tbuckley/cabot-search huggingface dataset:
Three year follow up of a self certification system for the assessment of fitness to dive in Scotland
Authors: S Glen
Journal: British Journal of Sports Medicine (2004)

The need for routine medical examinations of sport divers in the Scottish Sub-Aqua Club (Scot-SAC) was revised in March 2000, and a new system using a self administered screening questionnaire was developed to allow divers to be assessed when necessary by doctors with diving medicine experience.To assess the effect of the new medical system on medical referee workload, diver exclusion rates, and diving incident frequency.All divers were required to complete a questionnaire to screen for conditions that might affect fitness to dive. Divers answering "Yes" to any of the questions had their medical background assessed by a diving doctor, and, if necessary, received a clinical examination or investigation. The rate of diver exclusions based on the questionnaire response was recorded in conjunction with analysis of the incident reports.The number of forms requiring review by diving doctors increased from 1.2% to 5.7% (p<0.0001, 95% confidence interval (CI) -0.06 to -0.03) in the year after the introduction of the new medical system and gradually increased in subsequent years to 7.7% (p<0.0001, 95% CI -0.08 to -0.05). The number of divers failing to be certified fit to dive increased slightly from 0.7% to 1.0% after one year (p = 0.26, 95% CI -0.01 to 0.00) and subsequently to 2.0% (p = 0.0003, 95% CI 0.02 to -0.01) after three years. Most divers were certified fit to dive on the basis of the questionnaire alone, and only 0.9% required objective investigation (such as exercise testing or echocardiography). Analysis of the incidents during three years of follow up confirmed that no incident occurred because of an undetected pre-existing medical condition. Two incidents involved divers with hypertension, but both had received medical examinations and investigation based on their responses to the questionnaire.The new self administered questionnaire system appears to be an effective screening tool for the detection of divers requiring detailed assessment by doctors with diving medicine experience.
Role of Cannabinoid Receptor CB2 in HER2 Pro-oncogenic Signaling in Breast Cancer
Authors: Eduardo Pérez-Gómez, Clara Andradas, Sandra Blasco-Benito, María M Caffarel, Elena García-Taboada, María Villa-Morales, Estefanía Moreno, Sigrid Hamann, Ester Martín-Villar, Juana M Flores, Antonia Wenners, Ibrahim Alkatout, Wolfram Klapper, Christoph Röcken, Peter Bronsert, Elmar Stickeler, Annette Staebler, Maret Bauer, Norbert Arnold, Joaquim Soriano, Manuel Pérez-Martínez, Diego Megías, Gema Moreno-Bueno, Silvia Ortega-Gutiérrez, Marta Artola, Henar Vázquez-Villa, Miguel Quintanilla, José Fernández-Piqueras, Enric I Canela, Peter J McCormick, Manuel Guzmán, Cristina Sánchez
Journal: JNCI Journal of the National Cancer Institute (2015)

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen, and Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical tests were two-sided. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis (decreased overall survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71, P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI = 0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI = 0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade and that an increased CB2 expression activates the HER2 pro-oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with prognostic value in these tumors.
Molecular Pathways: Targeting the Dependence of Mutant <i>RAS</i> Cancers on the DNA Damage Response
Authors: Elda Grabocka, Cosimo Commisso, Dafna Bar-Sagi
Journal: Clinical Cancer Research (2014)

Of the genes mutated in cancer, RAS remains the most elusive to target. Recent technological advances and discoveries have greatly expanded our knowledge of the biology of oncogenic Ras and its role in cancer. As such, it has become apparent that a property that intimately accompanies RAS-driven tumorigenesis is the dependence of RAS-mutant cells on a number of nononcogenic signaling pathways. These dependencies arise as a means of adaptation to Ras-driven intracellular stresses and represent unique vulnerabilities of mutant RAS cancers. A number of studies have highlighted the dependence of mutant RAS cancers on the DNA damage response and identified the molecular pathways that mediate this process, including signaling from wild-type Ras isoforms, ATR/Chk1, and DNA damage repair pathways. Here, we review these findings, and we discuss the combinatorial use of DNA-damaging chemotherapy with blockade of wild-type H- and N-Ras signaling by farnesyltransferase inhibitors, Chk1 inhibitors, or small-molecule targeting DNA damage repair as potential strategies through which the dependence of RAS cancers on the DNA damage response can be harnessed for therapeutic intervention.
Screening for Violence Risk in Military Veterans: Predictive Validity of a Brief Clinical Tool
Authors: Eric B. Elbogen, Michelle Cueva, H. Ryan Wagner, Shoba Sreenivasan, Mira Brancu, Jean C. Beckham, Lynn Van Male
Journal: American Journal of Psychiatry (2014)

