tbuckley/cabot-search huggingface dataset:
Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.
Authors: H Joensuu, K Holli, M Heikkinen, E Suonio, A R Aro, P Hietanen, R Huovinen
Journal: Journal of Clinical Oncology (1998)

PURPOSE We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS Patients in the single-agent arm (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2 three times per week (CEF) followed by M 8 mg/m2 plus vinblastine (V) 6 mg/m2 every 4 weeks. Exclusion criteria included age greater than 70 years, World Health Organization (WHO) performance status greater than 2, prior chemotherapy for metastatic disease, and presence of liver metastases in patients younger than 50. RESULTS An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity was less in the single-agent arm and quality-of-life (QOL) analysis favored the single-agent arm. No significant difference in time to progression or survival was found between the two arms. Similarly, no difference in survival was found when the patients who received both the planned first-and second-line treatments were compared or when survival was calculated from the beginning of the second-line therapy. CONCLUSION Patients treated with single-agent E followed by single-agent M had similar survival, but less treatment-related toxicity and better QOL as compared with those treated with CEF followed by MV.
Long-Term Artificial Selection Reveals a Role of TCTP in Autophagy in Mammalian Cells
Authors: Ke Chen, Chunhua Huang, Jia Yuan, Hanhua Cheng, Rongjia Zhou
Journal: Molecular Biology and Evolution (2014)

Understanding genomic variation and detecting selection signatures in a genome under selection have been great challenges for a century. Activation, development/exhaustion of primordial follicles in mammalian ovary determines reproductive success, menopause/end of female reproductive life. However, molecular mechanisms underlying oogenesis, particularly under artificial selection, are largely unknown. We report that a proteome-wide scan for selection signatures in the genome over 9,000 years of artificial pressure on the ovary revealed a general picture of selection signatures in the genome, especially genomic variations through artificial selection were detected in promoter and intron regions. Crossbreeding between domestic and wild species results in more than half of the protein spots exhibiting heterosis. Translationally controlled tumor protein (TCTP) is upregulated by artificial selection and positively regulates autophagy through the AMP-activated protein kinase pathway. Notably, TCTP interacts with ATG16 complex. In addition to cytoplasmic autophagy, nucleophagy occurs in the nuclei of granulosa and cumulus cells in ovaries, indicating an importance of the nuclear material for degradation by nucleophagy. Our findings provide insight into cellular and molecular mechanisms relevant for improvement of ovary functions, and identify selection signatures in the genome for ovary function over long-term artificial selection pressure.
Retrospective cohort study of false alarm rates associated with a series of heart operations: the case for hospital mortality monitoring groups
Authors: Jan Poloniecki, Charalambos Sismanidis, Martin Bland, Paul Jones
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To examine the efficacy of different methods of detecting a high death rate and determining whether an increase in deaths after heart transplantation could be explained by chance. <b>Design</b> Retrospective analysis of deaths after heart transplantation. Seven methods were used: mortality above national average, mortality excessively above national average, test of moving average mortality, test of number of consecutive deaths, sequential probability ratio test (SPRT), cusum graph with v-mask, and CRAM chart. The national average mortality was not available and a rate of 15% was used instead as the benchmark. <b>Setting</b> Regional cardiothoracic unit. <b>Participants</b> All 371 patients who received a heart transplant in the programme, 1986-2000. <b>Main outcome measures</b> 30 day survival after transplantation. <b>Results</b> All methods provided evidence that the 30 day mortality had been high at some stage. The probability that the finding was a false positive depended on which test was used. At the end of the series the average mortality, sequential probability ratio, and cusum tests indicated a level of deaths higher than the benchmark while the remaining four tests yielded negative results. <b>Conclusions</b> If the decision to test for outlying mortality is made retrospectively, in the light of the data, it is not possible to determine the false positive rate. Prospective on-site mortality monitoring with the CRAM chart is recommended as this method can quantify the death rate and identify periods when an audit of cases is indicated, even when data from other institutions are not available. A hospital mortality monitoring group can routinely monitor all deaths in the hospital, by specialty, using hospital episode statistics (HES) data and appropriate statistical methods.
A comparison of some force-interval relations in rat, hedgehog, and human cardiac preparations
Authors: P ARLOCK, B LIU, B WOHLFART, B W JOHANSSON
Journal: Cardiovascular Research (1988)

