Miracle-dz/UniFAR-FTUs huggingface dataset:
Men with breast cancer have better disease-specific survival than women.

HYPOTHESIS Male breast cancer patients have better disease-specific survival than carefully matched female breast cancer patients. DESIGN Retrospective study. SETTING University hospital. PATIENTS AND METHODS Each man in the breast cancer database at Columbia-Presbyterian Medical Center (New York, NY) between the years 1980 and 1998 was matched with a woman. Matching was done based on age and date of diagnosis, stage, and primary histologic findings. MAIN OUTCOME MEASURES The overall survivals and disease-specific survivals of the male breast cancer group and female breast cancer group were compared. RESULTS Fifty-three male patients were matched with an equal number of female breast cancer patients. The Kaplan-Meier curves demonstrated that there was no significant difference in overall survival. The 5- and 10-year survivals for women were 0.77 and 0.51, and for men 0.77 and 0.56. When the Kaplan-Meier curves for breast cancer-specific survival were compared, however, there was a significant difference in the 5- and 10-year survivals (P = .05, log-rank test). For women, the 5- and 10-year disease-specific survival was 0.81 and 0.7, respectively, while for men it was 0.9 and 0.9, respectively. In a Cox regression analysis for time to death from breast cancer, stage was the only predictor of death that approached significance (P = .06). CONCLUSIONS While the overall survivals were equivalent, male breast cancer patients had significantly better disease-specific survivals compared with their female counterparts. Male patients were 4 times more likely to die of other causes than their breast cancer.
Transformation of in vitro tools for kinase profiling: keeping an eye over the off-target liabilities

Introduction: Over the past decade, there has been an increased number of FDA approved small molecule kinase inhibitors for the treatment of cancer. This is due, in part, to an increased understanding of the fundamental aspects of kinase biology, coupled with advances in the methods used to study the inhibitory effects of small molecules on kinase activity. Underlying the development of these inhibitors are profiling methods that are used to assess the effect of potential compounds against their desired and undesired targets. The advancement of kinase profiling has stemmed from the development of basic assay technology that allows compounds to be tested against ever larger panels of kinases in a robust, cost-effective manner. Methods have also been developed that rapidly assess compound activity against specific activation states of kinases. There has also been a development of newer methods that move beyond traditional biochemical formats, which take a ‘whole cell’ approach to compound profiling. Areas Covered: This review provides an overview of traditional biochemical-based kinase profiling as well as an introduction to advances that have been made by moving compound profiling into a cell-based format. Expert opinion: While central to the appropriate prioritization and optimization of compounds during the hit to lead phase of early-stage pharmaceutical development, every compound profiling format must be critically assessed so that one can make informed decisions through an understanding of their strengths and limitations. These decisions will ultimately be balanced against cost, complexity and its biological relevance.
Developing a User Oriented Design Methodology for Learning Activities Using Boundary Objects.

International Standards in High and Open and Distance Education are used for developing Open Educational Resources (OERs). Current issues in e-learning community are the specification of learning chunks and the definition of describing designs for different units of learning (activities, units, courses) in a generic though expandable format. Developing educational content, courseware and pedagogical tools to support Subject Matter Experts in their educational practice is a challenging task for the Instructional Design Field. This paper’s aim is to introduce a user oriented design methodology for Open and Distance Learning (ODL) activities orchestrating pedagogical tools so as to develop e-learning activities in Hellenic Open University (HOU) by the use of Boundary Objects (BOs).
Effects of Combined Electromyostimulation and Gymnastics Training in Prepubertal Girls