Violence toward others is a serious problem among a subset of military veterans. The authors evaluated the predictive validity of a brief decision support tool to screen veterans for problems with violence and identify potential candidates for a comprehensive risk assessment.Data on risk factors at an initial wave and on violent behavior at 1-year follow-up were collected in two independent sampling frames: a national random-sample survey of 1,090 Iraq and Afghanistan veterans and in-depth assessments of 197 dyads of veterans and collateral informants. Risk factors (lacking money for basic needs, combat experience, alcohol misuse, history of violence and arrests, and anger associated with posttraumatic stress disorder) were chosen based on empirical support in published research. Scales measuring these risk factors were examined, and items with the most robust statistical association with outcomes were selected for the screening tool. Regression analyses were used to derive receiver operating characteristic curves of sensitivities and specificities, with area under the curve providing an index of predictive validity.The resultant 5-item screening tool, called the Violence Screening and Assessment of Needs (VIO-SCAN), yielded area-under-the-curve statistics ranging from 0.74 to 0.78 for the national survey and from 0.74 to 0.80 for the in-depth assessments, depending on level of violence analyzed.Although the VIO-SCAN does not constitute a comprehensive violence risk assessment and cannot replace fully informed clinical decision making, it is hoped that the screen will provide clinicians with a rapid, systematic method for identifying veterans at higher risk of violence, prioritizing those in need a full clinical workup, structuring review of empirically supported risk factors, and developing plans collaboratively with veterans to reduce risk and increase successful reintegration in the community.
Risk for postpartum depression associated with assisted reproductive technologies and multiple births: a systematic review
Authors: Lori E. Ross, Karen McQueen, Simone Vigod, Cindy-Lee Dennis
Journal: Human Reproduction Update (2010)

BACKGROUNDIt has been hypothesized that certain obstetrical populations, including women who conceive using assisted reproductive technologies (ART) and women with multiple births, may be at increased risk for postpartum depression. In this systematic literature review, we examine the published evidence for this hypothesis.
ASSOCIATION BETWEEN VILLOUS ATROPHY IN RHEUMATOID ARTHRITIS AND A RHEUMATOID FACTOR AND GLIADIN-SPECIFIC IgG
Authors: Cliona O'Farrelly, D. Melcher, R. Price, R. Sherwood, D. Marten, B. McDougall, A.J. Goldstein, L. Fernandes
Journal: The Lancet (1988)
Pentachlorophenol and Cancer Risk: Focusing the Lens on Specific Chlorophenols and Contaminants
Authors: Glinda S. Cooper, Samantha Jones
Journal: Environmental Health Perspectives (2008)

Pentachlorophenol, a fungicide widely used as a wood preservative, was classified in 1999 by the International Agency for Research on Cancer as a possible human carcinogen. We reviewed currently available data to determine the extent to which recent studies assist in distinguishing the effect of pentachlorophenol from that of its contaminants (e.g., dioxins and other chlorophenols).We performed a systematic review of published studies pertaining to cancer risk in relation to pentachlorophenol exposure, focusing on results pertaining specifically to all cancer sites and specific hematopoietic cancers, and data pertaining to risks associated with other types of chlorophenols, dioxins, or furans.The pentachlorophenol studies presented considerable evidence pertaining to hematopoietic cancers, with strong associations seen in multiple studies, in different locations, and using different designs. There is little evidence of an association between these cancers and chlorophenols that contain fewer than four chlorines. The extension of a large cohort study of sawmill workers, with follow-up to 1995, provided information about risks of relatively rare cancers (e.g., non-Hodgkin lymphoma, multiple myeloma), using a validated exposure assessment procedure that distinguishes between exposures to pentachlorophenol and tetrachlorophenol. In contrast with dioxin, pentachlorophenol exposure has not been associated with total cancer incidence or mortality.The updated cohort study focusing on pentachlorophenol provides increased statistical power and precision, and demonstrates associations between hematopoietic cancer and pentachlorophenol exposure not observed in earlier evaluations of this cohort. Contaminant confounding is an unlikely explanation for the risks seen with pentachlorophenol exposure.
Early and late results of surgical repair of truncus arteriosus.
Authors: C Marcelletti, D C McGoon, G K Danielson, R B Wallace, D D Mair
Journal: Circulation (1977)