Journal Article A comparison of some force-interval relations in rat, hedgehog, and human cardiac preparations Get access P ARLOCK, P ARLOCK From the Experimental Electrocardiology, Departments of Zoophysiology, Pharmacology and Clinical Physiology, University of lund, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar B LIU, B LIU From the Experimental Electrocardiology, Departments of Zoophysiology, Pharmacology and Clinical Physiology, University of lund, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar B WOHLFART, B WOHLFART From the Experimental Electrocardiology, Departments of Zoophysiology, Pharmacology and Clinical Physiology, University of lund, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar B W JOHANSSON B W JOHANSSON From the Experimental Electrocardiology, Departments of Zoophysiology, Pharmacology and Clinical Physiology, University of lund, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 601, https://doi.org/10.1093/cvr/22.8.601 Published: 01 August 1988
Cost-Effectiveness of Prevention and Treatment of the Diabetic Foot
Authors: Monica Maria Ortegon, William Ken Redekop, Louis Wilhelmus Niessen
Journal: Diabetes Care (2004)

To estimate the lifetime health and economic effects of optimal prevention and treatment of the diabetic foot according to international standards and to determine the cost-effectiveness of these interventions in the Netherlands.A risk-based Markov model was developed to simulate the onset and progression of diabetic foot disease in patients with newly diagnosed type 2 diabetes managed with care according to guidelines for their lifetime. Mean survival time, quality of life, foot complications, and costs were the outcome measures assessed. Current care was the reference comparison. Data from Dutch studies on the epidemiology of diabetic foot disease, health care use, and costs, complemented with information from international studies, were used to feed the model.Compared with current care, guideline-based care resulted in improved life expectancy, gain of quality-adjusted life-years (QALYs), and reduced incidence of foot complications. The lifetime costs of management of the diabetic foot following guideline-based care resulted in a cost per QALY gained of < 25,000 US dollars, even for levels of preventive foot care as low as 10%. The cost-effectiveness varied sharply, depending on the level of foot ulcer reduction attained.Management of the diabetic foot according to guideline-based care improves survival, reduces diabetic foot complications, and is cost-effective and even cost saving compared with standard care.
Response to comment on Imamura et al. Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes. Metabolism 2014;63(11):1432–8
Authors: Satoshi Imamura, Tomoaki Morioka, Yuko Yamazaki, Ryutaro Numaguchi, Hiromi Urata, Koka Motoyama, Katsuhito Mori, Shinya Fukumoto, Tetsuo Shoji, Masanori Emoto, Masaaki Inaba
Journal: Metabolism (2014)
Susceptibility to air pollution in elderly males and females
Authors: H. M. Boezen, J. M. Vonk, S. C. van der Zee, J. Gerritsen, G. Hoek, B. Brunekreef, J. P. Schouten, D. S. Postma
Journal: European Respiratory Journal (2005)

It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex. Diary data on lower and upper respiratory symptoms (LRS and URS, respectively), cough, and morning and evening peak expiratory flow (PEF) were collected in 327 elderly patients (50–70 yrs) for a period of 3 months. Acute effects of particulate matter with a diameter &lt;10 µm, black smoke, sulphur dioxide and nitrogen dioxide on symptoms and PEF were estimated using logistic regression. In total, 48 (14.7%) subjects had AHR+/IgE+, 112 (34.3%) had AHR−/IgE+, 42 (12.8%) had AHR+/IgE− and 125 (38.2%) had AHR−/IgE−. In the AHR+/IgE+ group, each 10 µg·m −3 increase in air pollution was associated with a significant increase in prevalence of URS (odds ratio ranging 1.03–1.19), cough (1.03–1.08) and fall in morning PEF (1.04–1.26). In the AHR+/IgE+ group, males responded predominantly with symptoms and females with a fall in morning PEF. In conclusion, elderly individuals with both airway hyperresponsiveness and high total immunoglobulin E are especially susceptible to air pollution. Identifying susceptible subgroups might enlarge insight into the actual mechanisms by which air pollution evokes specific modes of response.
Stem cells as therapeutic vehicles for the treatment of high-grade gliomas
Authors: E. Binello, I. M. Germano
Journal: Neuro-Oncology (2011)

Stem cells have generated great interest in the past decade as potential tools for cell-based treatment of human high-grade gliomas. Thus far, 3 types of stem cells have been tested as vehicles for various therapeutic agents: embryonic, neural, and mesenchymal. The types of therapeutic approaches and/or agents examined in the context of stem cell–based delivery include cytokines, enzyme/prodrug suicide combinations, viral particles, matrix metalloproteinases, and antibodies. Each strategy has specific advantages and disadvantages. Irrespective of the source and/or type of stem cell, there are several areas of concern for their translation to the clinical setting, such as migration in the adult human brain, potential teratogenesis, immune rejection, and regulatory and ethical issues. Nonetheless, a clinical trial is under way using neural stem cell–based delivery of an enzyme/prodrug suicide combination for recurrent high-grade glioma. A proposed future direction could encompass the use of stem cells as vehicles for delivery of agents targeting glioma stem cells, which have been implicated in the resistance of high-grade glioma to treatment. Overall, stem cells are providing an unprecedented opportunity for cell-based approaches in the treatment of high-grade gliomas, which have a persistently dismal prognosis and mandate a continued search for therapeutic options.
Pneumomediastinum after a transbronchial biopsy.
Authors: M Naughton, L Irving, A McKenzie
Journal: Thorax (1991)

