tbuckley/cabot-search huggingface dataset:
Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury
Authors: Elena Arriazu, Xiaodong Ge, Tung-Ming Leung, Fernando Magdaleno, Aritz Lopategi, Yongke Lu, Naoto Kitamura, Raquel Urtasun, Neil Theise, Daniel J Antoine, Natalia Nieto
Journal: Gut (2016)

Liver fibrosis is associated with significant collagen-I deposition largely produced by activated hepatic stellate cells (HSCs); yet, the link between hepatocyte damage and the HSC profibrogenic response remains unclear. Here we show significant induction of osteopontin (OPN) and high-mobility group box-1 (HMGB1) in liver fibrosis. Since OPN was identified as upstream of HMGB1, we hypothesised that OPN could participate in the pathogenesis of liver fibrosis by increasing HMGB1 to upregulate collagen-I expression.Patients with long-term hepatitis C virus (HCV) progressing in disease stage displayed enhanced hepatic OPN and HMGB1 immunostaining, which correlated with fibrosis stage, whereas it remained similar in non-progressors. Hepatocyte cytoplasmic OPN and HMGB1 expression was significant while loss of nuclear HMGB1 occurred in patients with HCV-induced fibrosis compared with healthy explants. Well-established liver fibrosis along with marked induction of HMGB1 occurred in CCl4-injected OpnHep transgenic yet it was less in wild type and almost absent in Opn-/- mice. Hmgb1 ablation in hepatocytes (Hmgb1ΔHep) protected mice from CCl4-induced liver fibrosis. Coculture with hepatocytes that secrete OPN plus HMGB1 and challenge with recombinant OPN (rOPN) or HMGB1 (rHMGB1) enhanced collagen-I expression in HSCs, which was blunted by neutralising antibodies (Abs) and by Opn or Hmgb1 ablation. rOPN induced acetylation of HMGB1 in HSCs due to increased NADPH oxidase activity and the associated decrease in histone deacetylases 1/2 leading to upregulation of collagen-I. Last, rHMGB1 signalled via receptor for advanced glycation end-products and activated the PI3K-pAkt1/2/3 pathway to upregulate collagen-I.During liver fibrosis, the increase in OPN induces HMGB1, which acts as a downstream alarmin driving collagen-I synthesis in HSCs.
Government could fire and rehire consultants to introduce new contract, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

The government could fire and rehire consultants in order to move them on to a new contract, the BMA has said.

Delegates at the BMA’s annual UK consultants’ conference in London on 3 March heard that this could be one option considered by the government if consultants rejected its final contract offer.

The government has yet …
Improving Cancer Pain Control With NCCN Guideline-Based Analgesic Administration: A Patient-Centered Outcome
Authors: Nora Janjan
Journal: Journal of the National Comprehensive Cancer Network (2014)

Improving the control of cancer-related pain (CRP) is a clinical and ethical imperative. Clinical research has documented improved treatment tolerance and survival rates among patients with cancer who have effective pain control. Barriers to CRP control include inadequate patient and physician education. Meta-analyses of patient education studies correlate improvements in CRP control with improved communications with health care providers and the implementation of strategies that assist with adherence to medication schedules. These strategies build patient confidence, allowing better self-management of pain and reduced psychological consequences. For physicians, ample educational resources exist in CRP management. However, in both the inpatient and outpatient settings, compliance with NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain continues to be less than 70%, and more than one-third of patients continue to receive inadequate doses of analgesics. Patient-centered outcomes have become an integral end point in health policy, and the nation's medical training, research, and delivery systems are transforming to a value-based accreditation and reimbursement system. Pain control is a significant patient-centered outcome in cancer care, because pain adversely impacts function and affects all domains of quality of life. Agreement is clear on the value of health care interventions that relieve suffering from cancer pain and restore personal dignity.
Clinical Classification of Extent of Disease in Cancer of the Breast
Authors: Sidney J. Cutler, Sc.D, Max H. Myers
Journal: JNCI Journal of the National Cancer Institute (1967)

