tbuckley/cabot-search huggingface dataset:
Strong support for strike sends clear message to government, says BMA
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Tens of thousands of junior doctors turned out to express their unhappiness about proposed changes to their contract on the first day of industrial action by the medical profession for 40 years, on Tuesday 12 January.

The atmosphere among some 38 000 junior doctors on picket lines across England was described as one of solidarity and good natured, with strong public support. The walkout is backed by two thirds of the public (66%), showed the results of an Ipsos MORI poll for the Health Service Journal.

Johann Malawana, chair of the BMA’s Junior Doctors Committee, sounded a note of regret that negotiations with the government had failed to reach a resolution. He declared Tuesday “the saddest day in our profession’s recent …
On the Absence of Calreticulin (CALR) Mutations in Chronic Myeloprolierative Neoplasms (MPNs) with Splanchnic Venous Thrombosis (SVT): Experience from a Single Institution
Authors: Bruno Martino, Corrado Mammì, Claudia Labate, Martino Enrica Antonia, Francesca Ronco, Anna Grazia Recchia, Domenica Ielo, Caterina Alati, Esther Oliva, Carmelo Laganà, Fortunato Morabito
Journal: Blood (2014)
Abstract 18113: Stress and Uncertainty as Perceived by Parents of Infants Discharged following the Norwood Operation
Authors: Jo Ann Nieves, E Marsha Elixson, Sandra Staveski, Jennifer Strawn, Cathy Smith, Yu Wang, Eileen King, Karen Uzark
Journal: Circulation (2010)

Caregivers of infants with complex single ventricle may experience significant stress related to uncertainty concerning their infant9s heart condition and care needs following the Norwood operation. To better understand the stress experienced by these families, we assessed parental uncertainty stress and its relationship to patient characteristics/outcomes.   Methods:  As part of a multicenter study of feeding practices and weight gain, parents completed the Mishel Parental Perception of Uncertainty scale (PPUS) pre-discharge (n=99) and at 4 wks (n=78) and 12 wks (n=63) post discharge (DC). The PPUS contains 4 subscales: Ambiguity, Lack of Clarity, Lack of Information (Info), and Unpredictability, with a 5-point Likert response format.   Results:  With higher scores = higher uncertainty, PPUS scores were highest related to Unpredictability at all time points (mean/SEM= 3.14/.07 pre DC, 2.92/.07 at 4 wks, 2.81/.10 at 12 wks) and lowest related to Lack of Info (mean/SEM =1.67/.05, 1.68/.06 at 4 wks, 1.69/.06 at 12 wks). There was no significant change in PPUS total or subscale scores over time except Unpredictability which significantly decreased from pre-DC to 4 wks post DC (p  s  = -.39, p=.01.   Conclusion:  Parents of infant survivors following Norwood operation experience persistent stress following DC, unrelated to HLOS, though perceived unpredictability decreases following DC. Parents of orally fed infants perceived greater unpredictability pre-discharge. Infants of more informed parents had better weight gain. Surveillance and increased communication of information, especially related to feeding in this study, may decreased parental uncertainty stress and assist parents in caring for their infants following Norwood operation.
Frozen faecal matter works as well as fresh for transplantation in<i>C difficile</i>patients
Authors: Jacqui Wise
Journal: BMJ (2016)

Restoring protective colonic microbiota in patients with recurrent Clostridium difficile infection can be done just as well with transplanted frozen and then defrosted faecal matter as with fresh stools, a study published in JAMA has shown.1 Using frozen faecal microbiota transplantation would remove many of the logistical burdens that clinicians face when preparing fresh material.

