tbuckley/cabot-search huggingface dataset:
Comment re: A Comparison of DNA Copy Number Profiling Platforms
Authors: Joel Greshock, Barbara L. Weber, Bin Feng, Elena Ivanova, Ilana Perna, Alexei Protopopov, Cristina Nogueira, Lynda Chin, Katherine Nathanson
Journal: Cancer Research (2008)

In Response: The letter from Coe and colleagues acknowledges the values of our systematic approach in comparing DNA copy number profiling platforms but disagrees with how resolution and coverage were defined in the study.

We agree with Coe and colleagues that no individual aspect of platform
<i>JAMA Neurology</i>Peer Reviewers in 2013
Authors: Roger N. Rosenberg
Journal: JAMA Neurology (2014)

B Laura D. Baker Brenda Banwell Robert C. Barber Roger A. Barker Richard J. Barohn Randall J. Bateman James Battiste Carl W. Bazil* Rodney D. Bell William L. Bell Timothy Benke David A. Bennett* Tammie L. S. Benzinger Daniela Berg Gregory K. Bergey Ira H. Bernstein Kevin M. Biglan Jose Biller Laurence A. Bindoff Thomas D. Bird Deborah Blacker Craig Blackstone Thomas P. Bleck Kaj Blennow Heidi K. Blume Bradley F. Boeve Erik Boot Xandra O. Breakefield John C. S. Breitner Allan H. Bretag Alexis Brice AdamM. Brickman Mark B. Bromberg Randy L. Buckner Mark P. Burgoon Jeffrey M. Burns Ian J. Butler
Induction Chemotherapy Followed by Chemoradiotherapy Compared With Chemoradiotherapy Alone for Regionally Advanced Unresectable Stage III Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B
Authors: Everett E. Vokes, James E. Herndon, Michael J. Kelley, M. Giulia Cicchetti, Nithya Ramnath, Harvey Neill, James N. Atkins, Dorothy M. Watson, Wallace Akerley, Mark R. Green
Journal: Journal of Clinical Oncology (2007)

Purpose Standard therapy for unresectable stage III non–small-cell lung cancer includes concomitant chemoradiotherapy. In Cancer and Leukemia Group B 39801, we evaluated whether induction chemotherapy before concurrent chemoradiotherapy would result in improved survival. Patients and Methods Between July 1998 and May 2002, 366 patients were randomly assigned to arm A, which involved immediate concurrent chemoradiotherapy with carboplatin area under the concentration-time curve (AUC) of 2 and paclitaxel 50 mg/m 2 given weekly during 66 Gy of chest radiotherapy, or arm B, which involved two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m 2 administered every 21 days followed by identical chemoradiotherapy. The accrual goal was 360 patients. Results Thirty-four percent of patients were female, 66% were male, and the median age was 63 years. Grade 3 or 4 toxicities during induction chemotherapy on arm B consisted mainly of neutropenia (18% and 20%, respectively). During concurrent chemoradiotherapy, there was no difference in severity of in-field toxicities of esophagitis (grade 3 and 4 were, respectively, 30% and 2% for arm A v 28% and 8% for arm B) and dyspnea (grade 3 and 4 were, respectively, 11% and 3% for arm A v 15% and 4% for arm B). Survival differences were not statistically significant (P = .3), with a median survival on arm A of 12 months (95% CI, 10 to 16 months) versus 14 months (95% CI, 11 to 16 months) on arm B and a 2-year survival of 29% (95% CI, 22% to 35%) and 31% (95% CI, 25% to 38%). Age, weight loss before therapy, and performance status were statistically significant predictive factors. Conclusion The addition of induction chemotherapy to concurrent chemoradiotherapy added toxicity and provided no survival benefit over concurrent chemoradiotherapy alone. The median survival achieved in each of the treatment groups is low, and the routine use of weekly carboplatin and paclitaxel with simultaneous radiotherapy should be re-examined.
Workers' Compensation in the United States: High Costs, Low Benefits
Authors: L. I. Boden
Journal: Annual Review of Public Health (1995)

