tbuckley/cabot-search huggingface dataset:
Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables
Authors: Vera Panzarella, Giuseppe Pizzo, Francesco Calvino, Domenico Compilato, Giuseppe Colella, Giuseppina Campisi
Journal: International Journal of Oral Science (2013)

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC), the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC (mean age: 62 years, M/F: 2.39∶1) were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included: sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges: dichotomous (≤1 month vs. >1 month) and polytomous (<1 month, 1-3 months, >3 months) delay. Data were investigated by univariate and multivariate analyses and a P value ≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were: 'Personal experience of cancer' (dichotomous delay: P=0.05, odds ratio (OR)=0.33, 95% confidence interval (CI)=0.11-0.99; polytomous delay: P=0.006, Chi-square=10.224) and 'Unawareness' (dichotomous delay: P<0.01, OR=4.96, 95% CI=2.16-11.37; polytomous delay: P=0.087, Chi-square=4.77). Also 'Denial' (P<0.01, OR=6.84, 95% CI=2.31-20.24) and 'Knowledge of cancer' (P=0.079, Chi-square=8.359) were found to be statistically significant both for dichotomous and for polytomous categorization of delay, respectively. The findings of this study indicated that, in the investigated cohorts, the knowledge about cancer issues is strongly linked to the patient delay. Educational interventions on the Mediterranean population are necessary in order to increase the patient awareness and to emphasize his/her key role in early diagnosis of OSCC.
Caring for Critically Ill Patients with Ebola Virus Disease. Perspectives from West Africa
Authors: Robert A. Fowler, Thomas Fletcher, William A. Fischer, Francois Lamontagne, Shevin Jacob, David Brett-Major, James V. Lawler, Frederique A. Jacquerioz, Catherine Houlihan, Tim O’Dempsey, Mauricio Ferri, Takuya Adachi, Marie-Claire Lamah, Elhadj Ibrahima Bah, Thierry Mayet, John Schieffelin, Susan L. McLellan, Mikiko Senga, Yasuyuki Kato, Christophe Clement, Simon Mardel, Rosa Constanza Vallenas Bejar De Villar, Nahoko Shindo, Daniel Bausch
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.
PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation
Authors: Cristiana Guiducci, Cristina Ghirelli, Marie-Annick Marloie-Provost, Tracy Matray, Robert L. Coffman, Yong-Jun Liu, Franck J. Barrat, Vassili Soumelis
Journal: The Journal of Experimental Medicine (2008)

Plasmacytoid predendritic cells (pDCs) are the main producers of type I interferon (IFN) in response to Toll-like receptor (TLR) stimulation. Phosphatidylinositol-3 kinase (PI3K) has been shown to be activated by TLR triggering in multiple cell types; however, its role in pDC function is not known. We show that PI3K is activated by TLR stimulation in primary human pDCs and demonstrate, using specific inhibitors, that PI3K is required for type I IFN production by pDCs, both at the transcriptional and protein levels. Importantly, PI3K was not involved in other proinflammatory responses of pDCs, including tumor necrosis factor alpha and interleukin 6 production and DC differentiation. pDCs preferentially expressed the PI3K delta subunit, which was specifically involved in the control of type I IFN production. Although uptake and endosomal trafficking of TLR ligands were not affected in the presence of PI3K inhibitors, there was a dramatic defect in the nuclear translocation of IFN regulatory factor (IRF) 7, whereas nuclear factor kappaB activation was preserved. Thus, PI3K selectively controls type I IFN production by regulating IRF-7 nuclear translocation in human pDCs and could serve as a novel target to inhibit pathogenic type I IFN in autoimmune diseases.
DNA Methylation is Associated with an Increased Level of Conservation at Nondegenerate Nucleotides in Mammals
Authors: Trees-Juen Chuang, Feng-Chi Chen
Journal: Molecular Biology and Evolution (2013)

DNA methylation at CpG dinucleotides can significantly increase the rate of cytosine-to-thymine mutations and the level of sequence divergence. Although the correlations between DNA methylation and genomic sequence evolution have been widely studied, an unaddressed yet fundamental question is how DNA methylation is associated with the conservation of individual nucleotides in different sequence contexts. Here, we demonstrate that in mammalian exons, the correlations between DNA methylation and the conservation of individual nucleotides are dependent on the type of exonic sequence (coding or untranslated), the degeneracy of coding nucleotides, background selection pressure, and the relative position (first or nonfirst exon in the transcript) where the nucleotides are located. For untranslated and nonzero-fold degenerate nucleotides, methylated sites are less conserved than unmethylated sites regardless of background selection pressure and the relative position of the exon. For zero-fold degenerate (or nondegenerate) nucleotides, however, the reverse trend is observed in nonfirst coding exons and first coding exons that are under stringent background selection pressure. Furthermore, cytosine-to-thymine mutations at methylated zero-fold degenerate nucleotides are predicted to be more detrimental than those that occur at unmethylated nucleotides. As zero-fold and nonzero-fold degenerate nucleotides are very close to each other, our results suggest that the "functional resolution" of DNA methylation may be finer than previously recognized. In addition, the positive correlation between CpG methylation and the level of conservation at zero-fold degenerate nucleotides implies that CpG methylation may serve as an "indicator" of functional importance of these nucleotides.
High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers
Authors: Amy L.S. Tai, William Mak, Phoebe K.M. Ng, Daniel T.T. Chua, Mandy Y.M. Ng, Li Fu, Kevin K.W. Chu, Yan Fang, You Qiang Song, Muhan Chen, Minyue Zhang, Pak C. Sham, Xin-Yuan Guan
Journal: Cancer Research (2006)