Since the emergence of hypervirulent strains in the early 2000s, …
A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505).
Authors: Ryo Kitagawa, Noriyuki Katsumata, Taro Shibata, Toru Nakanishi, Sadako Nishimura, Kimio Ushijima, Masashi Takano, Toyomi Satoh, Hiroyuki Yoshikawa, Toshiharu Kamura
Journal: Journal of Clinical Oncology (2012)

5006 Background: TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This multicenter phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is current standard chemotherapy for stage IVB or recurrent cervical cancer. Methods: Patients (pts) with stage IVB or recurrent cervical cancer; not amenable to curative therapy; 0-1 prior platinum; no prior taxanes; were randomized with minimization method to either TP (T 135 mg/m 2 24h d1 + P 50 mg/m 2 2h d2) or TC (T 175 mg/m 2 3h d1 + C AUC5 1h d1), both for maximum 6 cycles every 21 days. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), toxicities, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The trial was powered at least 70% to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS, and the planned sample size was 250 pts with one-sided alpha 5%. HR is estimated by a stratified Cox regression. Results: From 2/06 to 11/09, 253 pts were enrolled. 71% pts of TP arm and TC arm each received 6 cycles. Median follow-up is 17.4 mo. Results are as below. As an alpha level for an interim analysis was less than 0.0001, significance level for the final analysis is approximately 5% even after the multiplicity adjustment. Conclusions: This first randomized controlled trial comparing carboplatin doublet with cisplatin doublet showed significant non-inferiority of TC in terms of OS. More feasible and less toxic TC can be recommended as the new standard treatment for stage IVB or recurrent cervical cancer. [Table: see text]
Phase I Evaluation of Sequential Doxorubicin Gemcitabine Then Ifosfamide Paclitaxel Cisplatin for Patients With Unresectable or Metastatic Transitional-Cell Carcinoma of the Urothelial Tract
Authors: Paul M. Dodd, John A. McCaffrey, Susan Hilton, Madhu Mazumdar, Harry Herr, W. Kevin Kelly, Evelyn Icasiano, Mary G. Boyle, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This phase I trial sought to evaluate the toxicity of and determine the maximum-tolerated dose (MTD) for the two-drug regimen doxorubicin and gemcitabine (AG) followed by the three-drug regimen of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with unresectable or metastatic transitional-cell carcinoma. PATIENTS AND METHODS: Patients received AG every other week for six cycles followed by ITP every 3 weeks for four cycles. Five AG dose levels were investigated, up to doxorubicin 50 mg/m 2 and gemcitabine 2,000 mg/m 2 , to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m 2 (days 1 to 3); paclitaxel 200 mg/m 2 (day 1); and cisplatin 70 mg/m 2 (day 1). Granulocyte colony-stimulating factor was given between all cycles of therapy. RESULTS: Fifteen patients enrolled onto this phase I trial. AG was well tolerated at all dose levels, with no grade 3 or 4 myelosuppression. Toxicity experienced with ITP included grade 3 and 4 granulocytopenia in four patients and grade 3 nausea/vomiting in three patients. No grade 3 and 4 neurotoxicity was observed. Eight of 14 assessable patients experienced a major response to AG, including five of six patients treated at the two highest AG dose levels. After completion of AG-ITP, nine of 14 assessable patients had a major response (three complete responses and six partial responses). CONCLUSION: AG is a well-tolerated and active regimen. Sequential chemotherapy with AG-ITP is also well tolerated, and phase II investigation at the highest dose level is ongoing.
Gene expression in primary and metastatic kidney cancer to discover drivers of metastasis and targets for drug development
Authors: Amy Zhao, Arjun Guru, Sonpavde Guru, Eddy Yang, Yufeng Li
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts An estimated 63,920 cases of kidney cancer will occur in the USA in 2015, and about 13,860 deaths will occur. The incidences of kidney cancer has steadily increased by 2-4% each year. Currently high dose IL (Interleukin)-2, VEGF (vascular endothelial growth factor) inhibitors, and
Ferritin in Synovial Cells in Patients with Rheumatoid Arthritis
Authors: K. D. Muirden
Journal: Annals of the Rheumatic Diseases (1966)

