tbuckley/cabot-search huggingface dataset:
Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance
Authors: George N. Naumov, Monique B. Nilsson, Tina Cascone, Alexandra Briggs, Oddbjorn Straume, Lars A. Akslen, Eugene Lifshits, Lauren Averett Byers, Li Xu, Hua-kang Wu, Pasi Jänne, Susumu Kobayashi, Balazs Halmos, Daniel Tenen, Xi M. Tang, Jeffrey Engelman, Beow Yeap, Judah Folkman, Bruce E. Johnson, John V. Heymach
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib benefit some non–small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance) and those who initially respond eventually progress (acquired resistance). EGFR TKI resistance is not completely understood and has been associated with certain EGFR and K-RAS mutations and MET amplification. Experimental Design: We hypothesized that dual inhibition of the vascular endothelial growth factor (VEGF) and EGFR pathways may overcome primary and acquired resistance. We investigated the VEGF receptor/EGFR TKI vandetanib, and the combination of bevacizumab and erlotinib in vivo using xenograft models of EGFR TKI sensitivity, primary resistance, and three models of acquired resistance, including models with mutated K-RAS and secondary EGFR T790M mutation. Results: Vandetanib, gefitinib, and erlotinib had similar profiles of in vitro activity and caused sustained tumor regressions in vivo in the sensitive HCC827 model. In all four resistant models, vandetanib and bevacizumab/erlotinib were significantly more effective than erlotinib or gefitinib alone. Erlotinib resistance was associated with a rise in both host and tumor-derived VEGF but not EGFR secondary mutations in the KRAS mutant-bearing A549 xenografts. Dual inhibition reduced tumor endothelial proliferation compared with VEGF or EGFR blockade alone, suggesting that the enhanced activity of dual inhibition is due at least in part to antiendothelial effects. Conclusion: These studies suggest that erlotinib resistance may be associated with a rise in both tumor cell and host stromal VEGF and that combined blockade of the VEGFR and EGFR pathways can abrogate primary or acquired resistance to EGFR TKIs. This approach merits further evaluation in NSCLC patients.
Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study
Authors: F. Islami, A. Pourshams, D. Nasrollahzadeh, F. Kamangar, S. Fahimi, R. Shakeri, B. Abedi-Ardekani, S. Merat, H. Vahedi, S. Semnani, C. C Abnet, P. Brennan, H. Moller, F. Saidi, S. M Dawsey, R. Malekzadeh, P. Boffetta
Journal: BMJ (2009)

<h3>Abstract</h3> While traditional studies claim that visuospatial attention stays fixed at one location at a time, recent research has rather shown that attention rhythmically fluctuates between different locations at rates of prominent brain rhythms. However, little is known about the temporal dynamics of this fluctuation and, particularly, whether it changes over time. Thus, we addressed this question by investigating how visuospatial attention behaves over space and time. We recorded electroencephalographic activity of twenty-seven human participants while they performed a visuospatial cueing task, where attention was covertly oriented to the left or right visual field. In order to decode the spatial locus of attention from neural activity, we trained and tested a classifier on every timepoint of the orienting period, from the attentional cue to stimulus onset. This resulted in one temporal generalization matrix per participant, which was time-frequency decomposed to identify the sampling rhythm. Finally, a searchlight analysis was conducted to reveal the brain regions responsible for attention allocation. Our results show a dynamic evolution of the attentional spotlight, distinguishing between two states. In an early time window, attention explored both cued and uncued hemifield rhythmically at ~10 Hz. In a later time window attention focused on the cued hemifield. Classification was driven by occipital sources, while frontal regions exclusively became involved just before the spotlight settled onto the cued location. Together, our results define attentional sampling as a quasi-rhythmic dynamic process characterized by an initial rhythmic exploration-exploitation state, which is followed by a stable exploitation state.
Doctor who botched sterilisation has to pay cost of raising child
Authors: C. Zinn
Journal: BMJ (2003)

After a recent High Court decision it seems that doctors whose negligence results in a patient giving birth after a failed sterilisation operation might have to pay the costs of bringing up the children until they are aged 18.

In a 4-3 decision Australia's highest court held that an obstetrician and gynaecologist who performed an unsuccessful tubal ligation in 1992 must pay $A105 000 (£43 000; $68 000; €60 000) towards the costs of raising the woman's son.

