859 research outputs found

    Resistant Somatoform Symptoms: Try CBT and Antidepressants. Preferred Strategy for β€˜Mismatched’ Category of Illnesses.

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    This articles describes: debate about how to categorize somatoform disorders--as psychological or physiologic evidence supporting psychotherapy and antidepressants to help patients with treatment-resistant somatoform disorders

    The Revised Emotional Intelligence Scale: Cross Cultural Validation in a Turkish Psychiatric Outpatient Cohort

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    The original Emotional Intelligence Scale of Fukunishi utilized 65 items, measuring three basic dimensions: Intrapersonal, Interpersonal and Situational. Subsequently, using a sample of 170 U.S.psychiatric outpatients, it was factor reduced from 65 to 34 items that showed excellent internal consistency both overall and for two of its three hypothesized factors. This study examined the internal consistency of the 34-item solution in a cohort of 123 Turkish psychiatric outpatients. The mean age of the sample was 34.5 years (SD=11.2). The internal consistency of the total scale was 0.91. Scores also were high for the Interpersonal dimension (0.90) and the Intrapersonal dimension (.0.84), but not for the Situational dimension (0.67). A similar lower scoring pattern for the Si- tuational dimension has been seen both in US and Japanese outpatient populations. These data suggest that, in a Turkish psychiatric outpatient population, this scale also appears to maintain excellent internal consistency both overall and for two of its three hypothesized factors. This inventory may be suitable to investigate suitability for psychological treatment

    How Low Can We Go?: Comparing Long-term Oncologic Outcomes for APR and LAR in Very Low Rectal Cancer

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    Management of very low rectal cancer is one of the most challenging issues faced by colorectal surgeons. For tumors in the mid and upper rectum, procedures can be done to resect the cancer while maintaining continence, a major determinant of post-operative quality of life. In the low rectum, however, to optimize oncologic outcomes, many surgeons feel compelled to pursue abdominoperineal (APR) over low anterior resection (LAR), a sphincter-preserving procedure. It was hypothesized that after robust adjustment, procedure choice will not be associated with a difference in disease-free survival in the resection of tumors in the low rectum. To analyze this, the US Rectal Cancer Collaborative Database, a comprehensive, multi-center dataset obtained from six institutions between 2010 and 2016, was queried. Patients undergoing TME resection for Stage I-III very low rectal cancers (involvement) were selected for this study. Patients were categorized by procedure- LAR vs APR. Primary outcome was five-year disease-free survival. Secondary outcomes included overall survival, recurrence, length of stay, and complications. An adjusted analysis was performed to account for all known potential confounders. 431 patients with very low rectal cancer treated by either APR or LAR were identified. 154 (35.7%) underwent APR. The overall recurrence rate was 19.6%. Median follow-up time was 42.5 months. An analysis adjusted for age, gender, BMI, ASA class, and pathologic stage observed no difference in disease free survival between operative types (HR=0.90, 95% CI [0.53-1.52], p=0.70). Similarly, secondary outcomes demonstrated no significant difference between operation types, including length of stay (Beta: 0.04, Std. error = 0.25, p = 0.54), overall survival (HR=1.29, 95% CI [0.71-2.32], p=0.39), or complications (OR = 1.53, 95% CI [0.94 - 2.50], p=0.09). In this analysis, no significant difference in disease-free survival or overall survival was observed between patients undergoing APR or LAR for very low rectal cancer. This comprehensive study supports the treatment of very low rectal cancer, less than 5cm from the anorectal ring with no sphincter involvement, by either abdominal perineal or low anterior resection. Further studies may focus on patient-reported and quality of life outcomes which may influence decision-making

    Homeostatic competition drives tumor growth and metastasis nucleation

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    We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa

    Making Neural Networks FAIR

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    Research on neural networks has gained significant momentum over the past few years. Because training is a resource-intensive process and training data cannot always be made available to everyone, there has been a trend to reuse pre-trained neural networks. As such, neural networks themselves have become research data. In this paper, we first present the neural network ontology FAIRnets Ontology, an ontology to make existing neural network models findable, accessible, interoperable, and reusable according to the FAIR principles. Our ontology allows us to model neural networks on a meta-level in a structured way, including the representation of all network layers and their characteristics. Secondly, we have modeled over 18,400 neural networks from GitHub based on this ontology, which we provide to the public as a knowledge graph called FAIRnets, ready to be used for recommending suitable neural networks to data scientists

    Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

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    Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. Β© 2013 D'Armiento et al

    Congenital Cytomegalovirus Mortality in the United States, 1990–2006

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    Cytomegalovirus (CMV) is a member of the herpes family of viruses, which is transmitted by sexual and non-sexual contact. Human CMV causes a wide variety of infection and illness in healthy adults, in those with compromised immune systems (such as AIDS), in those with cardiovascular disease, and in pregnant women who can pass the infection to their unborn child (congenital CMV). Treatment options for congenital CMV are limited and no effective vaccine to protect against CMV currently exists. Previous studies have demonstrated that African Americans and Mexican Americans are at an increased risk for congenital CMV infections. In this study, the authors examined death certificate data of US Residents from 1990–2006 in which congenital CMV was listed as one of the diagnoses at death. The analysis demonstrated that there is a significant burden of congenital CMV deaths in infants (<1 year old) with African Americans and Native Americans overrepresented. This study helps quantify congenital CMV deaths among US residents and adds further support to the importance of funding CMV vaccine research

    Identification of a novel splice variant form of the influenza a virus m2 ion channel with an antigenically distinct ectodomain

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    Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle

    Two Prp19-Like U-Box Proteins in the MOS4-Associated Complex Play Redundant Roles in Plant Innate Immunity

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    Plant Resistance (R) proteins play an integral role in defense against pathogen infection. A unique gain-of-function mutation in the R gene SNC1, snc1, results in constitutive activation of plant immune pathways and enhanced resistance against pathogen infection. We previously found that mutations in MOS4 suppress the autoimmune phenotypes of snc1, and that MOS4 is part of a nuclear complex called the MOS4-Associated Complex (MAC) along with the transcription factor AtCDC5 and the WD-40 protein PRL1. Here we report the immuno-affinity purification of the MAC using HA-tagged MOS4 followed by protein sequence analysis by mass spectrometry. A total of 24 MAC proteins were identified, 19 of which have predicted roles in RNA processing based on their homology to proteins in the Prp19-Complex, an evolutionarily conserved spliceosome-associated complex containing homologs of MOS4, AtCDC5, and PRL1. Among these were two highly similar U-box proteins with homology to the yeast and human E3 ubiquitin ligase Prp19, which we named MAC3A and MAC3B. MAC3B was recently shown to exhibit E3 ligase activity in vitro. Through reverse genetics analysis we show that MAC3A and MAC3B are functionally redundant and are required for basal and R protein–mediated resistance in Arabidopsis. Like mos4-1 and Atcdc5-1, mac3a mac3b suppresses snc1-mediated autoimmunity. MAC3 localizes to the nucleus and interacts with AtCDC5 in planta. Our results suggest that MAC3A and MAC3B are members of the MAC that function redundantly in the regulation of plant innate immunity
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