tbuckley/cabot-search huggingface dataset:
Where do our reviewers come from?
Authors: T Opthof
Journal: Cardiovascular Research (2000)

In this issue we acknowledge the help of over 2,500 reviewers who produced more than 10 000 reports since we took office in June 1995. There is only limited information on the quality of such reports and on the way editors select new reviewers and thereby consolidate and expand the backbone of their journals. Although editors and not reviewers make decisions on the fate of manuscripts, it is obvious that an editor will not easily accept a paper when it has received negative reviewer's reports. On the other hand positive reports are no guarantee that a paper will be published because page limitations force editors to make priority decisions [1]. The characteristics of good reviewers have been assessed on the basis of information from the Journal of General Internal Medicine [2]. The outcome of this analysis was a little surprising in some aspects. Good reviewers were young, had received research training (J Gen Intern Med is a clinical journal), had an additional degree to a MD and that came from an institute with prestige. It also helped when they were known by the editor and when the authors were blinded to the reviewer. Time spent on the review was another positively correlated factor. The membership of an Editorial Board had no effect and there was a trend to an inverse relation between academic rank and performance. Assistant professors and fellows tended to do better than associate professors, whereas the latter did better than full professors. Surprisingly, the publication record of the reviewer was not significantly correlated with the quality of the produced reports. It has been suggested that young reviewers perform well because they spend a lot of time on a review and that older, more experienced reviewers would be better capable to put the work in perspective [3,4] … 

* Corresponding author. Tel.: +31-20-566-3265; fax: +31-20-697-5458
Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy
Authors: A. Al-Omair, L. Masucci, L. Masson-Cote, M. Campbell, E. G. Atenafu, A. Parent, D. Letourneau, E. Yu, R. Rampersaud, E. Massicotte, S. Lewis, A. Yee, I. Thibault, M. G. Fehlings, A. Sahgal
Journal: Neuro-Oncology (2013)

Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival. Eighty patients treated between October 2008 and February 2012 with postoperative SBRT were identified from our prospective database and retrospectively reviewed. The median follow-up was 8.3 months. Thirty-five patients (44%) were treated with 18–26 Gy in 1 or 2 fractions, and 45 patients (56%) with 18–40 Gy in 3–5 fractions. Twenty-one local failures (26%) were observed, and the 1-year LC and overall survival (OS) rates were 84% and 64%, respectively. The most common site of failure was within the epidural space (15/21, 71%). Multivariate proportional hazards analysis identified systemic therapy post-SBRT as the only significant predictor of OS (P = .02) and treatment with 18–26 Gy/1 or 2 fractions (P = .02) and a postoperative epidural disease grade of 0 or 1 (0, no epidural disease; 1, epidural disease that compresses dura only, P = .003) as significant predictors of LC. Subset analysis for only those patients (n = 48/80) with high-grade preoperative epidural disease (cord deformed) indicated significantly greater LC rates when surgically downgraded to 0/1 vs 2 (P = .0009). Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1–2 fractions predicted superior LC, as did postoperative epidural grade.
Second primary lung carcinoma.
Authors: R A Smith, B K Nigam, J M Thompson
Journal: Thorax (1976)

Ffity-five patients suffering from second primary lung carcinoma, 10 synchronous and 45 after resection for lung carcinoma (metachronous), have been observed from 1400 resections. The first manifestation of a second carcinoma in this series has always been the appearance of a new shadow in the follow-up radiograph. In our experience, second primary lung carcinoma is a disease affecting only heavy cigarette smokers. Heavy cigarette smokers suffering from squamous-cell carcinoma are at special risk. The results of re-operation, the significance of the time interval between the original operation and the appearance of the second primary carcinoma, and the slow growth rate of some second primaries are briefly discussed. No clear-cut methods exist for distinguishing a second primary from a metastasis from the original carcinoma.
Relationship between Plasma Exposure of 9-Nitrocamptothecin and Its 9-Aminocamptothecin Metabolite and Antitumor Response in Mice Bearing Human Colon Carcinoma Xenografts
Authors: William C. Zamboni, Laura L. Jung, Merrill J. Egorin, Deborah R. Hamburger, Erin Joseph, Ruzhi Jin, Sandra Strychor, Ramesh K. Ramanathan, Julie L. Eiseman
Journal: Clinical Cancer Research (2005)