Abstract Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non–small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is ∼180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer. (Cancer Res 2006; 66(8): 4133-8)
Ryanodine does not affect calcium current in guinea pig ventricular myocytes in which Ca2+ is buffered.
Authors: C W Balke, W G Wier
Journal: Circulation Research (1991)

Calcium current in mammalian ventricular muscle is altered in the presence of ryanodine. Previous studies performed on rat ventricular cells have shown a slowing of Ca2+ current inactivation and suggest the hypothesis that ryanodine, by reducing the release of Ca2+ from the sarcoplasmic reticulum, reduces the availability of Ca2+ for inactivation of Ca2+ current (Ca(2+)-dependent inactivation). Another hypothesis is that the effects of ryanodine on Ca2+ current are due to a mechanical connection of the ryanodine receptor with the L-type Ca2+ channel. To further test these hypotheses we examined the effect of ryanodine on Ca2+ current in single voltage-clamped guinea pig ventricular myocytes that contained Ca2+ indicator and Ca2+ buffer. We used fura 2 (pentapotassium salt) to confirm that the ryanodine we used was capable of abolishing Ca2+ release from the sarcoplasmic reticulum during the period in which it was present. We perfused the cells with 10 mM EGTA to block changes in intracellular Ca2+ concentration. In the absence of internal EGTA, Ca2+ currents displayed biexponential inactivation and Ca(2+)-dependent inactivation (steady-state inactivation curves turned up at positive potentials). Inactivation was slowed by ryanodine at 10 microM. In cells perfused internally with EGTA, however, ryanodine had no effects, and steady-state inactivation curves were not shifted to the right. We conclude that, in guinea pig ventricular myocytes, the effects of ryanodine on Ca2+ current are mediated by Ca2+ and thus the effects of ryanodine do not provide a basis on which to postulate a physical connection between the L-type Ca2+ channel and the ryanodine receptor (sarcoplasmic reticulum Ca2+ release channel).
Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study
Authors: U Klaassen, H Wilke, A Harstrick, C Philippou Pari, D Strumberg, K Neumann, W Eberhardt, W Achterrath, L Lenaz, S Seeber
Journal: Annals of Oncology (1998)
A Randomized Trial of Integrated Group Therapy Versus Group Drug Counseling for Patients With Bipolar Disorder and Substance Dependence
Authors: Roger D. Weiss, Margaret L. Griffin, Monika E. Kolodziej, Shelly F. Greenfield, Lisa M. Najavits, Dennis C. Daley, Heidi Ray Doreau, John A. Hennen
Journal: American Journal of Psychiatry (2007)

Objective: Although bipolar disorder and substance use disorder frequently co-occur, there is little information on the effectiveness of behavioral treatment for this population. Integrated group therapy, which addresses the two disorders simultaneously, was compared with group drug counseling, which focuses on substance use. The authors hypothesized that patients receiving integrated group therapy would have fewer days of substance use and fewer weeks ill with bipolar disorder. Method: A randomized controlled trial compared 20 weeks of integrated group therapy or group drug counseling with 3 months of posttreatment follow-up. Sixty-two patients with bipolar disorder and current substance dependence, treated with mood stabilizers for ≥2 weeks, were randomly assigned to integrated group therapy (N=31) or group drug counseling (N=31). The primary outcome measure was the number of days of substance use. The primary mood outcome was the number of weeks ill with a mood episode. Results: Intention-to-treat analysis revealed significantly fewer days of substance use for integrated group therapy patients during treatment and follow-up. Groups were similar in the number of weeks ill with bipolar disorder during treatment and follow-up, although integrated group therapy patients had more depressive and manic symptoms. Conclusions: Integrated group therapy, a new treatment developed specifically for patients with bipolar disorder and substance dependence, appears to be a promising approach to reduce substance use in this population.
More than 50% of players sustained a time-loss injury (&gt;1 day of lost training or playing time) during the 2012 Super Rugby Union Tournament: a prospective cohort study of 17 340 player-hours
Authors: Martin P Schwellnus, Alan Thomson, Wayne Derman, Esme Jordaan, Clint Readhead, Rob Collins, Ian Morris, Org Strauss, Ewoudt Van der Linde, Arthur Williams
Journal: British Journal of Sports Medicine (2014)