Studies suggest that income replacement is low for many workers with serious occupational injuries and illnesses. This review discusses three areas that hold promise for raising benefits to workers while reducing workers' compensation costs to employers: improving safety, containing medical costs, and reducing litigation. In theory, workers' compensation increases the costs to employers of injuries and so provides incentives to improve safety. Yet, taken as a whole, research does not provide convincing evidence that workers' compensation reduces injury rates. Moreover, unlike safety and health regulation, workers' compensation focuses the attention of employers on individual workers. High costs may lead employers to discourage claims and litigate when claims are filed. Controlling medical costs can reduce workers' compensation costs. Most studies, however, have focused on costs and have not addressed the effectiveness of medical care or patient satisfaction. Research also has shown that workers' compensation systems can reduce the need for litigation. Without litigation, benefits can be delivered more quickly and at lower costs.
Authors' response
Authors: A. Vitarelli
Journal: Thorax (2011)

I appreciate the interest of Dr Ahmad et al in the article by Jimenez et al 1 and the accompanying editorial2 in which it has been pointed out that the use of echocardiography, laboratory findings and venous ultrasonography should be encouraged in patients with suspected high-risk pulmonary embolism (PE), and management decisions should be taken on all collected data on a case-by-case basis. Due to the high hospital mortality in patients with PE, it is important to select those at the highest risk, who cannot be treated in an outpatient …
Drug Efficacy at G Protein–Coupled Receptors
Authors: Terry Kenakin
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Efficacy has been defined in receptor pharmacology as a proportionality factor denoting the amount of physiological response a given ligand imparts to a biological system for a given amount of receptor occupancy. While first defined in terms of response, the concept can be expanded to a wide variety of G protein–coupled receptor (GPCR) behaviors, which includes pleiotropic interaction with multiple G proteins, internalization, oligomerization, desensitization, and interaction with membrane auxilliary proteins. Thus, there can be numerous types of efficacy, and different ligands can have a range of efficacies for different receptor behaviors. This review discusses the use of the efficacy concept in GPCR models based on the thermodynamic linkage theory and also in terms of the protein ensemble theory, in which macroaffinity of ligands for an ensemble of receptor microstates produces a new ligand-bound ensemble. The pharmacological characteristics of the ligand emerge from the intersection of the ligand-bound ensemble with the various ensembles defining pharmacological receptor behaviors. Receptor behaviors discussed are activation of G proteins; ability to be phosphorylated, desensitized, and internalized; formation of dimers and oligomers; and the interaction with auxiliary membrane and cytosolic proteins. The concepts of ligand-specific receptor conformation and conditional efficacy are also discussed in the context of ligand control of physiological response.
Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial
Authors: Sanne M Dorhout Mees, Ale Algra, W Peter Vandertop, Fop van Kooten, Hans AJM Kuijsten, Jelis Boiten, Robert J van Oostenbrugge, Rustam Al-Shahi Salman, Pablo M Lavados, Gabriel JE Rinkel, Walter M van den Bergh
Journal: The Lancet (2012)
Wnt/Ca2+/NFAT Signaling Maintains Survival of Ph+ Leukemia Cells upon Inhibition of Bcr-Abl
Authors: Mark A. Gregory, Tzu L. Phang, Paolo Neviani, Francesca Alvarez-Calderon, Christopher A. Eide, Thomas O'Hare, Vadym Zaberezhnyy, Richard T. Williams, Brian J. Druker, Danilo Perrotti, James DeGregori
Journal: Cancer Cell (2010)
The novel chemokine receptor CXCR7 regulates trans-endothelial migration of cancer cells
Authors: Brian A Zabel, Susanna Lewén, Robert D Berahovich, Juan C Jaén, Thomas J Schall
Journal: Molecular Cancer (2011)