Ninety-two patients had corrective operation for truncus arteriosus between 1967 and 1975. During the first 30 days after surgery, 23 patients died. No significant differences appear between early mortality and sex, type of truncus, variations in pulmonary arterial anatomy, truncal valve regurgitation, associated anomalies, previous operation, or duration of extracorporeal circulation. Greater risk is probably encountered with the higher but still operable levels of pulmonary resistance. Reoperation has been required in three patients. Fifty-nine percent of survivors are symptom-free, with all but two of the remainder (38%) being in NYHA functional class II. The late result is suggestively less satisfactory in patients with significant preoperative truncal valve regurgitation. Some late complications related to deterioration of the earlier aortic homograft conduit may be avoided by use of a porcine valve Dacron conduit. The current operative mortality of 9%, and the well-being of 97% of surviving patients suggest the continued advisability of recommending operation for appropriate patients.
Serum factor affecting neutrophil function during acute viral hepatitis.
Authors: S J Saunders, E B Dowdle, C Fiskerstrand, M Bassendine, R Walls
Journal: Gut (1978)

Sera from eight of 17 patients with acute viral hepatitis was deficient in its ability to support neutrophil bactericidal function in vitro. This defect appeared to be related to the viral infection itself. Sera from patients with drug hepatitis or mechanical obstructive jaundice did not show this effect.
Mixed allergic bronchopulmonary fungal disease due to Pseudallescheria boydii and Aspergillus.
Authors: F R Lake, A E Tribe, R McAleer, J Froudist, P J Thompson
Journal: Thorax (1990)

A 24 year old asthmatic woman with mixed allergic bronchopulmonary fungal disease due to Pseudallescheria boydii and Aspergillus is reported. No previous cases due to P boydii have been described. This patient provides evidence that fungi other than Aspergillus species may cause the condition.
Prejunctional and postjunctional actions of endogenous norepinephrine at the sympathetic neuroeffector junction in canine coronary arteries.
Authors: R A Cohen, J T Shepherd, P M Vanhoutte
Journal: Circulation Research (1983)

The effects of endogenous and of exogenous norepinephrine were studied in isolated rings of canine left circumflex coronary artery and its first ventricular branch. Norepinephrine was released from adrenergic nerve endings by transmural electrical stimulation and by tyramine. In rings contracted with prostaglandin F2 alpha, transmural electrical stimulation resulted in frequency-dependent relaxations which were blocked by propranolol or tetrodotoxin; tyramine and exogenous norepinephrine caused concentration-dependent relaxations which were blocked by propranolol. The tyramine-induced relaxations also were inhibited by cocaine. The left circumflex artery was less sensitive than its branch to beta-adrenergic activation; this difference was significant even between rings of the two vessels immediately adjacent to the branching point and was abolished by phentolamine. In the presence of propranolol, transmural electrical stimulation, tyramine and phenylephrine, produced contractions of the left circumflex artery, but not the branch; these contractions were prevented by phentolamine. Phentolamine, but not prazosin, augmented the beta-adrenergic response of left circumflex artery to low frequency stimulation; in arteries preincubated with 3H-norepinephrine, this was accompanied by an increased overflow of tritiated neurotransmitter. The prejunctional effect of phentolamine was also evident in branch coronary arteries which exhibit no postjunctional alpha-adrenergic responses. With high frequency stimulation, both alpha-adrenergic antagonists equally augmented the relaxation of left circumflex artery; the efflux of tritiated norepinephrine was not different from untreated arteries. These experiments demonstrate, in isolated coronary arteries, that the primary adrenergic response to released endogenous norepinephrine is beta-adrenergic relaxation. The prejunctional effects of nonspecific alpha-adrenergic antagonists preclude their use in determining the importance of postjunctional coronary alpha-adrenergic receptor activation caused by sympathetic nerve stimulation.
Differences Between Left and Right Ventricular Chamber Geometry Affect Cardiac Vulnerability to Electric Shocks
Authors: Blanca Rodríguez, Li Li, James C. Eason, Igor R. Efimov, Natalia A. Trayanova
Journal: Circulation Research (2005)

Although effects of shock strength and waveform on cardiac vulnerability to electric shocks have been extensively documented, the contribution of ventricular anatomy to shock-induced polarization and postshock propagation and thus, to shock outcome, has never been quantified; this is caused by lack of experimental methodology capable of mapping 3-D electrical activity. The goal of this study was to use optical imaging experiments and 3-D bidomain simulations to investigate the role of structural differences between left and right ventricles in vulnerability to electric shocks in rabbit hearts. The ventricles were paced apically, and uniform-field, truncated-exponential, monophasic shocks of reversed polarity were applied over a range of coupling intervals (CIs) in experiment and model. Experiments and simulations revealed that reversing the direction of externally-applied field (RV- or LV- shocks) alters the shape of the vulnerability area (VA), the 2-D grid encompassing episodes of arrhythmia induction. For RV- shocks, VA was nearly rectangular indicating little dependence of postshock arrhythmogenesis on CI. For LV- shocks, the probability of arrhythmia induction was higher for longer than for shorter CIs. The 3-D simulations demonstrated that these effects stem from the fact that reversal of field direction results in relocation of the main postshock excitable area from LV wall (RV- shocks) to septum (LV- shocks). Furthermore, the effect of septal (but not LV) excitable area in postshock propagation was found to strongly depend on preshock state. Knowledge regarding the location of the main postshock excitable area within the 3-D ventricular volume could be important for improving defibrillation efficacy.
Evasion of Phagocytosis through Cooperation between Two Ligand-binding Regions in <i>Streptococcus pyogenes</i> M Protein
Authors: Fredric Carlsson, Karin Berggård, Margaretha Stålhammar-Carlemalm, Gunnar Lindahl
Journal: The Journal of Experimental Medicine (2003)