9-Nitrocamptothecin has completed phase III studies in patients with newly diagnosed and refractory pancreatic cancer; however, the optimal 9-nitrocamptothecin treatment regimen is unclear. We used an intermittent schedule of 9-nitrocamptothecin to evaluate the relationship between plasma exposure of 9-nitrocamptothecin and its 9-aminocamptothecin metabolite and antitumor response in mice bearing human colon carcinoma xenografts. 9-Nitrocamptothecin was given orally at 0.44, 0.67, or 1.0 mg/kg/d qd x 5d x 2 weeks repeated q 4 weeks for two cycles to female C.B-17 SCID mice bearing HT29 or ELC2 human colon xenografts. Pharmacokinetic studies were done after oral administration of 0.67 mg/kg x 1. Serial samples were obtained and 9-nitrocamptothecin and 9-aminocamptothecin lactone concentrations in plasma were determined by high-performance liquid chromatography analysis with fluorescence detection. The areas under plasma concentration versus time curve (AUC) from 0 to infinity for 9-nitrocamptothecin and 9-aminocamptothecin were calculated. The antitumor activity of 9-nitrocamptothecin was dose-dependent in both colon xenografts. At all doses, 9-nitrocamptothecin treatment resulted in significant antitumor activity in both xenografts compared with vehicle-treated and control groups and achieved levels of tumor regression that met criteria (minimum %T/C < or = 40%) for antitumor activity. In mice bearing HT29 xenografts, the 9-nitrocamptothecin and 9-aminocamptothecin lactone AUCs after administration of 9-nitrocamptothecin at 0.67 mg/kg were 41.3 and 5.7 ng/mL h, respectively. The responses seen in these xenograft models occurred at systemic exposures that are tolerable in adult patients. These results suggest that the intermittent schedule of 9-nitrocamptothecin may be an active regimen in patients with colorectal carcinoma.
The effect of calcium antagonists on allergic pulmonary distress in actively sensitized rats
Authors: E. S. Korach, G. W. Carnathan, R. L. Aspinall
Journal: Allergy (1987)

The induction of allergic pulmonary distress (APD) in ovalbumin sensitive rats can be used as a model of human allergic asthma. In this model, control animals exhibit a rapid decrease in minute volume (Vm) when challenged with ovalbumin (OA) by aerosol (3 % solution). The present study compared the effects of pretreatment with calcium antagonists on the induction of APD. By the aerosol route of administration, 5 min before OA, verapamil HCl (6% solution) significantly ( P &lt; 0.05) dampened the allergic response during all 12 min monitored. At an equivalent concentration, diltiazem aHCl significantly ( P &lt; 0.05) inhibited the response during 6 of 12 min, whereas nifedipine failed to significantly ( P &gt; 0.05) alter the response to OA. Verapamil and nifedipine proved to be equally effective in a dose‐dependent manner against OA‐induced APD, however, when administered orally (‐60 min, 5, 10 or 20 mg/kg). At doses of 10 mg/kg and higher, both calcium antagonists consistently inhibited ( P &lt; 0.05) the response. Diltiazem was inactive when administered orally at a dose as high as 20 mg/kg. The present data suggest that the calcium antagonists verapamil, nifedipine and diltiazem, can attenuate APD and therefore might be clinically active agents in the treatment of allergic asthma.
The Role of Mechanical Forces in Tumor Growth and Therapy
Authors: Rakesh K. Jain, John D. Martin, Triantafyllos Stylianopoulos
Journal: Annual Review of Biomedical Engineering (2014)

Tumors generate physical forces during growth and progression. These physical forces are able to compress blood and lymphatic vessels, reducing perfusion rates and creating hypoxia. When exerted directly on cancer cells, they can increase cells' invasive and metastatic potential. Tumor vessels—while nourishing the tumor—are usually leaky and tortuous, which further decreases perfusion. Hypoperfusion and hypoxia contribute to immune evasion, promote malignant progression and metastasis, and reduce the efficacy of a number of therapies, including radiation. In parallel, vessel leakiness together with vessel compression causes a uniformly elevated interstitial fluid pressure that hinders delivery of blood-borne therapeutic agents, lowering the efficacy of chemo- and nanotherapies. In addition, shear stresses exerted by flowing blood and interstitial fluid modulate the behavior of cancer and a variety of host cells. Taming these physical forces can improve therapeutic outcomes in many cancers.
The clinical presentation of paediatric narcolepsy in one Canadian sleep centre
Authors: Andrea Riekstins, Glenda Bendiak, Shelly Weiss, Indra Narang
Journal: European Respiratory Journal (2012)

Narcolepsy is primarily characterized by an overwhelming feeling of sleepiness with or without cataplexy. More recently, there has been a dramatic increase in newly diagnosed childhood narcolepsy and it is hypothesized that H1N1 may play a role in these new cases. The objective of this study is to review the demographics and presenting symptoms of children with narcolepsy in Toronto.

