Miracle-dz/UniFAR-FTUs huggingface dataset:
Activated Phosphoinositide 3-Kinase/AKT Signaling Confers Resistance to Trastuzumab but not Lapatinib

Trastuzumab and lapatinib provide clinical benefit to women with human epidermal growth factor receptor 2 (HER)–positive breast cancer. However, not all patients whose tumors contain the HER2 alteration respond. Consequently, there is an urgent need to identify new predictive factors for these agents. The aim of this study was to investigate the role of receptor tyrosine kinase signaling and phosphoinositide 3-kinase (PI3K)/AKT pathway activation in conferring resistance to trastuzumab and lapatinib. To address this question, we evaluated response to trastuzumab and lapatinib in a panel of 18 HER2-amplified cell lines, using both two- and three-dimensional culture. The SUM-225, HCC-1419, HCC-1954, UACC-893, HCC-1569, UACC-732, JIMT-1, and MDA-453 cell lines were found to be innately resistant to trastuzumab, whereas the MDA-361, MDA-453, HCC-1569, UACC-732, JIMT-1, HCC-202, and UACC-893 cells are innately lapatinib resistant. Lapatinib was active in de novo (SUM-225, HCC-1419, and HCC-1954) and in a BT-474 cell line with acquired resistance to trastuzumab. In these cells, trastuzumab had little effect on AKT phosphorylation, whereas lapatinib retained activity through the dephosphorylation of AKT. Increased phosphorylation of HER2, epidermal growth factor receptor, HER3, and insulin-like growth factor IR correlated with response to lapatinib but not trastuzumab. Loss of PTEN or the presence of activating mutations in PI3K marked resistance to trastuzumab, but lapatinib response was independent of these factors. Thus, increased activation of the PI3K/AKT pathway correlates with resistance to trastuzumab, which can be overcome by lapatinib. In conclusion, pharmacologic targeting of the PI3K/AKT pathway may provide benefit to HER2-positive breast cancer patients who are resistant to trastuzumab therapy. Mol Cancer Ther; 9(6); 1489–502. ©2010 AACR.
Going the distance: early results of a distributed medical education initiative for Royal College residencies in Canada.

BACKGROUND There is a shortage of specialty physicians practising in rural Canada: only 2.4% of Canadian specialist physicians practise rurally. Numerous strategies have been proposed and attempted that aim to increase the number of rural physicians. These include undergraduate and postgraduate distributed medical education opportunities. The Distributed Royal College Initiative at the University of Calgary is increasing the exposure of specialty residents to rural medicine through regional rotations and electives. An assessment of the initial impacts of this programme was made. METHODS Specialty residents were sent a voluntary survey following their regional rotation in academic year 2010-2011. The survey measured each resident's satisfaction with the experience, interest in undertaking another rotation and the impact of the rotation on potential rural practice location. The survey asked for written comments on the rotation. Data were analysed using descriptive statistics. RESULTS A total of 73% (29) of the 40 eligible residents completed the survey that was distributed upon completion of the rotation. In the survey, 45% of respondents indicated they would have been likely to practise in a regional community prior to the experience. This changed to 76% following the rotation. Analysis of the comments revealed strong positive characteristics of the experience across all disciplines. CONCLUSIONS Specialty-based, rural distributed programmes were perceived by the residents as educationally valuable and may be crucial in helping shift attitudes towards rural practice. Specific successful characteristics of the rotations provide direction to increase their quality further. These findings need to be verified in a larger sample.
Wavelet-Based Feature Extraction for the Analysis of EEG Signals Associated with Imagined Fists and Feet Movements

Electroencephalography (EEG) signals were analyzed in many research applications as a channel of communication between humans and computers. EEG signals associated with imagined fists and feet movements were filtered and processed using wavelet transform analysis for feature extraction. The proposed work used Neural Networks (NNs) as a classifier that enables the classification of imagined movements into either fists or feet. Wavelet families such as Daubechies, Symlets, and Coiflets wavelets were used to analyze the extracted events and then different feature extraction measures were calculated for three detail levels of the wavelet coefficients. Intensive NN training and testing experiments were carried out and different network configurations were compared. The optimum classification performance of 89.11% was achieved with a NN classifier of 20 hidden layers while using the Mean Absolute Value (MAV) of the Coiflets wavelet coefficients as inputs to NN. The proposed system showed a good performance that enables controlling computer applications via imagined fists and feet movements.
UVEITIS IN CHILDREN: ANALYSIS OF 274 CASES.