The M protein of Streptococcus pyogenes is a major bacterial virulence factor that confers resistance to phagocytosis. To analyze how M protein allows evasion of phagocytosis, we used the M22 protein, which has features typical of many M proteins and has two well-characterized regions binding human plasma proteins: the hypervariable NH2-terminal region binds C4b-binding protein (C4BP), which inhibits the classical pathway of complement activation; and an adjacent semivariable region binds IgA-Fc. Characterization of chromosomal S. pyogenes mutants demonstrated that each of the ligand-binding regions contributed to phagocytosis resistance, which could be fully explained as cooperation between the two regions. Deposition of complement on S. pyogenes occurred almost exclusively via the classical pathway, even under nonimmune conditions, but was down-regulated by bacteria-bound C4BP, providing an explanation for the ability of bound C4BP to inhibit phagocytosis. Different opsonizing antisera shared the ability to block binding of both C4BP and IgA, suggesting that the two regions in M22 play important roles also under immune conditions, as targets for protective antibodies. These data indicate that M22 and similar M proteins confer resistance to phagocytosis through ability to bind two components of the human immune system.
Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study
Authors: M. Ranson, M. Reck, A. Anthoney, A.-R. Hanauske, E. Dean, I. Melezinek, G. Klingelschmitt, H. Kletzl, J. Blatter, C. Twelves
Journal: Annals of Oncology (2010)
Color realism revisited
Authors: Alex Byrne, David R. Hilbert
Journal: Behavioral and Brain Sciences (2003)

Our reply is in four parts. The first part, R1, addresses objections to our claim that there might be “unknowable” color facts. The second part, R2, discusses the use we make of opponent process theory. The third part, R3, examines the question of whether colors are causes. The fourth part, R4, takes up some issues concerning the content of visual experience.
The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis
Authors: Chand Khanna, Xiaolin Wan, Seuli Bose, Ryan Cassaday, Osarenoma Olomu, Arnulfo Mendoza, Choh Yeung, Richard Gorlick, Stephen M Hewitt, Lee J Helman
Journal: Nature Medicine (2004)
Changes in expression of membrane TNF, NF-κB activation and neutrophil apoptosis during active and resolved inflammation
Authors: Helen L Wright, Batsi Chikura, Roger C Bucknall, Robert J Moots, Steven W Edwards
Journal: Annals of the Rheumatic Diseases (2010)

Background Tumour necrosis factor (TNF) is central to the pathophysiological process of rheumatoid arthritis (RA), whether as soluble cytokine or membrane-expressed pro-TNF (mTNF). Objectives To determine whether neutrophils, which can express TNF, are activated in the blood of patients with RA compared with healthy controls. To investigate, by focusing on mTNF expression, if the functions of RA neutrophils change in response to therapeutic TNF inhibition. Methods TNF was measured by flow cytometry and qPCR in neutrophils from 20 patients with RA before and after the start of TNF inhibitor therapy. Apoptosis was measured by morphology, and western blotting of pro- and antiapoptotic proteins in cell lysates. Nuclear factor κB (NF-κB) activation was determined by western blotting of phosphorylated NF-κB (p65). Results Before treatment RA neutrophils exhibited increased TNF mRNA expression, elevated mTNF levels and NF-κB activity compared with controls. They also underwent delayed apoptosis as shown by altered expression of anti- and proapoptotic proteins, such as Mcl-1 and caspases. Neutrophil TNF expression returned to baseline levels during successful treatment with anti-TNF biological agents, and there was a close correlation between clinical disease improvement and changes in neutrophil function. Conclusions Neutrophils express elevated levels of TNF in RA and the transcription factor, NF-κB, a target of TNF, is activated. This mechanism could lead to a self-sustained inflammatory process. These data point to an important role of neutrophils in the abnormal TNF signalling pathways activated in RA and provide new evidence that neutrophils actively contribute to altered cytokine signalling in inflammatory diseases.