Deley, G, Cometti, C, Fatnassi, A, Paizis, C, and Babault, N. Effects of combined electromyostimulation and gymnastics training in prepubertal girls. J Strength Cond Res 25(2): 520-526, 2011-This study investigated the effects of a 6-week combined electromyostimulation (EMS) and gymnastic training program on muscle strength and vertical jump performance of prepubertal gymnasts. Sixteen young women gymnasts (age 12.4 ± 1.2 yrs) participated in this study, with 8 in the EMS group and the remaining 8 as controls. EMS was conducted on knee extensor muscles for 20 minutes 3 times a week during the first 3 weeks and once a week during the last 3 weeks. Gymnasts from both groups underwent similar gymnastics training 5-6 times a week. Isokinetic torque of the knee extensors was determined at different eccentric and concentric angular velocities ranging from −60 to +240° per second. Jumping ability was evaluated using squat jump (SJ), counter movement jump (CMJ), reactivity test, and 3 gymnastic-specific jumps. After the first 3 weeks of EMS, maximal voluntary torque was increased (+40.0 ± 10.0%, +35.3 ± 11.8%, and +50.6 ± 7.7% for −60, +60, and +240°s−1, respectively; p < 0.05), as well as SJ, reactivity test and specific jump performances (+20.9 ± 8.3%, +20.4 ± 26.2% and +14.9 ± 17.2% respectively; p < 0.05). Six weeks of EMS were necessary to improve the CMJ (+10.1 ± 10.0%, p < 0.05). Improvements in jump ability were still maintained 1 month after the end of the EMS training program. To conclude, these results first demonstrate that in prepubertal gymnasts, a 6-week EMS program, combined with the daily gymnastic training, induced significant increases both in knee extensor muscle strength and nonspecific and some specific jump performances.
Chromosome instability associated with human alphoid DNA transfected into the Chinese hamster genome

Repetitive DNA sequences have been implicated in the mediation of DNA rearrangement in mammalian cells. We have tested this hypothesis by using a dihydrofolate reductase (DHFR) expression vector into which candidate sequences were inserted. DHFR- Chinese hamster ovary (CHO) cells were transfected with this vector, the amplification of which was then selected for by methotrexate (MTX) exposure. Cells transfected with the vector alone (and resistant to 0.02 or 1.0 microM MTX) or with a poly(dG-dT) insert (and resistant to 0.05 or 1.0 microM MTX) showed little change in chromosome aberrations or sister chromatid exchange frequencies. In contrast, transfection of DHFR- CHO cells with a vector containing either of two distinct 0.34-kilobase human alphoid DNA segments (and selection to 0.05 to 10.0 microM MTX) showed an approximately 50% increase in chromosome number and marked changes in chromosome structure, including one or two dicentric or ring forms per cell. The sister chromatid exchange frequency also increased, to more than double the frequency of that in cells transfected without insert or those containing poly(dG-dT). In situ hybridization of one 0.34-kilobase insert in some cells suggested clustering of homologous sequences in structurally abnormal recipient CHO cell chromosomes. The approach described provides an introduction to a unique means for a coordinate molecular and cytological study of dynamic changes in chromosome structure.
The renal cortical collecting duct: a secreting epithelium?

The cortical collecting duct (CCD) plays an essential role in sodium homeostasis by fine‐tuning the amount of sodium that is excreted in the urine. Ex vivo, the microperfused CCD reabsorbs sodium in the absence of lumen‐to‐bath concentration gradients. In the present study, we show that, in the presence of physiological lumen‐to‐bath concentration gradients, and in the absence of endocrine, paracrine and neural regulation, the mouse CCD secretes sodium, which represents a paradigm shift. This secretion occurs via the paracellular route, as well as a transcellular pathway that is energized by apical H+/K+‐ATPase type 2 pumps operating as Na+/K+ exchangers. The newly identified transcellular secretory pathway represents a physiological target for the regulation of sodium handling and for anti‐hypertensive therapeutic agents.
Investigation of Vehicle-to-Infrastructure Communications based on IPv6-Based Automotive Telematics