A pneumomediastinum occurred after a transbronchial biopsy in a woman with pulmonary fibrosis and was confirmed by computed tomography. Although pneumomediastinum has a pathogenesis similar to that of pneumothorax it has not been reported after transbronchial biopsy.
Web-Based Survey of Fertility Issues in Young Women With Breast Cancer
Authors: Ann H. Partridge, Shari Gelber, Jeffrey Peppercorn, Ebonie Sampson, Katherine Knudsen, Marc Laufer, Randi Rosenberg, Michele Przypyszny, Alison Rein, Eric P. Winer
Journal: Journal of Clinical Oncology (2004)

Young women with breast cancer often seek advice about whether treatment will affect their fertility. We sought to gain a better understanding of women's attitudes about fertility and how these concerns affect decision making.We developed a survey about fertility issues for young women with a history of early-stage breast cancer. The survey was e-mailed to all registered Young Survival Coalition survivor members (N = 1,702). E-mail reminders were used.Six hundred fifty-seven eligible respondents completed the survey. Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8 years. Ninety percent of women were white; 62% were married; 76% were college graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; II, 47%; III, 13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven percent recalled substantial concern at diagnosis about becoming infertile with treatment. In multivariate logistic regression, greater concern about infertility was associated with wish for children/more children (odds ratio [OR], 120; P < .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that infertility concerns influenced treatment decisions. Seventy-two percent of women reported discussing fertility concerns with their doctors; 51% felt their concerns were addressed adequately. Women seemed to overestimate their risk of becoming postmenopausal with treatment.Fertility after treatment is a major concern for young women with breast cancer. There is a need to communicate with and educate young patients regarding fertility issues at diagnosis and a need for future research directed at preserving fertility for young breast cancer survivors.
The end of lymphatic filariasis?
Authors: M. J Bockarie, D. H Molyneux
Journal: BMJ (2009)

Most synapses release neurotransmitters in two phases: (1) a fast synchronous phase lasting a few milliseconds; and (2) a delayed "asynchronous" phase lasting hundreds of milliseconds. Ca<sup>2+</sup> triggers fast synchronous neurotransmitter release by binding to synaptotagmin-1, synaptotagmin-2, or synaptotagmin-9, but how Ca<sup>2+</sup> triggers delayed asynchronous release has long remained enigmatic. Recent results suggested that consistent with the Ca<sup>2+</sup>-sensor function of synaptotagmin-7 in neuroendocrine exocytosis, synaptotagmin-7 also functions as a Ca<sup>2+</sup> sensor for synaptic vesicle exocytosis but operates during delayed asynchronous release. Puzzlingly, a subsequent study postulated that synaptotagmin-7 is not a Ca<sup>2+</sup> sensor for release but mediates Ca<sup>2+</sup>-dependent vesicle repriming after intense stimulation. To address these issues, we here analyzed synaptic transmission at rod bipolar neuron–AII amacrine cell synapses in acute mouse retina slices as a model system. Using paired recordings, we show that knock-out of synaptotagmin-7 selectively impairs delayed asynchronous release but not fast synchronous release. Delayed asynchronous release was blocked in wild-type synapses by intracellular addition of high concentrations of the slow Ca<sup>2+</sup>-chelator EGTA, but EGTA had no effect in synaptotagmin-7 knock-out neurons because delayed asynchronous release was already impaired. Moreover, direct measurements of vesicle repriming failed to uncover an effect of the synaptotagmin-7 knock-out on vesicle repriming. Our data demonstrate that synaptotagmin-7 is selectively essential for Ca<sup>2+</sup>-dependent delayed asynchronous release in retinal rod bipolar cell synapses, that its function can be blocked by simply introducing a slow Ca<sup>2+</sup> buffer into the cells, and that synaptotagmin-7 is not required for normal vesicle repriming. <b>SIGNIFICANCE STATEMENT</b> How Ca<sup>2+</sup> triggers delayed asynchronous release has long remained enigmatic. Synaptotagmin-7 has been implicated recently as Ca<sup>2+</sup> sensor in mediating delayed asynchronous release, or vesicle repriming, in cultured neurons. To test the precise function of synaptotagmin-7 in a physiologically important synapse <i>in situ</i>, we have used pair recordings to study the synaptic transmission between retinal rod bipolar cells and AII amacrine cells. Our data demonstrate that the knock-out of synaptotagmin-7 selectively impaired delayed asynchronous release but not synchronous release. In contrast, the readily releasable vesicles after depletion recover normally in knock-out mice. Therefore, our findings extend our knowledge of synaptotagmins as Ca<sup>2+</sup> sensors in vesicle fusion and support the idea that synapses are governed universally by different synaptotagmin Ca<sup>2+</sup> sensors mediating distinct release.
RETRACTED: Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development
Authors: Flavia Pichiorri, Sung-Suk Suh, Alberto Rocci, Luciana De Luca, Cristian Taccioli, Ramasamy Santhanam, Wenchao Zhou, Don M. Benson, Craig Hofmainster, Hansjuerg Alder, Michela Garofalo, Gianpiero Di Leva, Stefano Volinia, Huey-Jen Lin, Danilo Perrotti, Michael Kuehl, Rami I. Aqeilan, Antonio Palumbo, Carlo M. Croce
Journal: Cancer Cell (2010)
Association between human rhinovirus C and severity of acute asthma in children
Authors: J. Bizzintino, W-M. Lee, I.A. Laing, F. Vang, T. Pappas, G. Zhang, A.C. Martin, S-K. Khoo, D.W. Cox, G.C. Geelhoed, P.C. McMinn, J. Goldblatt, J.E. Gern, P.N. Le Souëf
Journal: European Respiratory Journal (2010)

