhibition of tumour progression (p < 0.0001 with all three cell lines). Subsequently the effect of the combination of Compound B with bevacizumab on U87 intracranial tumours was investigated. CONCLUSION: Compound B may be used in combination with anti-angiogenic treatments to inhibit the progression of GBM.
The NATCH trial: Observations on the neoadjuvant arm
Authors: E. Felip, R. Rosell, B. Massuti, G. Alonso, J. L. González-Larriba, C. Camps, D. Isla, C. Mas, J. J. Sanchez, J. A. Maestre
Journal: Journal of Clinical Oncology (2007)

7578 Background: In early-stage NSCLC the neoadjuvant approach is a promising option since relatively low compliance rate with adjuvant therapy and incomplete recovery after surgery are commonly reported. The NATCH trial was therefore designed to address whether neoadjuvant or adjuvant paclitaxel (P)/carboplatin (C) improves disease-free survival compared to surgery alone in early-stage NSCLC. Patients randomized to the neoadjuvant arm have now undergone analyses of toxicity, radiographic response, resectability and surgical mortality. Methods: Consenting patients with clinical stage I (&gt;2 cm), II, T3N1 NSCLC are randomized to surgery alone or 3 cycles of neoadjuvant PC (P: 200 mg/m 2 / C:AUC=6 on day 1 every 3wk), or surgery followed by 3 cycles of adjuvant PC at the same schedule. Planned sample size of this prospective, randomized trial is 628 patients. Results: Since 2000, 616 patients have been accrued, 200 in the neoadjuvant arm, 208 in the adjuvant arm, and 208 in the surgery arm. Demographic data is now available for 162 patients in the neoadjuvant arm: 89% male; median age 64 years (range, 37–78); 45% PS 0; 53% squamous cell, 27% adenocarcinoma, 13% large cell; 7% stage IA, 64% IB, 2% IIA, 24% IIB, 2.5% T3N1. Neoadjuvant chemotherapy has been well tolerated with a median number of cycles per patient of 3. No unexpected toxicities have been seen with 12% of patients having grade 3–4 neutropenia and 43% grade 1–2 anemia. Major radiographic response has been observed in 59% of patients and progression during chemotherapy occurred in 6%. No patient characteristics were predictive for clinical response. Resection procedures at thoracotomy: lobectomy or bilobectomy in 70%, pneumonectomy in 26%, and explorative thoracotomy due to unresectable disease in 3% of patients. Post-operative mortality was 4%. Median tumor size was 4.5 cm at baseline CT-scan and 2.5 cm at surgery. At surgery, 9% patients had pathologic complete response, 75% N0–1 disease (with persistent T tumor), and 15% pathologic N2 disease. Conclusion: Neoadjuvant chemotherapy in early NSCLC has proven feasible and safe in this large multicenter sample. Chemotherapy compliance has been high and resectability rates as expected. Our findings are comparable with those of previous studies (BLOT and S9900). Mature survival results of the NATCH trial are expected in 2009. No significant financial relationships to disclose.
Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC).
Authors: Tony Mok, Yi-Long Wu, Patricia A, Watson, Jin Zhang, Reshma A. Rangwala, Gilberto Lopes
Journal: Journal of Clinical Oncology (2015)