A series of 2,039 cases of breast cancer in women under 65 years of age was used for an empirical-statistical approach to the classification of extent of disease. Comparisons were made with the staging recommendations of an American and an international committee. The uses for such classification schemes by the clinician in assessing prognosis and deciding on a treatment plan are considered. It is suggested that the same treatment plan is not necessarily appropriate for all patients falling into the same prognostic class, because there is marked variation in the clinical characteristics of patients within a class.
Pharmacokinetic Characterisation Of Recombinant FXIII Across Age Groups In Patients With FXIII Subunit A Congenital Deficiency
Authors: Brigitte Brand-Staufer, Manuel Carção, Bryce A. Kerlin, Diane Nugent, Andrew Will, Michael Williams, Anders Rosholm, Mia Sandberg Lundblad
Journal: Blood (2013)
Urethan as a Carcinogen for the European Hamster2
Authors: Ulrich Mohr, Gerd Reznik, Hildegard Reznik-Schüller
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Urethan as a Carcinogen for the European Hamster Get access Ulrich Mohr, Ulrich Mohr Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerd Reznik, Gerd Reznik Search for other works by this author on: Oxford Academic PubMed Google Scholar Hildegard Reznik-Schüller Hildegard Reznik-Schüller 3Abteilung fur Experimentelle Pathologie, Medizinische Hochschule Hannover, 3000 Hannover-Kleefeld, KarlWiechert- Allee 9, West Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1359–1367, https://doi.org/10.1093/jnci/53.5.1359 Published: 01 November 1974 Article history Received: 21 May 1974 Accepted: 18 July 1974 Published: 01 November 1974
Infection with Mayaro virus in a French traveller returning from the Amazon region, Brazil, January, 2010
Authors: M C Receveur, M Grandadam, T Pistone, D Malvy
Journal: Eurosurveillance (2010)

Mayaro virus (MAYV) disease is a mosquito-borne zoonosis endemic in humid forests of tropical South America. MAYV is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. A French tourist developed high-grade fever and severe joint manifestations following a 15-day trip in the Amazon basin, Brazil, and was diagnosed with MAYV infection in January 2010. This case is the first reported in a traveller returning from an endemic South American country to Europe.
Capitation payments would be fairer
Authors: R V Millard
Journal: BMJ (1995)

EDITOR,--Jon S Dowell and colleagues' paper shows that generic substitution can be acceptable to patients but also shows the inequity of the budgeting process.1 The practice budget shown of £573802, or £89 per head, for 1993-4 seems astronomical. This compares with a projected spend in our fundholding practice of approximately £48.25 per head in 1994-5, with a budget allowance of approximately £50 per head. …
Buffered crystalloid solution shows no benefit over saline in critical care
Authors: Jacqui Wise
Journal: BMJ (2015)

Using a buffered crystalloid solution instead of saline in the intensive care unit (ICU) did not reduce the risk of acute kidney injury in critically ill patients, a double blind randomised trial published in JAMA has found.1

Isotonic 0.9% sodium chloride (saline) is the most commonly used intravenous fluid in much of the world. However, concerns have arisen that the high chloride content of saline could contribute to the development of acute kidney injury. An alternative to saline is …
Evaluation of Ceritinib-Treated Patients (Pts) with Anaplastic Lymphoma Kinase Rearranged (Alk+) Non-Small Cell Lung Cancer (Nsclc) and Brain Metastases in the Ascend-1 Study
Authors: A.T. Shaw, R. Mehra, D.S.W. Tan, E. Felip, L.Q. Chow, D.R. Camidge, J.F. Vansteenkiste, S. Sharma, T. De Pas, G.J. Riely, B. Solomon, J. Wolf, M. Thomas, M. Schuler, G. Liu, A. Santoro, M. Geraldes, A.L. Boral, A. Yovine, D. Kim
Journal: Annals of Oncology (2014)
The Pediatric Oncology Group experience with the international staging system criteria for neuroblastoma. Member Institutions of the Pediatric Oncology Group.
Authors: R P Castleberry, J J Shuster, E I Smith
Journal: Journal of Clinical Oncology (1994)