IN A PREVIOUS REPORT1 we described the findings in 47 cases of uveitis occurring in patients 16 years of age or younger out of 900 cases of uveitis surveyed in 1946-54. This preliminary report indicated that anterior uveitis in children is rare, and that chorioretinitis is relatively more common in this age group than anterior uveitis. Since 1954 we have studied 274 additional cases of uveitis and uveitis-like entities which occurred in patients 16 years of age or younger. Some of our previous concepts were confirmed, and others were not. The present study was made to provide information on the cause, course, and prognosis of an additional group of cases. Such a series of well-followed cases helps establish the natural course of the various childhood uveitis entities and provides information on the etiology and therapy.
Relationship between Serotypes, Age, and Clinical Presentation of Invasive Pneumococcal Disease in Madrid, Spain, after Introduction of the 7-Valent Pneumococcal Conjugate Vaccine into the Vaccination Calendar

ABSTRACT To assess invasive pneumococcal disease (IPD) clinical presentations and relationships with age and serotype in hospitalized children (<15 years) after PCV7 implementation in Madrid, Spain, a prospective 2-year (May 2007 to April 2009) laboratory-confirmed (culture and/or PCR) IPD surveillance study was performed (22 hospitals). All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids were sent to the reference laboratory for pneumolysin (ply) and autolysin (lyt) gene PCR analysis. A total of 330 IPDs were identified: 263 (79.7%) confirmed by culture and 67 (20.3%) confirmed by PCR. IPD distribution by age (months) was as follows: 23.6% (<12), 15.8% (12 to 23), 15.5% (24 to 35), 22.4% (36 to 59), and 22.7% (>59). Distribution by clinical presentation was as follows: 34.5% bacteremic pneumonia, 30.3% pediatric parapneumonic empyema (PPE), 13.6% meningitis, 13.3% primary bacteremia, and 8.2% others. Meningitis and primary bacteremia were the most frequent IPDs in children <12 months old, and bacteremic pneumonia and PPE were most frequent in those >36 months old. Frequencies of IPD-associated serotypes were as follows: 1, 26.1%; 19A, 18.8%; 5, 15.5%; 7F, 8.5%; 3, 3.9%; nontypeable/other 30 serotypes, 27.3%. Serotype 1 was linked to respiratory-associated IPD (38.6% in bacteremic pneumonia and 38.0% in PPE) and children of >36 months (51.4% for 36 to 59 months and 40.0% for >59 months), while serotype 19A was linked to nonrespiratory IPDs (31.1% in meningitis, 27.3% in primary bacteremia, and 51.9% in others) and children of <24 months (35.9% for children of <12 months and 36.5% for those 12 to 23 months old), with high nonsusceptibility rates for penicillin, cefotaxime, and erythromycin. After PCV7 implementation, non-PCV7 serotypes caused 95.5% of IPDs. The new 13-valent conjugate vaccine would provide 79.1% coverage of serotypes responsible for IPDs in this series.
Nematodirus battus infection in calves

In studies on the control of parasitic gastroenteritis in calves and sheep, involving an annual rotation of pastures grazed by these host species, it was shown that young cattle could play an important role in the epidemiology of Nematodirus battus, a species usually regarded as a parasite of lambs. Thus, young cattle readily acquired heavy burdens of N battus in spring and the contamination of pastures with eggs from these infections resulted in significant populations of larvae on the herbage, which were infective to both calves and lambs grazed on these pastures in the following year. Although the majority of the N battus eggs hatched in the spring, some hatched in the autumn. The calves developed a strong immunity to N battus during the grazing season as demonstrated by the absence of worms at necropsy in the autumn, despite the presence of infective larvae on the pasture.
Noncovalent Assembly of Anti-Dendritic Cell Antibodies and Antigens for Evoking Immune Responses In Vitro and In Vivo

Targeting of Ags directly to dendritic cells (DCs) through anti-DC receptor Ab fused to Ag proteins is a promising approach to vaccine development. However, not all Ags can be expressed as a rAb directly fused to a protein Ag. In this study, we show that noncovalent assembly of Ab–Ag complexes, mediated by interaction between dockerin and cohesin domains from cellulose-degrading bacteria, can greatly expand the range of Ags for this DC-targeting vaccine technology. rAbs with a dockerin domain fused to the rAb H chain C terminus are efficiently secreted by mammalian cells, and many Ags not secreted as rAb fusion proteins are readily expressed as cohesin directly fused to Ag either via secretion from mammalian cells or as soluble cytoplasmic Escherichia coli products. These form very stable and homogeneous complexes with rAb fused to dockerin. In vitro, these complexes can efficiently bind to human DC receptors followed by presentation to Ag-specific CD4+ and CD8+ T cells. Low doses of the HA1 subunit of influenza hemagglutinin conjugated through this means to anti-Langerin rAbs elicited Flu HA1-specific Ab and T cell responses in mice. Thus, the noncovalent assembly of rAb and Ag through dockerin and cohesin interaction provides a useful modular strategy for development and testing of prototype vaccines for elicitation of Ag-specific T and B cell responses, particularly when direct rAb fusions to Ag cannot be expressed.
Social, Health, and Age Differences Associated with Depressive Disorders in Women with Rheumatoid Arthritis