cases to be described the period of anoxia produced by the tourniquet was kept to within 2 minutes in Cases 1 and 3, and in Case 2 a tourniquet was not used at all.After removal the tissue was immediately fixed in an ice-cold solution of 1 per cent.osmium tetroxide in veronal acetate buffer, pH 7-2 to 7 4, to which was added 0 045 g. sucrose per ml.fixative.The tissue was sliced into small pieces and transferred to further fixative.After fixation 387
Effect of Prophylactic Treatment with Intravesical Epirubicin on Recurrence of Superficial Bladder Cancer—The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG):
Authors: Masao Kuroda, Tadao Niijima, Toshihiko Kotake, Hideyuki Akaza, Shiro Hinotsu
Journal: European Urology (2004)
Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice
Authors: Karim Gariani, Keir J. Menzies, Dongryeol Ryu, Casey J. Wegner, Xu Wang, Eduardo R. Ropelle, Norman Moullan, Hongbo Zhang, Alessia Perino, Vera Lemos, Bohkyung Kim, Young‐Ki Park, Alessandra Piersigilli, Tho X. Pham, Yue Yang, Chai Siah Ku, Sung I. Koo, Anna Fomitchova, Carlos Cantó, Kristina Schoonjans, Anthony A. Sauve, Ji‐Young Lee, Johan Auwerx
Journal: Hepatology (2015)

With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high‐fat high‐sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD + ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD + repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD + biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1‐ and SIRT3‐dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic β‐oxidation and mitochondrial complex content and activity. The cell‐autonomous beneficial component of NR treatment was revealed in liver‐specific Sirt1 knockout mice ( Sirt1hep−/− ), whereas apolipoprotein E ‐deficient mice ( Apoe −/− ) challenged with a high‐fat high‐cholesterol diet affirmed the use of NR in other independent models of NAFLD. Conclusion: Our data warrant the future evaluation of NAD + boosting strategies to manage the development or progression of NAFLD. (H epatology 2016;63:1190–1204)
Risk factors for PTSD and other diagnoses in a general sample of Vietnam veterans
Authors: B L Green, M C Grace, J D Lindy, G C Gleser, A Leonard
Journal: American Journal of Psychiatry (1990)

This study examined the contribution of premilitary, military, and postmilitary risk factors to posttraumatic stress disorder (PTSD) and other postwar diagnoses in a sample of Vietnam veterans. PTSD was explained primarily by war stressors, including threat to life and exposure to grotesque death, but premilitary and postmilitary factors also contributed to the likelihood of a current diagnosis of PTSD. Panic disorder was also highly predicted by war experiences, whereas prewar functioning played a stronger role in several non-PTSD diagnoses. The study supported the notion that PTSD is specifically linked to intense stressors. Mechanisms for interactions among risk factors are discussed.
Novel Antiandrogen Arn-509 in High-Risk Non-Metastatic (M0) Castration-Resistant Prostate Cancer (Crpc)
Authors: M.R. Smith, E.S. Antonarakis, C.J. Ryan, W. Berry, N.D. Shore, G. Liu, J. Alumkal, C. Higano, E. Chow-Maneval, R. Bandekar, C. De Boer, M. Todd, M. Yu, D.E. Rathkopf
Journal: Annals of Oncology (2014)
Viral epidemiology and severity of respiratory infections in infants in 2009-2010 winter: A prospective study in Basse-Normandie
Authors: Carmen Laurent, Audrey Dugué, Jacques Brouard, Julia Dina, Astrid Vabret
Journal: European Respiratory Journal (2011)