Methods: At the Hospital for Sick Children, Toronto, we reviewed medical records and polysomnograms of patients with narcolepsy who presented to the sleep disorders clinic. All patients were referred with a history of excessive daytime sleepiness.

Results:

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Conclusion: All patients had excessive daytime sleepiness. Interestingly over half of these young patients had cataplexy on presentation. H1N1 vaccination was not given to the majority of these patients. More research is needed to understand the recent increase in the prevalence of childhood narcolepsy with cataplexy.
Chemotactic activity of Helicobacter pylori sonicate for human polymorphonuclear leucocytes and monocytes.
Authors: H Nielsen, L P Andersen
Journal: Gut (1992)

The immunopathology of Helicobacter pylori associated active chronic gastritis, which is characterised by predominance of polymorphonuclear leucocyte infiltration, is largely unknown. To evaluate the role of bacterial components as inflammatory mediators ultracentrifuged sonicated preparations were made of clinical isolates of Helicobacter pylori. The crude sonicates were shown to exhibit chemotactic activity for human polymorphonuclear leucocytes and blood monocytes in a concentration dependent fashion. The potency was comparable with previously described bacterial derived cytotaxins. The cytotaxin(s) was non-dialysable and completely destroyed by proteinase. Heat treatment did not decrease the chemotactic activity, but in sonicate subjected to 100 degrees C for 15 minutes all activity disappeared after dialysis suggesting the breakdown of a larger protein to small fragments that are still biological active. By ammonium sulphate precipitation at increasing concentrations the cytotaxin(s) was selectively found in 10% ammonium sulphate saturation, and by further molecular gel separation the chemotactic activity was found in the molecular size range from 25 to 35 kDa. The demonstration of a polymorphonuclear leucocyte and monocyte cytotaxin from Helicobacter pylori sonicate may help in understanding the mucosal immune response in gastric inflammatory diseases.
Apparent pulmonary mycetoma following invasive aspergillosis in neutropenic patients.
Authors: C C Kibbler, S R Milkins, A Bhamra, M A Spiteri, P Noone, H G Prentice
Journal: Thorax (1988)

After the death from massive haemoptysis of two neutropenic patients who had developed apparent pulmonary mycetomas, two subsequent patients underwent successful resection of similar lesions. Histological examination of these lesions confirmed that these so called mycetomas were masses of devitalized lung tissue infiltrated with fungus. The term mycotic lung sequestrum is therefore proposed to distinguish this condition from a fungus ball arising in a previously formed cavity. A review of 34 similar cases reported previously showed that haemoptysis occurred in about half of the cases and was fatal in just over half of these. Medical treatment appears to have little impact on survival and early consideration of surgical intervention is important.
Three Distinct Types of Ca <sup>2+</sup> Waves in Langendorff-Perfused Rat Heart Revealed by Real-Time Confocal Microscopy
Authors: Tomoyuki Kaneko, Hideo Tanaka, Masahito Oyamada, Satoshi Kawata, Tetsuro Takamatsu
Journal: Circulation Research (2000)

Abstract —Although Ca 2+ waves in cardiac myocytes are regarded as arrhythmogenic substrates, their properties in the heart in situ are poorly understood. On the hypothesis that Ca 2+ waves in the heart behave diversely and some of them influence the cardiac function, we analyzed their incidence, propagation velocity, and intercellular propagation at the subepicardial myocardium of fluo 3–loaded rat whole hearts using real-time laser scanning confocal microscopy. We classified Ca 2+ waves into 3 types. In intact regions showing homogeneous Ca 2+ transients under sinus rhythm (2 mmol/L [Ca 2+ ] o ), Ca 2+ waves did not occur. Under quiescence, the waves occurred sporadically (3.8 waves · min −1 · cell −1 ), with a velocity of 84 μm/s, a decline half-time (t 1/2 ) of 0.16 seconds, and rare intercellular propagation (propagation ratio &lt;0.06) (sporadic wave). In contrast, in presumably Ca 2+ -overloaded regions showing higher fluorescent intensity (113% versus the intact regions), Ca 2+ waves occurred at 28 waves · min −1 · cell −1 under quiescence with a higher velocity (116 μm/s), longer decline time (t 1/2 =0.41 second), and occasional intercellular propagation (propagation ratio=0.23) (Ca 2+ -overloaded wave). In regions with much higher fluorescent intensity (124% versus the intact region), Ca 2+ waves occurred with a high incidence (133 waves · min −1 · cell −1 ) and little intercellular propagation (agonal wave). We conclude that the spatiotemporal properties of Ca 2+ waves in the heart are diverse and modulated by the Ca 2+ -loading state. The sporadic waves would not affect cardiac function, but prevalent Ca 2+ -overloaded and agonal waves may induce contractile failure and arrhythmias.
Adjuvant Chemotherapy and Survival in Older Women With Hormone Receptor–Negative Breast Cancer: Assessing Outcome in a Population-Based, Observational Cohort
Authors: Elena B. Elkin, Arti Hurria, Nandita Mitra, Deborah Schrag, Katherine S. Panageas
Journal: Journal of Clinical Oncology (2006)