Depression in women with rheumatoid arthritis (RA) may be related to social role experiences, physical health, and age. The purpose of this study was to examine the social and health factors contributing to depression in two age groups of women with RA. One-hundred and thirty-eight midlife and late-life women with a diagnosis of RA participated in this cross sectional survey study. Multiple regression analysis indicated that social role balance, functional status, number of co-existing health problems, and age were significant predictors of depression in midlife and late-life women with RA. Role balance was the strongest factor contributing to a woman's depression score. Compared to midlife women, late-life women reported significantly higher role balance and lower depression scores, despite poorer functional status and more concomitant health problems.
Comparison of Sensory Modes of Biofeedback in Relaxation Training of Frontalis Muscle

The purpose of this study was to compare the effectiveness of various sensory modes of EMG biofeedback in relaxation training of the frontalis muscle. 19 male and 29 female subjects were randomly selected from a pool of college volunteers. They were then randomly assigned 12 each to audio-feedback, visual feedback, audiovisual feedback, and no feedback groups. There were 11 20-min. sessions per subject. Subjects in the biofeedback groups were trained to reduce muscle tension voluntarily by utilizing Cyborg J33 EMG portable trainers. The subjects in the three feedback groups exhibited significantly lower muscle tension than did the subjects in the no-feedback control group. There were no significant differences in relaxation among the three feedback groups.
Invasive mediastinal staging of non-small-cell lung cancer: a clinical practice guideline.

INTRODUCTION In non-small-cell lung cancer (nsclc), invasive mediastinal staging is typically used to guide treatment decision-making. Here, we present clinical practice guideline recommendations for invasive mediastinal staging in nsclc patients who have been staged T1-4, N0-3, with no distant metastases. METHODS Draft recommendations were formulated based on the best available evidence gathered by a systematic review and a consensus of expert opinion. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners through a survey assessing the clinical relevance and overall quality of the guideline. Feedback from the internal and external reviews was integrated into the clinical practice guideline. RESULTS In general, most clinical experts agreed with the guideline, approving it for methodologic rigour. More than 80% of the surveyed practitioners gave it a high quality rating. The expert reviewers also provided written comments, with some of the suggested changes being incorporated into the final version of the guideline. CONCLUSIONS In the clinical practice guideline, invasive mediastinal staging of nsclc is recommended in all cases except those involving patients with normal-sized lymph nodes, negative combine positron-emission tomography and computed tomography, and peripheral clinical stage 1A tumour. When performing mediastinoscopy, 5 nodal stations (2R/L, 4R/L, and 7) should routinely be examined.
Fire effects on soils: the human dimension

Soils are among the most valuable non-renewable resources on the Earth. They support natural vegetation and human agro-ecosystems, represent the largest terrestrial organic carbon stock, and act as stores and filters for water. Mankind has impacted on soils from its early days in many different ways, with burning being the first human perturbation at landscape scales. Fire has long been used as a tool to fertilize soils and control plant growth, but it can also substantially change vegetation, enhance soil erosion and even cause desertification of previously productive areas. Indeed fire is now regarded by some as the seventh soil-forming factor. Here we explore the effects of fire on soils as influenced by human interference. Human-induced fires have shaped our landscape for thousands of years and they are currently the most common fires in many parts of the world. We first give an overview of fire effect on soils and then focus specifically on (i) how traditional land-use practices involving fire, such as slash-and-burn or vegetation clearing, have affected and still are affecting soils; (ii) the effects of more modern uses of fire, such as fuel reduction or ecological burns, on soils; and (iii) the ongoing and potential future effects on soils of the complex interactions between human-induced land cover changes, climate warming and fire dynamics. This article is part of the themed issue ‘The interaction of fire and mankind’.
When do central banks prefer to intervene secretly

Central banks often intervene secretly in the foreign exchange market. This secrecy seems to be at odds with the signalling channel. In this article we will analyse when a central bank intervening in the foreign exchange rate market purely through the signalling channel would prefer to act secretly or publicly. By using a microstructure model, we will show that the consistency of the intervention with fundamentals, the volume of noise trading, the weight given to the effectiveness of intervention and the degree of superior information held by the central bank will influence the decision to intervene secretly or publicly. Copyright © 2008 John Wiley & Sons, Ltd.
Increasing availability of broadband access over copper network infrastructure