TPS8105 Background: Tumors can evade an immune response by co-opting the PD-1 pathway. The anti–PD-1 monoclonal antibody pembrolizumab has demonstrated promising efficacy and acceptable safety across doses and schedules in pts with NSCLC enrolled in the phase 1 KEYNOTE-001 trial, with greater efficacy observed in pts with PD-L1+ tumors. In 45 treatment-naive, PD-L1+ pts (n = 42 evaluable by RECIST v1.1 per central review), pembrolizumab provided a 26% ORR and 64% DCR. All 11 responses were ongoing after a median follow-up of 36 wk. The randomized, open-label phase 3 KEYNOTE-042 trial (ClinicalTrials.gov, NCT02220894) will evaluate the efficacy and safety of pembrolizumab vs platinum doublet chemotherapy as first-line therapy for PD-L1+ advanced NSCLC. Methods: Eligible pts with advanced PD-L1+ NSCLC without EGFR sensitizing mutations or ALK translocation and ≥1 measurable lesion will be randomized 1:1 to pembrolizumab 200 mg every 3 wk or investigator's choice of carboplatin plus paclitaxel or carboplatin plus pemetrexed. Randomization will be stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), region (East Asia vs non-East Asia), and PD-L1 expression (strong vs weak [staining in ≥50% vs 1-49% of tumor cells assessed by immunohistochemistry with the 22C3 antibody]). Pembrolizumab will be continued for 35 cycles or until disease progression, intolerable toxicity, or investigator decision; discontinuation is allowed for pts with complete response. Chemotherapy will be given for a maximum of 6 cycles. Pemetrexed maintenance is optional for pts with nonsquamous NSCLC. In both treatment arms, eligible pts may be treated beyond initial radiographic progression. AEs will be collected during and for 30 d after treatment. Response will be assessed every 9 wk per RECIST 1.1 by central review. Survival follow-up will occur every 2 mo. Primary end point is OS in pts with PD-L1–strongly-positive tumors; secondary end points include PFS in strongly positive pts and PFS and OS in all pts. Enrollment began in Nov 2014 and will continue in 28 countries in Asia, Canada, Europe, and South America until the target of 1240 pts is achieved. Clinical trial information: NCT02220894.
Risk Stratification of DLBCL Patients According to NCCN-IPI in Our Hospital
Authors: Yasuhiro Kazuma, Kazunari Aoki, Yotaro Ochi, Yusuke Koba, Yoshimitsu Shimomura, Yosuke Nagahata, Nobuhiko Yamauchi, Yuichiro Ono, Nobuhiro Hiramoto, Sumie Tabata, Noboru Yonetani, Akiko Matsushita, Hisako Hashimoto, Takayuki Ishikawa
Journal: Blood (2014)
Monitoring of Minimal Residual Disease in NPM1 Mutated Acute Myeloid Leukemia (AML) – a Single Center Experience in 27 Patients.
Authors: Dana Dvorakova, Zdenek Racil, Ivo Palasek, Marketa Protivankova, Ivana Jeziskova, Martina Lengerova, Jiri Mayer
Journal: Blood (2009)
16‐Channel Organic Electrochemical Transistor Array for In Vitro Conduction Mapping of Cardiac Action Potential
Authors: Xi Gu, Chunlei Yao, Ying Liu, I‐Ming Hsing
Journal: Advanced Healthcare Materials (2016)

16-Channel organic electrochemical transistor arrays (OECTs) are developed for mapping the propagation and studying the characteristics of action potentials of primary cardiomyocytes. The physiological activities of a rat cardiomyocyte monolayer during a long-term culturing is revealed by this biocompatible, low-cost, and high transconductance organic electronic device. OECT has great potential to be used in cardiac and neuronal drug screening. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point‐mutant β‐catenin
Authors: Junyan Tao, Emily Xu, Yifei Zhao, Sucha Singh, Xiaolei Li, Gabrielle Couchy, Xin Chen, Jessica Zucman‐Rossi, Maria Chikina, Satdarshan P.S. Monga
Journal: Hepatology (2016)

Hepatocellular cancer (HCC) remains a significant therapeutic challenge due to its poorly understood molecular basis. In the current study, we investigated two independent cohorts of 249 and 194 HCC cases for any combinatorial molecular aberrations. Specifically we assessed for simultaneous HMET expression or hMet activation and catenin β1 gene (CTNNB1) mutations to address any concomitant Met and Wnt signaling. To investigate cooperation in tumorigenesis, we coexpressed hMet and β-catenin point mutants (S33Y or S45Y) in hepatocytes using sleeping beauty transposon/transposase and hydrodynamic tail vein injection and characterized tumors for growth, signaling, gene signatures, and similarity to human HCC. Missense mutations in exon 3 of CTNNB1 were identified in subsets of HCC patients. Irrespective of amino acid affected, all exon 3 mutations induced similar changes in gene expression. Concomitant HMET overexpression or hMet activation and CTNNB1 mutations were evident in 9%-12.5% of HCCs. Coexpression of hMet and mutant-β-catenin led to notable HCC in mice. Tumors showed active Wnt and hMet signaling with evidence of glutamine synthetase and cyclin D1 positivity and mitogen-activated protein kinase/extracellular signal-regulated kinase, AKT/Ras/mammalian target of rapamycin activation. Introduction of dominant-negative T-cell factor 4 prevented tumorigenesis. The gene expression of mouse tumors in hMet-mutant β-catenin showed high correlation, with subsets of human HCC displaying concomitant hMet activation signature and CTNNB1 mutations.We have identified cooperation of hMet and β-catenin activation in a subset of HCC patients and modeled this human disease in mice with a significant transcriptomic intersection; this model will provide novel insight into the biology of this tumor and allow us to evaluate novel therapies as a step toward precision medicine. (Hepatology 2016;64:1587-1605).
Self-Knotting of Feeding Tube
Authors: J. P. Y. Ha, W. T. Siu, C. N. Tang, M. K. Li
Journal: Endoscopy (2001)