Background Professional Rugby Union is a contact sport with a high risk of injury. Objective To document the incidence and nature of time-loss injuries during the 2012 Super Rugby tournament. Design Prospective cohort study. Setting 2012 Super Rugby tournament (Australia, New Zealand, South Africa). Participants 152 players from 5 South African teams. Methods Team physicians collected daily injury data through a secure, web-based electronic platform. Data included size of the squad, type of day, main player position, training or match injury, hours of play (training and matches), time of the match injury, mechanism of injury, main anatomical location of the injury, specific anatomical structure of the injury, the type of injury, the severity of the injury (days lost). Results The proportion (%) of players sustaining a time-loss injury during the tournament was 55%, and 25% of all players sustained &gt;1 injury. The overall incidence rate (IR/1000 player-hours) of injuries was 9.2. The IR for matches (83.3) was significantly higher than for training (2.1) and the IR was similar for forwards and backs. Muscle/tendon (50%) and joint/ligament (32.7%) injuries accounted for &gt;80% of injuries. Most injuries occurred in the lower (48.1%) and upper limb (25.6%). 42% of all injuries were moderate (27.5%) or severe (14.8%), and tackling (26.3%) and being tackled (23.1%) were the most common mechanisms of injury. The IR of injuries was unrelated to playing at home compared with away (locations ≥6 h time difference). Conclusions 55% of all players were injured during the 4-month Super Rugby tournament (1.67 injuries/match). Most injuries occurred in the lower (knee, thigh) or upper limb (shoulder, clavicle). 42% of injuries were severe enough for players to not play for &gt;1 week.
miR-335 Directly Targets Rb1 (pRb/p105) in a Proximal Connection to p53-Dependent Stress Response
Authors: Michele Scarola, Stefan Schoeftner, Claudio Schneider, Roberta Benetti
Journal: Cancer Research (2010)

Loss-of-function mutations of retinoblastoma family (Rb) proteins drive tumorigenesis by overcoming barriers to cellular proliferation. Consequently, factors modulating Rb function are of great clinical import. Here, we show that miR-335 is differentially expressed in human cancer cells and that it tightly regulates the expression of Rb1 (pRb/p105) by specifically targeting a conserved sequence motif in its 3' untranslated region. We found that by altering Rb1 (pRb/p105) levels, miR-335 activates the p53 tumor suppressor pathway to limit cell proliferation and neoplastic cell transformation. DNA damage elicited an increase in miR-335 expression in a p53-dependent manner. miR-335 and p53 cooperated in a positive feedback loop to drive cell cycle arrest. Together, these results indicate that miR-335 helps control proliferation by balancing the activities of the Rb and p53 tumor suppressor pathways. Further, they establish that miR-335 activation plays an important role in the induction of p53-dependent cell cycle arrest after DNA damage.
New contract pushes up cost of GP care in Scotland
Authors: B. Christie
Journal: BMJ (2008)

The cost of care provided by GPs in Scotland has risen by 40% since the new GP contract was introduced in 2004. Total NHS Scotland spending rose by just under 28% in the same period.

The extra costs resulted in a £160m (€200m; $320m) overspend in the first three years of the contract, which NHS Scotland’s boards have had to meet out of their own budgets. The biggest factor was an underestimate of the number of GPs who would qualify for incentive payments under the quality and outcomes framework (QOF). The Scottish health department estimated that 80% …
Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain
Authors: Elizabeth A. Old, Suchita Nadkarni, John Grist, Clive Gentry, Stuart Bevan, Ki-Wook Kim, Adrian J. Mogg, Mauro Perretti, Marzia Malcangio
Journal: Journal of Clinical Investigation (2014)

A major dose-limiting side effect associated with cancer-treating antineoplastic drugs is the development of neuropathic pain, which is not readily relieved by available analgesics. A better understanding of the mechanisms that underlie pain generation has potential to provide targets for prophylactic management of chemotherapy pain. Here, we delineate a pathway for pain that is induced by the chemotherapeutic drug vincristine sulfate (VCR). In a murine model of chemotherapy-induced allodynia, VCR treatment induced upregulation of endothelial cell adhesion properties, resulting in the infiltration of circulating CX3CR1⁺ monocytes into the sciatic nerve. At the endothelial-nerve interface, CX3CR1⁺ monocytes were activated by the chemokine CX3CL1 (also known as fractalkine [FKN]), which promoted production of reactive oxygen species that in turn activated the receptor TRPA1 in sensory neurons and evoked the pain response. Furthermore, mice lacking CX3CR1 exhibited a delay in the development of allodynia following VCR administration. Together, our data suggest that CX3CR1 antagonists and inhibition of FKN proteolytic shedding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for the prophylactic treatment of chemotherapy-induced pain.
Internal impingement in the tennis player: rehabilitation guidelines
Authors: A M Cools, G Declercq, B Cagnie, D Cambier, E Witvrouw
Journal: British Journal of Sports Medicine (2007)