For older breast cancer patients, there is limited evidence of the efficacy of adjuvant chemotherapy from randomized clinical trials. Our goal was to assess the relationship between adjuvant chemotherapy use and survival in a large, population-based cohort of older women with hormone receptor (HR) -negative breast cancer.We identified women age 66 and older diagnosed with HR-negative, nonmetastatic breast cancer from 1992 to 1999 in the Surveillance, Epidemiology and End Results (SEER) cancer registries. Chemotherapy use was identified in Medicare claims linked to SEER records. Clinical and sociodemographic predictors of chemotherapy use were identified using logistic regression. The effect of chemotherapy on survival was evaluated using propensity score methods and multivariable proportional hazards regression.A total of 1,711 (34%) of 5,081 women with HR-negative breast cancer received chemotherapy within 6 months of cancer diagnosis. Chemotherapy use decreased with increasing age and comorbidity, and increased with year of diagnosis, tumor size, number of positive lymph nodes, and higher tumor grade. Adjuvant chemotherapy was associated with a mortality reduction of approximately 15% whether analyzed using propensity scores or standard multivariable methods. The greatest overall survival benefit was observed in patients with node-positive disease and in the node-negative patients most likely to receive chemotherapy.This analysis suggests a survival benefit from adjuvant chemotherapy in older women with HR-negative breast cancer. The benefit of chemotherapy is most pronounced in the patients most likely to be selected for treatment, including those with involved lymph nodes or other high-risk disease characteristics.
Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons
Authors: Perrine Hoet, Mary Louise M Graf, Mohammed Bourdi, Lance R Pohl, Paul H Duray, Weiqiao Chen, Raimund M Peter, Sidney D Nelson, Nicolas Verlinden, Dominique Lison
Journal: The Lancet (1997)

Background Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. Methods For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). Findings The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. Interpretation Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.
Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis.
Authors: I J Benjamin, J E Jalil, L B Tan, K Cho, K T Weber, W A Clark
Journal: Circulation Research (1989)

Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with [3H]thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss.
Autophagy Is Activated by TGF-β and Potentiates TGF-β–Mediated Growth Inhibition in Human Hepatocellular Carcinoma Cells
Authors: Kunihiko Kiyono, Hiroshi I. Suzuki, Hironori Matsuyama, Yasuyuki Morishita, Akiyoshi Komuro, Mitsunobu R. Kano, Koichi Sugimoto, Kohei Miyazono
Journal: Cancer Research (2009)

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell growth, differentiation, and apoptosis of various types of cells. Autophagy is emerging as a critical response of normal and cancer cells to environmental changes, but the relationship between TGF-beta signaling and autophagy has been poorly understood. Here, we showed that TGF-beta activates autophagy in human hepatocellular carcinoma cell lines. TGF-beta induced accumulation of autophagosomes and conversion of microtubule-associated protein 1 light chain 3 and enhanced the degradation rate of long-lived proteins. TGF-beta increased the mRNA expression levels of BECLIN1, ATG5, ATG7, and death-associated protein kinase (DAPK). Knockdown of Smad2/3, Smad4, or DAPK, or inhibition of c-Jun NH(2)-terminal kinase, attenuated TGF-beta-induced autophagy, indicating the involvement of both Smad and non-Smad pathway(s). TGF-beta activated autophagy earlier than execution of apoptosis (6-12 versus 48 h), and reduction of autophagy genes by small interfering RNA attenuated TGF-beta-mediated growth inhibition and induction of proapoptotic genes Bim and Bmf, suggesting the contribution of autophagy pathway to the growth-inhibitory effect of TGF-beta. Additionally, TGF-beta also induced autophagy in some mammary carcinoma cells, including MDA-MB-231 cells. These findings show that TGF-beta signaling pathway activates autophagy in certain human cancer cells and that induction of autophagy is a novel aspect of biological functions of TGF-beta.
Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma
Authors: G. Lurje, H. Husain, D.G. Power, D. Yang, S. Groshen, A. Pohl, W. Zhang, Y. Ning, P.C. Manegold, A. El-Khoueiry, S. Iqbal, L.H. Tang, M.A. Shah, H.-J. Lenz
Journal: Annals of Oncology (2009)