PURPOSE An international consensus on the criteria for surgicopathologic staging (INSS) of patients with neuroblastoma has been published, but has not been validated. A retrospective study was conducted to assess if the INSS definitions identified prognostic subsets of patients with neuroblastoma. PATIENTS AND METHODS The initial operative and pathology reports were reviewed from 675 patients on Pediatric Oncology Group (POG) #8104, a stage- and age-related treatment study that used the POG surgicopathologic staging system. RESULTS Of 596 eligible cases, there was concordance between the POG and INSS stages for the 193 patients with localized, resected disease (POG stage A), the 202 with distant metastases, the 51 with POG stage Ds (IVs) tumors, and 40 of the cases with grossly unresected, localized tumor without lymph node involvement (POG stage B). Of the remaining 19 patients with POG stage B tumors, five were INSS stage 2B and 14 INSS stage 3. All of the 91 cases with nonadherent, regional lymph node metastases (POG stage C) conformed to the definitions for INSS stage 2B (n = 42) or 3 (n = 49). In infants, there was no difference in event-free survival (EFS) among INSS stages 2A, 2B, or 3. In contrast, older children with INSS stage 3 disease had inferior EFS compared with INSS stage 2A or 2B tumors. CONCLUSION We conclude the following: (1) the INSS identifies distinct patient subsets, particularly in children; (2) infants remain a favorable group, regardless of INSS/POG stage; and (3) the INSS deserves further prospective study especially in the light of recent biologic prognostic variables.
ART1, an extracellular ADP-ribosyltransferase, is over-expressed in non-small cell lung cancer and facilitates cancer cell survival by immune-mediated mechanisms
Authors: Chuang Chen, Christopher Agrusa, Abu Nasar, Esi Kajno, Nasser K. Altorki, Timothy E. McGraw, Brendon M. Stiles
Journal: Journal of Thoracic Oncology (2016)
Origin of Nuclei in Spontaneous HeLa Cell Chromosome Pulverization&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F. J. O'Neill, C. P. Miles
Journal: JNCI Journal of the National Cancer Institute (1971)

Spontaneous chromosome pulverization of polyploid HeLa cells is described. Pulse-chase experiments with 3H-thymidine indicate asynchrony between the normal (intact) and pulverized chromosomes, with the pulverized chromosomes beginning DNA synthesis after the normal chromosomes. Other experiments were designed to determine whether the polyploid cells containing the pulverized material arose by cell fusion or by failure of cytokinesis to occur. Equal numbers of HeLa cells prelabeled with 3H-thymidine and unlabeled HeLa cells were propagated together for 12 and 24 hours. Chromosome pulverizations were then examined by autoradiography for the presence of labeling patterns resulting from cell fusion. The results showed no evidence for cell fusion, and apparently these polyploid cells have arisen through some mechanism which allows nuclear division to occur without cytokinesis. However, the results of similar experiments performed on human diploid cell lines, but with the addition of Sendai virus, provided direct evidence that: 1) Chromosome pulverization in virus-treated cultures occurred in fused cells, and 2) this method of growing labeled and unlabeled cells together could detect such fused cells.
Phase I Trial of Multiple Cycles of High-Dose Chemotherapy Supported by Autologous Peripheral-Blood Stem Cells
Authors: Russell J. Schilder, Steven Johnson, James Gallo, Scott Kindsfather, Barbara Rogers, Michael A. Bookman, Michael M. Millenson, Matthew Boente, Norman Rosenblum, Samuel Litwin, Robert F. Ozols
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m 2 ) with PBSC and GM-CSF repeated every 28 days. RESULTS: Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicitieswere dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m 2 ). The relationship of target AUC to measured AUC was linear (r 2 = .29; P = .0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION: Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m 2 ) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.
Abstract P344: Hypothetical Interventions on Fish Consumption in Mid and Later Life and the Risk of Coronary Heart Disease in Women: An Application of the Parametric G-formula
Authors: Martin Lajous, Walter C Willett, James Robins, Dariush Mozaffarian, Miguel A Hernan
Journal: Circulation (2012)