Internal impingement is a commonly described cause of shoulder pain in the overhead athlete, particularly in tennis players. Three shoulder dysfunctions, often correlated with internal impingement symptoms, require attention in the rehabilitation strategy of internal impingement in the tennis player: (1) acquired glenohumeral anterior instability, (2) loss of internal rotation range of motion, and (3) lack of retraction strength. Based on recent literature, the following guidelines are proposed in the rehabilitation of the tennis player with internal impingement symptoms: (1) shoulder rehabilitation should be integrated into kinetic chain training, not only in the advanced phases of the athlete's rehabilitation, but from the initial phases; (2) both angular and translational mobilisations can be used in the treatment of acquired loss of glenohumeral internal rotation range of motion to stretch the posterior structures of the glenohumeral joint; and 3) in the rehabilitation of scapular dyskinesis, the therapist should focus on restoration of intramuscular trapezius muscle balance in the scapular exercises, with special attention to strength training of the retractors.
Brain tumor classification using the diffusion tensor image segmentation (D-SEG) technique
Authors: T. L. Jones, T. J. Byrnes, G. Yang, F. A. Howe, B. A. Bell, T. R. Barrick
Journal: Neuro-Oncology (2014)

There is an increasing demand for noninvasive brain tumor biomarkers to guide surgery and subsequent oncotherapy. We present a novel whole-brain diffusion tensor imaging (DTI) segmentation (D-SEG) to delineate tumor volumes of interest (VOIs) for subsequent classification of tumor type. D-SEG uses isotropic (p) and anisotropic (q) components of the diffusion tensor to segment regions with similar diffusion characteristics.DTI scans were acquired from 95 patients with low- and high-grade glioma, metastases, and meningioma and from 29 healthy subjects. D-SEG uses k-means clustering of the 2D (p,q) space to generate segments with different isotropic and anisotropic diffusion characteristics.Our results are visualized using a novel RGB color scheme incorporating p, q and T2-weighted information within each segment. The volumetric contribution of each segment to gray matter, white matter, and cerebrospinal fluid spaces was used to generate healthy tissue D-SEG spectra. Tumor VOIs were extracted using a semiautomated flood-filling technique and D-SEG spectra were computed within the VOI. Classification of tumor type using D-SEG spectra was performed using support vector machines. D-SEG was computationally fast and stable and delineated regions of healthy tissue from tumor and edema. D-SEG spectra were consistent for each tumor type, with constituent diffusion characteristics potentially reflecting regional differences in tissue microstructure. Support vector machines classified tumor type with an overall accuracy of 94.7%, providing better classification than previously reported.D-SEG presents a user-friendly, semiautomated biomarker that may provide a valuable adjunct in noninvasive brain tumor diagnosis and treatment planning.
IgM, IgG, and IgA synthesis in vitro in persons suffering from yersinia arthritis and in patients with ankylosing spondylitis.
Authors: R Vuento, J Eskola, R Leino, S Koskimies, M Viander
Journal: Annals of the Rheumatic Diseases (1984)

In ankylosing spondylitis (AS) and in yersinia arthritis the main findings in serum immunoglobulin (Ig) studies have been raised IgA in AS and a high anti-yersinia IgA and IgG response and the persistence of IgA class antibodies in yersinia arthritis. In order to study predisposition to high IgA response in AS and yersinia arthritis we measured the in-vitro Ig production in patients with AS and in persons who have once had yersinia arthritis, and we compared it with the Ig production in persons who have had yersiniosis but recovered without getting arthritis and with that in healthy controls. IgA secretion by peripheral blood lymphocytes stimulated by pokeweed mitogen was the same in all 4 groups, and no signs of higher IgA production in AS patients could be found. In AS patients lymphocyte activation by whole yersinia bacteria resulted in higher total IgG production than in healthy controls. The total number of plaque-forming cells in yersinia-stimulated cultures was significantly higher in persons who have had yersiniosis without arthritis than in persons who have suffered from yersinia arthritis or in persons in other groups. AS patients had low IgM production, which reverted to normal when hydrocortisone was added to the culture. The in-vitro Ig production in general did not correlate with the presence of the HLA B27 antigen but rather with the clinical history of the subjects studied.