Kerry and Craig Melchior sued after she gave birth to their third child, a boy called Jordan, five years after the laparoscopic sterilisation performed by Dr …
Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system?
Authors: Bellinda A. Bladergroen, Chris J. L. M. Meijer, Rosita L. ten Berge, C. Erik Hack, Jettie J. F. Muris, Danny F. Dukers, Andreas Chott, Yoshiaki Kazama, Joost J. Oudejans, Oskar van Berkum, J. Alain Kummer
Journal: Blood (2002)
Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials
Authors: A. G Renehan
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer. <b>Design:</b> Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up. <b>Main outcome measures:</b> All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes). <b>Results:</b> Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P&lt;0.001) and an increased detection rate for isolated local recurrences (risk ratio 1.61, 1.12 to 2.32, P=0.011). <b>Conclusions:</b> Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial. <h3>What is already known on this topic</h3> There is a lack of direct evidence that intensive follow up after initial curative treatment for colorectal cancer leads to increased survival Guidelines are inconclusive and clinical practice varies widely <h3>What this study adds</h3> The cumulative analysis of available data supports the view that intensive follow up after curative resection for colorectal cancer improves survival If computed tomography and frequent measurements of serum carcinoembryonic antigen are used during follow up mortality related to cancer is reduced by 9-13% This survival benefit is partly attributable to the earlier detection of all recurrences, particularly the increased detection of isolated recurrent disease
Abstract 2293: A fast and simple method for whole-genome bisulfite library preparation from ultra-low DNA inputs
Authors: Karolyn Giang, TzuHung Chung, Xueguang Sun, Marc E. Van Eden, Xi Yu Jia
Journal: Cancer Research (2014)

Abstract The distribution of 5-methylcytosine (5-mC) in DNA within the eukaryotic genome is known to greatly affect gene regulation and is currently a major topic of research. Studies on DNA methylation have been aided by advancements in bisulfite conversion and Next-Gen sequencing technologies which can provide single-base resolution of 5-mC across the entire genome. Many whole-genome bisulfite sequencing (WGBS) library preparation protocols designed for analysis of 5-mC distribution employ bisulfite to chemically convert unmethylated cytosine bases into uracil following the library preparation step. While these protocols produce reliable results, degradation of DNA is always an inherent issue when dealing with bisulfite conversion, and a large proportion of the adapterized library is often fragmented and can no longer be amplified. This requires high levels of DNA to serve as the input material. However, by rearranging the order of library preparation and bisulfite conversion, we developed a streamlined protocol that necessitates less input material for accurate whole-genome methylation analysis at single-base resolution. This unique workflow accommodates picogram quantities of starting material, making it ideal for analysis of precious samples that are of limited availability (e.g., FFPE). Comparison of sequencing data generated using this new library preparation method and data generated with established Reduced Representation Bisulfite Sequencing demonstrated a correlation of 0.95 in CpG sites with &amp;gt; 10X coverage in human DNA. Also, with only slight modification, this protocol is versatile enough to be used in the preparation of libraries for ChIP-Seq and RNA-Seq analyses. Citation Format: Karolyn Giang, TzuHung Chung, Xueguang Sun, Marc E. Van Eden, Xi Yu Jia. A fast and simple method for whole-genome bisulfite library preparation from ultra-low DNA inputs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2293. doi:10.1158/1538-7445.AM2014-2293
Injury data of major international field hockey tournaments
Authors: Till-Martin Theilen, Wiebke Mueller-Eising, Peter Wefers Bettink, Udo Rolle
Journal: British Journal of Sports Medicine (2015)

Detailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.FIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.The average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.Field hockey has a low incidence of acute injuries during competition.
On the Cause of Ventricular Asystole during Vagal Stimulation
Authors: MARIO VASSALLE, DONALD L. CARESS, ALVIN J. SLOVIN, JACKSON H. STUCKEY
Journal: Circulation Research (1967)

In anesthetized dogs the vagus nerve was stimulated for 2 min; during the first minute the ventricles were driven at a rate higher than the control sinus rate; after discontinuation of the drive, the duration of asystole was prolonged. When the ventricles were driven at a rate lower than the sinus rate during vagal stimulation the subsequent asystole was shortened. Slowing sinus activity by graded vagal stimulation before maximal vagal stimulation led to a shorter asystole. Driving the ventricles at a rate higher than the sinus node rate before vagal stimulation resulted in longer asystole. In animals with chronic atrioventricular block, "overdriving" the ventricles resulted in subsequent temporary inhibition of ventricular pacemakers. In dogs with atrioventricular block, coronary sinus plasma potassium increased during the period of ventricular overdriving, and the magnitude of the rise was a function of the driving rate. These results support the concept that ventricular asystole results from the suppressive action of the fast rate imposed by the sinus node upon the slowly discharging ventricular pacemakers. Suppression of sinus node activity by the vagus reveals the rate-dependent inhibition of ventricular pacemakers. The mechanism of inhibition may be related to changes in ionic concentration gradients.
Vascular Adrenoceptors: An Update
Authors: Serafim Guimarães, Daniel Moura
Journal: Pharmacological Reviews (2001)