Background_Long-term randomized trials of interventions on fish and primary prevention of coronary heart disease (CHD) are unavailable. The parametric g-formula uses observational data to estimate the effect of changes on fish consumption that would have been observed under hypothetical interventions. Methods and Results_Among 53,799 women from the Nurses’ Health Study aged 39-67 and free of CHD at baseline in 1986, 1,891 developed incident CHD (1,145 non fatal, 830 fatal) by 2008. Women provided information on risk factors and medical conditions every 2 years and on diet every 4 years. We used the parametric g-formula to evaluate hypothetical interventions from baseline forward on fish intake. Specifically, we estimated the CHD risks if all women had changed their fish intake to zero servings per week, and if all women had changed their fish intake to at least 1, 2, 3 and 5 servings per week during the entire follow-up. We adjusted for age and family history of CHD, and for baseline and time-varying menopausal status, use of oral contraceptives, postmenopausal hormone therapy, aspirin, multivitamin and vitamin E supplements, diabetes, hypertension, hypercholesterolemia, stroke, angina or CABG, BMI, physical activity, smoking and intake of calories, trans fatty acids, cereal fiber and red meat. The estimated CHD risk was 4.13 if fish intake had been changed to zero after 1986, and 3.77, 3.53, 3.32 and 3.35, if all women had changed their fish intake to at least 1, 2, 3 and 5 servings per week, respectively. Compared with changing fish intake to zero, the risk ratio of CHD was 0.85 (95% CI 0.75, 0.91) for changing intake to at least 2 servings/week, and 0.80 (95% CI 0.71, 0.97) for changing intake to at least 3 servings. This estimated protective effect of increased fish consumption was restricted to fatal CHD. Results were not appreciably altered when we specified that red meat was replaced by fish intake. Conclusion_Our results suggest that increasing fish consumption in mid or later life may lower the 22-year risk of CHD in women by 20%. Using the parametric g-formula allowed to explicitly specify hypothetical interventions to evaluate the effectiveness of diet change over a long period. Like all observational estimates, the parametric g-formula estimates may be affected by unmeasured confounding, model misspecification, and measurement error.
Harnessing Big Data for Systems Pharmacology
Authors: Lei Xie, Eli J. Draizen, Philip E. Bourne
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and actionable. The current explosions in genomics and other omics data, as well as the tremendous advances in big data technologies, have already enabled biologists to generate novel hypotheses and gain new knowledge through computational models of genome-wide, heterogeneous, and dynamic data sets. More work is needed to interpret and predict a drug response phenotype, which is dependent on many known and unknown factors. To gain a comprehensive understanding of drug actions, SPM requires close collaborations between domain experts from diverse fields and integration of heterogeneous models from biophysics, mathematics, statistics, machine learning, and semantic webs. This creates challenges in model management, model integration, model translation, and knowledge integration. In this review, we discuss several emergent issues in SPM and potential solutions using big data technology and analytics. The concurrent development of high-throughput techniques, cloud computing, data science, and the semantic web will likely allow SPM to be findable, accessible, interoperable, reusable, reliable, interpretable, and actionable.
A head-to-head comparison of Mammaprint and Oncotype Dx: A McGill University Health Center Experience.
Authors: Ralph Maroun, Ramy Saleh, Jamil Asselah, Atilla Omeroglu, Altinel Gulbeyaz, Sarkis H. Meterissian, Nathaniel Bouganim
Journal: Journal of Clinical Oncology (2015)