A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. Children with acute asthma (n = 128; age 2–16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate. The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.
Sex Differences in the Use of Implantable Cardioverter-Defibrillators for Primary and Secondary Prevention of Sudden Cardiac Death
Authors: Lesley H. Curtis, Sana M. Al-Khatib, Alisa M. Shea, Bradley G. Hammill, Adrian F. Hernandez, Kevin A. Schulman
Journal: JAMA (2007)

Previous studies of sex differences in the use of implantable cardioverter-defibrillators (ICDs) predate recent expansions in Medicare coverage and did not provide patient follow-up over multiple years.To examine sex differences in ICD use for primary and secondary prevention of sudden cardiac death.Analysis of a 5% national sample of research-identifiable files obtained from the US Centers for Medicare & Medicaid Services for the period 1991 through 2005. Patients were those aged 65 years or older with Medicare fee-for-service coverage and diagnosed with acute myocardial infarction and either heart failure or cardiomyopathy but no prior cardiac arrest or ventricular tachycardia (ie, the primary prevention cohort [n = 65,917 men and 70,504 women]), or with cardiac arrest or ventricular tachycardia (ie, the secondary prevention cohort [n = 52,252 men and 47,411 women]), from 1999 through 2005.Receipt of ICD therapy and all-cause mortality at 1 year.In the 2005 primary prevention cohort, 32.3 per 1000 men and 8.6 per 1000 women received ICD therapy within 1 year of cohort entry. In multivariate analyses, men were more likely than women to receive ICD therapy (hazard ratio [HR], 3.15; 95% confidence interval [CI], 2.86-3.47). Among men and women alive at 180 days after cohort entry, the hazard of mortality in the subsequent year was not significantly lower among those who received ICD therapy (HR, 1.01; 95% CI, 0.82-1.23). In the 2005 secondary prevention cohort, 102.2 per 1000 men and 38.4 per 1000 women received ICD therapy. Controlling for demographic variables and comorbid conditions, men were more likely than women to receive ICD therapy (HR, 2.44; 95% CI, 2.30-2.59). Among men and women alive at 30 days after cohort entry, the hazard of mortality in the subsequent year was significantly lower among those who received ICD therapy (HR, 0.65; 95% CI, 0.60-0.71).In the Medicare population, women are significantly less likely than men to receive ICD therapy for primary or secondary prevention of sudden cardiac death.
Anorectics on Trial: A Half Century of Federal Regulation of Prescription Appetite Suppressants
Authors: Eric Colman
Journal: Annals of Internal Medicine (2005)

Beginning with the passage of the Federal Food, Drug, and Cosmetic Act in 1938 and escalating with the 1962 Kefauver-Harris amendments, increasing pressure has been placed on pharmaceutical manufacturers to demonstrate that a drug's benefits outweigh its risks. Nowhere has the question of risk versus benefit come under greater scrutiny than with anorectics. After the approval in the 1940s and 1950s of a number of amphetamine and amphetamine-like compounds for the treatment of obesity, the U.S. Food and Drug Administration struggled to define the efficacy and safety of these agents. Labeling restrictions on duration of use and warnings about abuse and addiction ultimately contributed to the reduced use of anorectics. That trend continued until the mid-1990s, when the off-label use of fenfluramine plus phentermine (fen-phen) and the approval of dexfenfluramine gave rise to widespread, long-term use of anorectics to treat obesity. The adverse effects that came to be associated with fenfluramine and dexfenfluramine, leading to their eventual withdrawal from the market, gave pause to regulators, physicians, patients, and drug companies alike. Sibutramine, the latest anorectic to enter the market, is now the focus of a landmark trial that is examining, for the first time, whether drug-induced weight loss reduces the risk for fatal and nonfatal cardiovascular disease.