Migration of metastatic tumor cells from the bloodstream into lymph nodes is thought to be facilitated by expression of the chemokine receptors CCR7, CXCR4 and, for B cell-derived tumors, CXCR5. Expression of their respective chemokine ligands (CCL19, CCL21, CXCL12 and CXCL13) by endothelial cells inside the lymph nodes facilitates the trans-endothelial migration (TEM) of these cells through high endothelial venules into the lymph node parenchyma. It is known that CXCR7, a second CXCL12 receptor, regulates TEM of CXCR4+CXCR7+ tumor cells towards a CXCL12 source. In this study, we set out to assess the potential stimulation by CXCL12 of tumor cell TEM towards other chemokines and whether CXCR7 might be able to regulate such effects.The human Burkitt's lymphoma cell line NC-37, which expresses CXCR4, CXCR5, CXCR7 and CCR7, was selected as a model system. TEM of these cells through a human HUVEC endothelial cell monolayer was used as the main model system for these studies. Regulation of their TEM behavior by various concentrations of the various cognate chemokines for the above-mentioned receptors, placed in either the source or target wells of modified Boyden chamber migration plates, was assessed by quantifying the number of cells migrated under each experimental condition.Exposure of CXCR4⁺CXCR7⁺ cancer cells to CXCL12 greatly potentiated their TEM towards the chemokines CCL19 and CXCL13. This CXCL12-potentiated TEM was inhibited by the second CXCR7 chemokine ligand, CXCL11, as well as CXCR7-specific small molecule antagonists and antibodies. In contrast, the CXCR4 antagonist AMD3100 was less effective at inhibiting CXCL12-potentiated TEM. Thus, CXCR7 antagonists may be effective therapeutic agents for blocking CXCL12-mediated migration of CXCR4⁺CXCR7⁺ tumor cells into lymph nodes, regardless of whether the cancer cells follow a CXCL12 gradient or whether serum CXCL12 stimulates their migration towards CCR7 and CXCR5 chemokines in the lymph nodes.
Membrane Potential and Muscle Function
Authors: W W Hofmann
Journal: Annual Review of Medicine (1969)

The relationship between the  of a whole muscle and the elec­ trical polarization of its individual fiber membranes is not a simple or direct one. To be sure, the process known as excitation-contraction coupling requires at least a minimum of fairly well-defined properties and events at the fiber surfaces, but both the resting voltages across the membranes and the transient changes imposed on them by the action of transmitter sub­ stances are, themselves, dependent upon the metabolic environment and are affected by the immediately preceding history of the junction. Further, the contractile machinery can be activated without any change in the membrane potential (1-3), or even if the membrane has been removed (4, 5), and both transmembrane voltage and action potentials in a fatigued (6, 7) or poisoned (8,9) muscle may remain normal while the contractions fail entirely. In the normal muscle in vivo, however, the fundamental relationship between electrical and mechanical events is that, when the membrane is polarized in the usual way, the internal cellular environment favors dissociation of the actin and myosin filaments, and when a certain change has occurred in the relevant ionic gradients (see below) the train of events leading to myofibrillar shortening may begin. Whether, at a given membrane potential, the muscle does contract and how vigorously it does so depends upon many factors, each of which can appropriately be discussed separately. A review entitled Membrane potential and muscle function will, of necessity, include a dis­ cussion of matters pertaining to transmembrane electrical polarization in general, the factors responsible for maintaining the level and stability of the voltages, the effects of the transient depolarizations brought about by nerve activity, the relationship of these transient surface events to the active state in the contractile machinery, and, finally, the problem of relating mechanical changes in a single fiber to the work done by the whole muscle mass. In addi­ tion, because of the clinical orientation of the reviewer, an attempt will be made to review relevant clinical literature describing some of what is now known about the abnormalities of surface electrogenesis or contraction in some of the diseases of human muscle. As a fir&t step it will be assumed that the nerve impulse, the liberation of transmitter, and the diffusion of this substance across the neuromuscular junction are normal. Secondly, except where specified, it will be assumed that we are discussing vertebrate twitch muscle fibers, because many of the observations on striated fast muscle do not hold in the case of either cardiac (10, 11), smooth (12, 13) , arthropod (14, is), or slow muscle fibers (16) . Thirdly, it is to be emphasized that, as usual, reference to many important investigations will be omitted, as they
Caveolin-1 Upregulation Mediates Suppression of Primary Breast Tumor Growth and Brain Metastases by Stat3 Inhibition
Authors: Wen-Tai Chiu, Hsueh-Te Lee, Feng-Ju Huang, Kenneth D. Aldape, Jun Yao, Patricia S. Steeg, Cheng-Yang Chou, Zhimin Lu, Keping Xie, Suyun Huang
Journal: Cancer Research (2011)