Background:  Symptoms are not specific of the causal virus. The new pandemic influenza virus A H1N1v2009 was feared to cause particularly severe outcomes, especially in infants.   Aims and objectives:  The objective was to evaluate the impact of H1N1v2009 on the viral epidemiology, the clinical presentation and the severity of respiratory infections in infants.   Methods:  This prospective epidemiological study included all infants aged less than 2 years presenting with respiratory symptoms, from November 2009 to April 2010, at the pediatric emergency department of the University Hospital of Caen, Basse-Normandie, France, whether they were inpatients or outpatients. A nasal swab was taken for viral detection and analyzed by immunofluorescence and, if negative or influenzaA, polymerase chain reaction. Severe respiratory infection was defined by a score of respiratory severity.   Results:  1021 infectious episodes with a respiratory sample met inclusion criteria. 834 samples (81.7%) were positive. The four viruses with the highest incidence were the Respiratory Syncytial virus (RSV) (34.28%), the rhinoviruses (23.90%), the coronaviruses (9.30%) and H1N1v2009 (7.74%). 28.61% of infections were severe, and more frequent in infants with risk factors. H1N1v2009 infections had a low risk of severe respiratory disease (OR = 0.15) and hospitalization (OR = 0.40) compared to the other viruses. RSV infections had a high risk of respiratory severity (OR = 7.85) and were responsible for 71.43% of admissions to the intensive care unit.   Conclusions:  Despite the modest impact of H1N1v2009 observed in this study, further surveillance is needed to detect virological factors increasing severity.
Tyrosinase activation of acetylsalicylic acid (Aspirin) leads to acetylsalicylic acid selective toxicity towards melanocytic melanoma cell lines
Authors: Nikhil Vad, Garret Yount, Majid Moridani
Journal: Cancer Research (2008)

1287  Purpose: In the current work, we investigated the biochemical toxicity of acetylsalicylic acid (ASA; Aspirin) in human melanoma cell lines using tyrosinase enzyme as a selective molecular cancer therapeutic target. Because tyrosinase is found abundantly and selectively in melanoma cells we hypothesized that the intracellular tyrosinase enzyme can selectively bioactivate ASA, as a prodrug, to quinone intermediate species, which in turn can lead to selective toxicity against melanoma. Experimental procedures: UV-VIS spectra was used to investigate the enzymatic oxidation of ASA by tyrosinase enzyme. GSH depletion was used to measure the extent of ASA metabolism by tyrosinase and rat liver microsomes. The toxicity of ASA was investigated in four melanocytic melanoma cell lines (which express functional tyrosinase), and in four non-melanoma cell lines and one amelanocytic melanoma cell line (which do not express functional tyrosinase) using MTT assay. The biochemical mechanism of ASA was investigated in human SK-MEL-28 melanocytic melanoma cell line, which expresses functional tyrosinase, using a number of modulators. Results: At 2h, ASA was oxidized 44% by tyrosinase. Ascorbic acid and NADH, quinone reducing agents, were significantly depleted during the enzymatic oxidation of ASA by tyrosinase to quinone. The IC50 (48h) of ASA and salicylic acid towards SK-MEL-28 cells were determined to be 100 μM and 5.2 mM, respectively. ASA at 100 μM was selectively toxic towards human SK-MEL-28, MeWo, and SK-MEL-5 and murine B16-F0 melanocytic melanoma cell lines. However, ASA was not significantly toxic towards human C32 amelanocytic melanoma cell line and human BJ, SW-620, Saos and PC-3 non-melanoma cells (which do not express tyrosinase enzyme). Dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depletory agent, increased ASA toxicity towards SK-MEL-28 cells indicating quinone formation and intracellular GSH depletion played important mechanistic roles in ASA induced melanoma toxicity. Ascorbic acid, a quinone reducing agent, and GSH, an antioxidant and quinone trap substrate, prevented ASA cell toxicity. Trifluoperazine and cyclosporine A, inhibitors of permeability transition pore in mitochondria, prevented ASA toxicity. ASA caused time- and dose-dependent decline in intracellular GSH concentration, that preceded cell toxicity. ASA also led to reactive oxygen species (ROS) formation in melanoma cells which was exacerbated by dicoumarol and 1-bromoheptane. Conclusion: Our investigation suggests that ASA as a prodrug was selectively bioactivated by tyrosinase to reactive quinones, and that quinone species, intracellular GSH depletion, ROS formation and mitochondrial toxicity significantly contributed towards ASA selective toxicity in melanoma cells.
Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements
Authors: FG Behm, FO Smith, SC Raimondi, CH Pui, ID Bernstein
Journal: Blood (1996)
Organ-Independent Prediction of Brca1 Mutation-Like Status Based on Copy Number Gains and Losses in Breast and Ovarian Cancer
Authors: P. Schouten, D.J. Vis, E. van Dijk, C.H. van Deurzen, A. Jager, E.M. Berns, H.H. van Boven, H. Hereditary Breast, M. Rookus, P.M. Nederlof, L.F. Wessels, S. Linn
Journal: Annals of Oncology (2014)
Relevant prognostic markers involved in apoptosis in colorectal cancer
Authors: M. Gasser, M. Bueter, M. Grimm, S. Hom, M. Koenigshausen, A. Thalheimer, S. Mueller, A. Thiede, H.-J. Gassel, D. Meyer, A. M. Waaga-Gasser
Journal: Journal of Clinical Oncology (2005)