Currently dominant technology for the realization of broadband access over copper twisted pairs is Digital Subscriber Line (DSL) technology. Although the optical fiber provides significantly higher speeds than copper, it is anticipated that copper will remain in use for at least some time and will have in the coming years an important impact on further development and penetration of broadband services. A significant spread of copper access infrastructure and the application of DSL technology offers great opportunities for the provision of quality broadband services to a large number of end users, with a minimum required investment. Since complete replacement of the existing access infrastructure with optical fibers requires significant investment, it is still worth to invest in the development of equipment that uses copper infrastructure. Therefore it is imperative that DSL technology is optimized to improve its efficiency and ensure the required Quality of Service (QoS) for different types of multimedia services thus remaining competitive with other broadband access technologies.
Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.
Explaining the intention–behaviour gap in gluten-free diet adherence: The moderating roles of habit and perceived behavioural control

Adherence to a strict gluten-free diet is the only treatment for coeliac disease. Nonetheless, many individuals with the disease struggle to achieve and maintain strict adherence. While the theory of planned behaviour is useful for predicting gluten-free diet adherence, an intention–behaviour gap remains. The aim of this study was to investigate the roles of habit and perceived behavioural control in moderating the intention–behaviour relationship in gluten-free diet adherence. A significant three-way interaction was found such that the association between intention and adherence was dependent on both perceived behavioural control and habit. Implications for both theory and intervention design are discussed.
Nitrogen elimination from the tissues during oxygen breathing and its relationship to the fat:muscle ratio and the localization of bends

In a previous paper (Lundin, 1953) it has been shown that the nitrogen eliminated from the tissues during oxygen breathing seems to be released in an exponential way in three stages. First, there is a rapid phase with an elimination half-time of about 1-5 min, then a slower phase with a halftime of 12-13 min and lastly a slow phase with a half-time of about 110-200 min. On theoretical grounds it is probable that the first phase corresponds to the nitrogen from the highly vascular tissues, such as liver, brain, heart, intestines, etc., the middle phase to nitrogen mainly from the muscles, and the slowest to nitrogen mainly from fat. Probably the free intestinal nitrogen escapes with the third fraction. The values obtained above for the rapid and slow phases were very much the same as those obtained by Lawrence, Jones, Berg, Henry & Ivy (1948). However, the muscular phase had a higher elimination rate than that found in their experiments. Jones (1951) claims that the values ofLawrence et al. accord with the theory that the muscles give rise to the N2 bubbles appearing during decompression, which are the cause of the group of symptoms called decompression sickness. In the work of Lundin (1953) the tissue N2 elimination was determined from the accumulation of N2 during 02 breathing in a closed spirometer system. Because of technical difficulties involved in the collection and measurement of the small amount of N2 given off from the tissues during 02 breathing in a closed spirometer system, the importance of a further examination of this problem with another technique became evident. In the present study we have followed the elimination of N2 during 02 breathing by continuously measuring the changes in N2 concentration of end-tidal air.
A Hybrid State Estimator For Systems With Limited Number of PMUs

This paper is concerned about effective incorporation of a limited number of phasor measurement unit (PMU) measurements into the state estimation solution in order to enhance the state tracking accuracy and speed. This is particularly important for fast changing system conditions when rapid control action may be necessary based on the onset of voltage instability due to an unexpected event. Under such conditions, SCADA-based state estimators may be too slow in capturing the changes in system state due to the low scan rates of the order of seconds. PMU measurements on the other hand provide refresh rates of milliseconds; however, they may not provide full system observability. In this work, a solution is proposed in order to address the lack of observability by the PMU measurements while maintaining fast tracking capability as well as estimation robustness against pseudo-measurement and PMU errors. Robustness is accomplished via the use of the so-called least absolute value estimator which minimizes L1 norm of the residuals. Simulation results are provided to illustrate the expected benefits of this implementation on test systems.
Disruption of the keratin filament network during epithelial cell division.

The behaviour of keratin filaments during cell division was examined in a wide range of epithelial lines from several species. Almost half of them show keratin disruption as described previously: by immunofluorescence, filaments are replaced during mitosis by a ‘speckled’ pattern of discrete cytoplasmic dots. In the electron microscope these ‘speckles’ are seen as granules around the cell periphery, just below the actin cortical mesh, with no detectable 10 nm filament structure inside them and no keratin filament bundles in the rest of the cytoplasm. A time course of the filament reorganization was constructed from double immunofluorescence data; filaments are disrupted in prophase, and the filament network is intact again by cytokinesis. The phenomenon is restricted to cells rich in keratin filaments, such as keratinocytes; it is unrelated to the co‐existence of vimentin in many of these cells, and vimentin is generally maintained as filaments while the keratin is restructured. Some resistance to the effect may be conferred by an extended cycle time. Filament reorganization takes place within minutes, so that a reversible mechanism seems more likely than one involving de novo protein synthesis, at this metabolically quiet stage of the cell cycle.