Abstract Stat3 activation has been implicated as an important driver of brain metastasis in breast cancer, but the critical targets of Stat3 in this process are yet to be fully defined. In this study, we identified the lipid raft organizing protein Caveolin-1 (Cav-1) as a critical genetic target of Stat3 in this process. In human breast cancers, we found that activated Stat3 correlated with attenuation of Cav-1 in brain metastases relative to primary tumors. Cav-1 promoter activity and gene expression were increased by overexpressing an activated form of Stat3 but decreased by attenuation of Stat3 activity or expression. We identified putative Stat3-binding elements in the Cav-1 promoter and showed a direct repression of Cav-1 transcription by Stat3. Reciprocally, we showed that strategies to increase or decrease Cav-1 expression were sufficient to attenuate or promote breast cancer cell invasion. Furthermore, increased expression of Cav-1 phenocopied the effects of Stat3 activation in blocking primary tumor growth and abrogating formation of brain metastases. Collectively, our findings provide clinical and mechanistic evidence that Cav-1 is a critical target for suppression by Stat3 in driving invasion and metastasis of breast cancer cells. Cancer Res; 71(14); 4932–43. ©2011 AACR.
FDA imposes tougher rules on imported foods
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

The US Food and Drug Administration is imposing new regulations on both US and foreign firms that manufacture, process, pack, or hold food and drinks for human or animal consumption in the United States.

The move comes in the wake of the attacks on the United States on 11 September 2001, which raised concerns that deliberate contamination of the food supply by pathogens or harmful chemicals could lead to widespread illness or death and economic loss.

The rules, mandated by the Bioterrorism Act of …
Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial
Authors: Holger Thiele, Jochen Wöhrle, Rainer Hambrecht, Harald Rittger, Ralf Birkemeyer, Bernward Lauer, Petra Neuhaus, Oana Brosteanu, Peter Sick, Marcus Wiemer, Sebastian Kerber, Klaus Kleinertz, Ingo Eitel, Steffen Desch, Gerhard Schuler
Journal: The Lancet (2012)
Protease Gene Duplication and Proteolytic Activity in Drosophila Female Reproductive Tracts
Authors: E. S. Kelleher, J. E. Pennington
Journal: Molecular Biology and Evolution (2009)