Figure 1A patient who underwent a three-stage esophagectomy for carcinoma of the esophagus experienced the complications of left vocal cord palsy and choking on swallowing. A feeding tube (2-mm radioopaque PVC tubing, Portex Limited, England) was inserted via endoscopic guidance for nutrition. Upon removal of the tube, we experienced some resistance and the patient complained of retrosternal discomfort. A chest radiograph demonstrated that the tube had become knotted inside the intrathoracic stomach.
Is Sickle Cell Trait Associated with Incident Cardiovascular Outcomes in African Americans?
Authors: Hyacinth Idu Hyacinth, Cara Carty, Gregory L. Burke, Rakhi P. Naik, Robert J. Adams, Beatrice E. Gee, Will Longstreth, Leonard Egede, Daniel T. Lackland, Charles S. Greenberg, Kelly J. Hunt, Mark M. Kindy, Herman Taylor, JoAnn E. Manson, Mattthew Allison, Wilson G. James, Alexander Reiner
Journal: Blood (2014)
Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults: The cardiovascular health study
Authors: Erika F. Brutsaert, Mary L. Biggs, Joseph A. Delaney, Luc Djoussé, John S. Gottdiener, Joachim H. Ix, Francis Kim, Kenneth J. Mukamal, David S. Siscovick, Russell P. Tracy, Ian H. de Boer, Christopher R. deFilippi, Jorge R. Kizer
Journal: Metabolism (2016)
Abstract 1: Nucleolar Proteins Controlling Cardiac Phenotype in Rat Myocytes and Zebrafish Revealed by Chromatin Proteomics
Authors: Emma Monte, Kevin Mouillesseaux, Haodong Chen, Shuxun Ren, Yibin Wang, Jau-Nian Chen, Thomas M Vondriska, Sarah Franklin
Journal: Circulation Research (2012)

Cardiac hypertrophy is a common precursor to heart failure, during which cardiomyocytes grow to compensate for an increased workload. Hypertrophic cardiomyocytes undergo significant changes in cellular plasticity by adopting the expression profile and some phenotypic aspects of more primitive (embryonic or fetal) cardiac cells. These global changes in gene expression, conserved between humans and animal models of heart failure, must be preceded by structural alterations to the chromatin. Specifically, chromatin regions must be architecturally modified to allow or deny access for transcriptional machinery. However, the proteins responsible for remodeling chromatin to accomplish these gene expression changes during cardiac hypertrophy and failure are largely unknown. We used a proteomics approach to identify proteins bound to cardiac chromatin and to quantify changes in their abundance during disease. Quantitative mass spectrometry and bioinformatics revealed that 366 of the chromatin-bound proteins detected in this study displayed altered expression in a mouse model of pressure overload cardiac hypertrophy and failure. This included the chromatin remodeling protein Nucleolin (Ncl), which exhibited increased association with chromatin in the hypertrophic heart. To examine its role in regulating cardiac morphology and function we performed morpholino based knockdown of Ncl in zebrafish embryos. Ncl knockdown promoted the expression of bmp4 (a fetal marker), inhibited normal cardiomyocyte differentiation and resulted in abnormal heart chamber formation and looping. Hearts in surviving fish exhibited functional deficits as measured by fluorescence imaging and line-scanning analysis. To investigate the actions of Ncl in the mammalian cardiomyocyte, knockdown was carried out in isolated rat ventricular myocytes using siRNA. Loss of Ncl induced heterochromatin formation (increased Histone H3 K9-trimethylation), suppressed rDNA transcription (52% decrease in pre-rRNA via qPCR) and promoted fetal gene expression (65% increase in ANF; 41% increase in β-MHC transcripts). Overall, this study identifies Ncl as a regulator of chromatin structure, cell growth via ribosome biogenesis and cellular plasticity in the cardiomyocyte.
Cost and Utilization Of Stored Autologous PBSC To Support Tandem ASCT In MM Patients In The Era Of Novel Agent Therapy
Authors: Colin Phipps, Michael L. Linenberger, Damian J. Green, M. Corinna Palanca-Wessels, Pamela S. Becker, Laura S. Connelly-Smith, Nicholas Burwick, Zandra K. Klippel, William I. Bensinger, Leona Holmberg, Edward N. Libby
Journal: Blood (2013)