9662 Background: One of the main goals in cancer therapy is the detection of markers enabling a prognosis before therapy in patients with cancer. In addition, there are no suitable markers for the detection of colorectal cancer so far. The aim of this study was to identify clinical relevant markers, which are involved in the apoptosis of tumor cells. Methods: 81 patients operated with curative intent were included and compared according to their stage (UICC I: 21%, II: 25.9%, III: 23.5%, IV: 29.6%). Assessment of different markers for (anti)apoptosis, tumor suppressor gene p53 and T-cell subpopulations were performed using immunohistological doublestaining and Real Time PCR. The results were correlated with the relevant clinical and histopathological data of our clinical database. Results: In contrast to bcl-xL (UICC I/II: 77.8%, III/IV: 63.6%), bcl-2 was weakly detected in all patients independent of their stage. The expression of Fas/FasL, TRAIL/TRAILII receptor, and TGF-β/TGF-β receptor II (DR4) was dependent on the stage of the patients (Fas/FasL: UICC I/II 77.8%, III/IV 45.5%; TRAIL/TRAILII R: I/II 33.3%, III/IV 36.4%; TGF-β/TGF-β RII: I/II 34.4%, III/IV 63.6%). Moreover, a significant increase of FasL expression was detected on tumor cells from UICC III and IV patients compared with their Fas expression (p53/FasL: UICC I/II 22.2%, III/IV 50% vs. p53/Fas: UICC I/II 55.5%, III/IV 9.1%). During the progressive course of disease an increased number of infiltrating CD4+ (T helper cells), but not of CD8+ (cytotoxic T cells) or NK cells (natural killer), was detected in the tumor (p53/CD4: UICC I/II 18.2%, ÍII/IV 33.3%; p53/CD8: I/II 55,5%, III/IV 11,1%; p53/NK: I/II 45,6%, III/IV 18,2%). In addition, a marked decrease in the FasL expression was observed in CD8+ (4-fold) and NK cells (99%). These results were confirmed by the molecular analysis of Fas, FasL, p53, bcl-2, CD4, CD8, NK, and TGF-β. Conclusions: This study indicates that the tumor become less vulnerable to cytotoxic and NK cell response during tumor progression. The tumor develops a mechanism to protect from immunological killing. Moreover, high expression of TGF-β receptor II and p53 in the primary tumor correlates with the progressive course of disease and tumor relapses in these patients. No significant financial relationships to disclose.
Sibling Comparisons and Confounding in Autism Epidemiological Studies
Authors: Diana E. Schendel, Erik Parner
Journal: JAMA Psychiatry (2016)

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Abstract 10999: Center for Medicare and Medicaid Services Reimbursement Criteria Concordant Primary Prevention ICD Implantation in the Outcomes Among Veterans with Implantable Defibrillators (OVID) Registry
Authors: David F Katz, Cara N Pellegrini, Paul A Heidenreich, Edmund C Keung, Pamela Peterson, John S Rumsfeld, Barry M Massie, Paul D Varosy
Journal: Circulation (2012)

Introduction: Numerous trials have led to the establishment of evidence-based Centers for Medicare and Medicaid Services (CMS) reimbursement criteria for the implantation of cardioverter-defibrilla...
Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study
Authors: Neal D Shore, Simon Chowdhury, Arnauld Villers, Laurence Klotz, D Robert Siemens, De Phung, Steve van Os, Nahla Hasabou, Fong Wang, Suman Bhattacharya, Axel Heidenreich
Journal: The Lancet Oncology (2016)