Secreted proteases play integral roles in sexual reproduction in a broad range of taxa. In the genetic model Drosophila melanogaster, these molecules are thought to process peptides and activate enzymes inside female reproductive tracts, mediating critical postmating responses. A recent study of female reproductive tract proteins in the cactophilic fruit fly Drosophila arizonae, identified pervasive, lineage-specific gene duplication amongst secreted proteases. Here, we compare the evolutionary dynamics, biochemical nature, and physiological significance of secreted female reproductive serine endoproteases between D. arizonae and its congener D. melanogaster. We show that D. arizonae lower female reproductive tract (LFRT) proteins are significantly enriched for recently duplicated secreted proteases, particularly serine endoproteases, relative to D. melanogaster. Isolated lumen from D. arizonae LFRTs, furthermore, exhibits significant trypsin-like and elastase-like serine endoprotease acitivity, whereas no such activity is seen in D. melanogaster. Finally, trypsin- and elastase-like activity in D. arizonae female reproductive tracts is negatively regulated by mating. We propose that the intense proteolytic environment of the D. arizonae female reproductive tract relates to the extraordinary reproductive physiology of this species and that ongoing gene duplication amongst these proteases is an evolutionary consequence of sexual conflict.
Effect of donor–recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis
Authors: Mary Eapen, John P Klein, Guillermo F Sanz, Stephen Spellman, Annalisa Ruggeri, Claudio Anasetti, Maria Brown, Richard E Champlin, Joan Garcia-Lopez, Gareth Hattersely, Gesine Koegler, Mary J Laughlin, Gerard Michel, Samir K Nabhan, Franklin O Smith, Mary M Horowitz, Eliane Gluckman, Vanderson Rocha
Journal: The Lancet Oncology (2011)
Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients
Authors: Patrizia Querzoli, Massimo Pedriali, Rosa Rinaldi, Anna Rita Lombardi, Elia Biganzoli, Patrizia Boracchi, Stefano Ferretti, Claudia Frasson, Caterina Zanella, Sara Ghisellini, Federico Ambrogi, Laura Antolini, Mauro Piantelli, Stefano Iacobelli, Ettore Marubini, Saverio Alberti, Italo Nenci
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits ≤0.2 mm in diameter [pN0(i+), nanometastases] and analyzed their prognostic effect. Experimental Design: Single-institution, consecutive patients with 8 years of median follow-up (n = 702) were studied. To maximize chances of detecting micrometastases and nanometastases, whole-axilla dissections were analyzed. pN0 cases (n = 377) were systematically reevaluated by lymph node (n = 6676) step-sectioning and anticytokeratin immunohistochemical analysis. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi, and pN1 cases. Results: Minimal lymph node deposits were revealed in 13% of pN0 patients. The hazard ratio for all adverse events of pN0(i+) versus pN0(i−) was 2.51 (P = 0.00019). Hazards of pN1mi and pN0(i+) cases were not significantly different. A multivariate Cox model showed a hazard ratio of 2.16 for grouped pN0(i+)/pN1mi versus pN0(i−) (P = 0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test χ2 = 5.54, P = 0.019). Conclusion: Nanometastases are a strong risk factor for disease-free survival and for metastatic relapse. These findings support the inclusion of procedures for nanometastasis detection in tumor-node-metastasis staging.
Homologous Recombination in Agrobacterium: Potential Implications for the Genomic Species Concept in Bacteria
Authors: D. Costechareyre, F. Bertolla, X. Nesme
Journal: Molecular Biology and Evolution (2008)

According to current taxonomical rules, a bona fide bacterial species is a genomic species characterized by the genomic similarity of its members. It has been proposed that the genomic cohesion of such clusters may be related to sexual isolation, which limits gene flow between too divergent bacteria. Homologous recombination is one of the most studied mechanisms responsible for this genetic isolation. Previous studies on several bacterial models showed that recombination frequencies decreased exponentially with increasing DNA sequence divergence. In the present study, we investigated this relationship in the Agrobacterium tumefaciens species complex, which allowed us to focus on sequence divergence in the vicinity of the genetic boundaries of genomic species. We observed that the sensitivity of the recombination frequency to DNA divergence fitted a log-linear function until approximately 10% sequence divergence. The results clearly revealed that there was no sharp drop in recombination frequencies at the point where the sequence divergence distribution showed a "gap" delineating genomic species. The ratio of the recombination frequency in homogamic conditions relative to this frequency in heterogamic conditions, that is, sexual isolation, was found to decrease from 8 between the most distant strains within a species to 9 between the most closely related species, for respective increases from 4.3% to 6.4% mismatches in the marker gene chvA. This means that there was only a 1.13-fold decrease in recombination frequencies for recombination events at both edges of the species border. Hence, from the findings of this investigation, we conclude that—at least in this taxon—sexual isolation based on homologous recombination is likely not high enough to strongly hamper gene flow between species as compared with gene flow between distantly related members of the same species. The 70% relative binding ratio cutoff used to define bacterial species is likely correlated to only minor declines in homologous recombination frequencies. Consequently, the sequence diversity, as a mechanistic factor for the efficiency of recombination (as assayed in the laboratory), appears to play little role in the genetic cohesion of bacterial species, and thus, the genomic species definition for prokaryotes is definitively not reconcilable with the biological species concept for eukaryotes.