The total and regional peripheral resistance and capacitance of the vascular system is regulated by the sympathetic nervous system, which influences the vasculature mainly through changes in the release of catecholamines from both the sympathetic nerve terminals and the adrenal medulla. The knowledge of the targets for noradrenaline and adrenaline, the main endogenous catecholamines mediating that influence, has recently been greatly expanded. From two types of adrenoceptors (alpha and beta), we have now nine subtypes (alpha1A, alpha1B, alpha1D, alpha2A/D, alpha2B, alpha2A/D, beta1, beta2, and beta3) and two other candidates (alpha1L and beta4), which may be conformational states of alpha1A and beta1-adrenoceptors, respectively. The vascular endothelium is now known to be more than a pure anatomical entity, which smoothly contacts the blood and forms a passive barrier against plasma lipids. Instead, the endothelium is an important organ possessing at least five different adrenoceptor subtypes (alpha2A/D, alpha2C, beta1, beta2, and beta3), which either directly or through the release of nitric oxide actively participate in the regulation of the vascular tone. The availability of transgenic models has resulted in a stepwise progression toward the identification of the role of each adrenoceptor subtype in the regulation of blood pressure and fine-tuning of blood supply to the different organs: alpha2A/D-adrenoceptors are involved in the central control of blood pressure; alpha1-(primarily) and alpha2B-adrenoceptors (secondarily) contribute to the peripheral regulation of vascular tone; and alpha2A/D- and alpha2C-adrenoceptors modulate transmitter release. The increased knowledge on the involvement of vascular adrenoceptors in many diseases like Raynaud's, scleroderma, several neurological degenerative diseases (familial amyloidotic polyneuropathy, Parkinson disease, multiple-system atrophy), some kinds of hypertension, etc., will contribute to new and better therapeutic approaches.
Contribution of endothelial cells to calcium-dependent fluorescence transients in rabbit hearts loaded with indo 1.
Authors: B H Lorell, C S Apstein, M J Cunningham, F J Schoen, E O Weinberg, G A Peeters, W H Barry
Journal: Circulation Research (1990)

In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluorescence of the left ventricle during continuous excitation at 360 nm. In cells containing indo 1, an increase in [Ca2+]i is associated with an increase in fluorescence intensity at 400 nm, a decrease in intensity at 500 nm, and an increase in the 400:500 nm ratio. Beat-to-beat fluorescence transients were recorded from the surface of the heart coincident with contraction, indicating that a component of the fluorescence signals is derived from beating myocytes. To evaluate the potential contribution of endothelial cells, we compared the response to increases in [Ca2+]o or bradykinin (10(-5) M). In response to an increase of the [Ca2+] in the perfusate from 0.6 to 3.0 mM, left ventricular developed pressure and +dP/dt increased with a simultaneous increase in the [Ca2+]i-sensitive 400:500 nm ratio. Perfusion with the endothelial cell agonist bradykinin caused no change in left ventricular isovolumic peak systolic pressure or left ventricular dP/dt, whereas bradykinin evoked an immediate elevation in both the diastolic and systolic levels of the [Ca2+]i-sensitive 400:500 nm ratio. In additional experiments with indo 1-loaded isolated beating myocytes, superfusion with bradykinin had no effect on either the fluorescence [Ca2+]i transients or contractility. In contrast, superfusion of indo 1-loaded cultured endothelial cells with bradykinin caused the elevation of [Ca2+]i within seconds. Fluorescence microscopy of unstained frozen tissue sections from indo 1-loaded hearts also suggested the presence of more intense microvascular endothelial cell indo 1 fluorescence relative to that observed in myocytes. These experiments provide evidence that a component of [Ca2+]i-sensitive fluorescence of whole hearts loaded with indo 1 is contributed by nonmyocyte sources, including endothelial cells. These results also raise the caution that the abrupt rise of [Ca2+]i that has been observed during the initial phase of ischemia in whole hearts loaded with indo 1 may be partly derived from endothelial cells rather than myocytes.
Role of Hyperphosphatemia and 1,25-Dihydroxyvitamin D in Vascular Calcification and Mortality in Fibroblastic Growth Factor 23 Null Mice
Authors: Jason R. Stubbs, Shiguang Liu, Wen Tang, Jianping Zhou, Yong Wang, Xiaomei Yao, L. Darryl Quarles
Journal: Journal of the American Society of Nephrology (2007)