11017 Background: The Objective of our study was to investigate the concordance of patient results from a single university centre tested with the 21-gene recurrence score assay, Oncotype DX (ODX) when compared to the 70-gene signature Mammaprint (MP), the 80 gene signature of BluePrint (BP) and TargetPrint (TP). Methods: Eighty-six consecutive patient-slides node negative hormone positive breast cancer tissue tested with the ODX were enrolled. Based on the ODX recurrence scores (RS) patients were placed either on Chemotherapy and hormonal therapy or hormonal therapy alone. MP was performed on all of the slides previously tested with ODX, and results were reported as either Low or high recurrence risk and were compared with those of the ODX. Results: Of the 50 ODX low RS cases, 33 were low risk by MP (66 % agreement) and of the 9 ODX high RS, 7 were high risk by MP (78 % agreement). Of ODX intermediate risk cases (27), 14 of were MP Low risk (52 %), (48 %) 13 were MP high risk. Of BP low risk luminal tumors, 33/49 (67%) were ODX low, 14/49 (29%) ODX intermediate, and 2/49 (4%) ODX high risk (Table). BP class was correlated with ER, PR and HER2 results. Overall agreement between clinical ER, PR, HER2 (IHC+FISH) results with TP results were 98% (81/83), 83% (69/83), 99% (82/83), and percent positive agreement for HER2 was 0/1 (of unequivocally HER2 positive cases identified correctly by TP). Conclusions: Results from our institution show that they are real differences in risk assignments between MP and ODX that may affect treatment decisions. There was close correlation between pathologic variables and MP and BP. These results underscore the need for a proper validation of the ODX and MP genetic signatures with outcomes in order to avoid misclassification of both low and high risk patients. ODx vs. MP. Oncotype Mammaprint Blueprint High intermediate Low Total High risk MP Basal-like 0 0 0 0 ERBB2 1 1 0 2 Luminal-like 6 11 18 35 High risk total 7 12 18 37 Low risk MP Basal-like 0 0 0 0 ERBB2 0 0 0 0 Luminal-like 2 14 33 49 Low risk total 2 14 33 49 Grand total 10 25 52 86
ESGE/ESGENA Technical Note on Cleaning and Disinfection
Authors: J.-F.  Rey, A.  Kruse
Journal: Endoscopy (2003)

The ESGE together with ESGENA and the biomedical industry met under the auspices of the ESGE Guidelines Committee to discuss and propose this technical note on cleaning and disinfection in order to clarify this technically difficult topic for the daily user.
Questions for esophageal stents treatment in acute refractory esophageal variceal bleeding
Authors: Chenguang Dai, Lili Zhao, Li Liu, Xiang Wang, Min Wang, Zhining Fan
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: The prospective study by Escorsell et al.1 demonstrated that self‐expandable, covered, esophageal metal stents (SX‐ELLA Danis; Ella‐CS, Hradec Kralove, Czech Republic) have greater efficacy and fewer serious adverse events in controlling acute esophageal variceal bleeding compared with balloon tamponade. If stents would be the primary choice for refractory esophageal variceal bleeding, some questions need to be further clarified. According to reports,2 open esophageal stents located across the esophagogastric junction often have caused gastroesophageal reflux, which is associated with a risk of aspiration. In this research, no gastroesophageal reflux was mentioned. Zehetner et al. also reported stent efficacy for acute bleeding from esophageal varices,5 with the patient's upper body positioned slightly upright to reduce the risk of reflux and aspiration. In clinics, some esophageal stents have been improved with an antireflux design to control stent‐related reflux. Therefore, some questions need to be answered: How many patients in the stent group suffered from gastroesophageal reflux? Did any aspiration occur? How did researchers deal with such issues: by changing the body position or applying some antireflux devices? In the future, more studies will be needed for considering the antireflux issue, including implantation protocol and stent design for controlling acute refractory esophageal variceal bleeding.
Carcinogenicity of Nitrosotrialkylureas in Fischer 344 Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: W Lijinsky, M D Reuber, B N Blackwell
Journal: JNCI Journal of the National Cancer Institute (1980)

Three nitrosotrialkylureas were administered to female F344 rats as approximately 1-mM solutions in drinking water. Nitrosotrimethylurea, given for 47 weeks, gave rise to astrocytomas of the brain and tumors of the forestomach; nitrosotriethylurea induced a high incidence of adenocarcinomas of the breast and uterus and tumors of the forestomach. Nitrosomethyldiethylurea induced almost exclusively a high incidence of both astrocytomas of the brain and tumors of the spinal cord.