Fibroblastic growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1alpha-hydroxylase activity. Ablation of FGF23 results in elevated serum phosphate, calcium, and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D] levels; vascular calcifications; and early death. For determination of the independent roles of hyperphosphatemia and excess vitamin D activity on the observed phenotypic abnormalities, FGF23 null mice were fed a phosphate- or vitamin D-deficient diet. The phosphate-deficient diet corrected the hyperphosphatemia, prevented vascular calcifications, and rescued the lethal phenotype in FGF23 null mice, despite persistent elevations of serum 1,25(OH)(2)D and calcium levels. This suggests that hyperphosphatemia, rather than excessive vitamin D activity, is the major stimulus for vascular calcifications and contributes to the increased mortality in the FGF23-null mouse model. In contrast, the vitamin D-deficient diet failed to correct either the hyperphosphatemia or the vascular calcifications in FGF23 null mice, indicating that FGF23 independently regulates renal phosphate excretion and that elevations in 1,25(OH)(2)D and calcium are not sufficient to induce vascular calcifications in the absence of hyperphosphatemia. The vitamin D-deficient diet also improved survival in FGF23 null mice in association with normalization of 1,25(OH)(2)D and calcium levels and despite persistent hyperphosphatemia and vascular calcifications, indicating that excessive vitamin D activity can also have adverse effects in the presence of hyperphosphatemia and absence of FGF23. Understanding the independent and context-dependent interactions between hyperphosphatemia and excessive vitamin D activity, as well as vascular calcifications and mortality in FGF23 null mice, may ultimately provide important insights into the management of clinical disorders of hyperphosphatemia and excess vitamin D activity.
Effect of d-Tubocurarine Chloride on Sensation in Man
Authors: J. H. Kellgren, A. J. McGowan, D. R. Wood
Journal: BMJ (1946)

A case of primary agranulocytosis in a man aged 30 is described, together with a method of treatment by continuous intramuscular drip pentose nucleotide.That recovery was probably spontaneous is discussed in the light of possible treatments.Our thanks are due to Dr.
Studies on the Persistence of Methotrexate, Cytosine Arabinoside, and Leucovorin in Serum of Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Borsa, J., Whitmore, G. F., Valeriote, F. A., Collins, D., Bruce, W. R.
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Studies on the Persistence of Methotrexate, Cytosine Arabinoside, and Leucovorin in Serum of Mice Get access J. Borsa, J. Borsa Ontario Cancer Institute and Department of Medical Biophysics, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar G. F. Whitmore, G. F. Whitmore Ontario Cancer Institute and Department of Medical Biophysics, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar F. A. Valeriote, F. A. Valeriote Ontario Cancer Institute and Department of Medical Biophysics, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Collins, D. Collins Ontario Cancer Institute and Department of Medical Biophysics, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar W. R. Bruce W. R. Bruce Ontario Cancer Institute and Department of Medical Biophysics, Toronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 42, Issue 2, February 1969, Pages 235–242, https://doi.org/10.1093/jnci/42.2.235 Published: 01 February 1969 Article history Received: 08 August 1968 Accepted: 06 November 1968 Published: 01 February 1969
COMPARISON OF CONVENTIONAL AND HIGH-SENSITIVITY TROPONIN IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH CHEST PAIN: A COLLABORATIVE META-ANALYSIS
Authors: Michael Lipinski, Nevin Baker, Ricardo Escarcega Alarcon, Rebecca Torguson, Stephen Epstein, Sally Aldous, Michael Christ, Paul Collinson, Johannes Mair, Kenji Inoue, Ulrich Lotze, Mustapha Sebbane, Jean-Paul Cristol, Yonathan Freund, Camille Chenevier-Gobeaux, Christophe Meune, Kai Eggers, Radoslaw Pracon, Donald Schreiber, Alan Wu, Jordi Ordoñez-Llanos, Allan Jaffe, Raphael Twerenbold, Christian Mueller, Ron Waksman
Journal: Journal of the American College of Cardiology (2014)