Automotive telematics is expected to be prevalent due to both market pull and technology push driving forces. By considering ITS networking needs, auto-telematics should provide mobile Internet services for fulfill these needs, and IPv6-based auto-telematics might effectively achieve IP ubiquity and network mobility, which are key technologies for mobile Internet. In this study, an IPv6-based automotive telematics is developed to investigate IPv6 networking systems for ITS. The prototype is made for field trials and performance evaluation purposes.
Comparison of agomelatine and selective serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors in major depressive disorder: A meta-analysis of head-to-head randomized clinical trials

Objective: Agomelatine is a new antidepressant with unique melatonin receptor type 1A (MTNR1A) and 1B ( MTNR1B) agonism and serotonergic receptor 5-hydroxytryptamine receptor 2C (5-HT-2C) antagonism. Several studies of patients with major depressive disorder (MDD) have confirmed the superior efficacy and safety of agomelatine in comparison with established treatments, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). This meta-analysis comprehensively shows the efficacy, acceptability, and safety of agomelatine in comparison with SSRIs and SNRIs used as antidepressants in MDD. Method: Comprehensive electronic database searches were performed to identify reports of head-to-head randomized controlled trials that have compared agomelatine with SSRIs or SNRIs in terms of efficacy/effectiveness in treating MDD. Response and remission rates at both acute (6–12 weeks) and follow-up (24 weeks) phases, Clinical Global Impression-Improvement Scale response and remission rates, changes in depression scale scores, improvements in subjective sleep, dropout rates, and side effect rates were extracted and analysed. Results: The meta-analysis included six head-to-head trials involving 1871 patients. In the acute phase, agomelatine had higher response rates (relative risk (RR) 1.08, 95% confidence interval (CI) 1.02–1.15) compared to SSRIs and SNRIs. In the remission analysis, only acute remission rates (RR 1.12, 95% CI 1.01–1.24) significantly differed. The action of agomelatine was superior on the Leeds Sleep Evaluation Questionnaire-Quality of Sleep score (mean difference 4.05, 95% CI 0.61–7.49). Discontinuation due to inefficacy did not differ between agomelatine and SSRIs/SNRIs (RR 0.74, 95% CI 0.42–1.28). Compared to SSRIs and SNRIs, however, agomelatine revealed a lower rate of discontinuation due to side effects (RR 0.38, 95% CI 0.25–0.57). Conclusions: Agomelatine has significantly higher efficacy and potential acceptability compared to SSRIs and SNRIs when treating MDD. However, the difference in efficacy is not considered clinically relevant. Because of its unique chronobiotic effects, agomelatine may be useful for the management of some MDD patients with circadian disturbance.
DNA Microarray-Based Identification of Genes Regulated by NtrC in Bradyrhizobium japonicum

ABSTRACT The Bradyrhizobium japonicum NtrBC two-component system is a critical regulator of cellular nitrogen metabolism, including the acquisition and catabolism of nitrogenous compounds. To better define the roles of this system, genome-wide transcriptional profiling was performed to identify the NtrC regulon during the response to nitrogen limitation. Upon cells perceiving low intracellular nitrogen, they stimulate the phosphorylation of NtrC, which induces genes responsible for alteration of the core glutamine synthetase/glutamate synthase nitrogen assimilation pathway, including the genes for the glutamine synthetases and PII proteins. In addition, genes responsible for the import and utilization of multiple nitrogen sources, specifically nitrate and nitrite, were upregulated by NtrC activation. Mutational analysis of a candidate nitrite reductase revealed a role for NtrC in regulating the assimilation of nitrite, since mutations in both ntrC and the gene encoding the candidate nitrite reductase abolished the ability to grow on nitrite as a sole nitrogen source.
Citizens’ perceptions of government’s participatory use of social media

Purpose This paper aims to investigate the perceptions of Omani citizens toward the use of social media by the government for participatory and interactive relationships. More precisely, the descriptive nature of the study resides in its ability to explain how social media users regard the current status and levels of presence, transparency, engagement, responsiveness and trust about the current use of social media by the Omani Government. Design/methodology/approach A quantitative approach was used to collect data. This was done via a self-administered questionnaire from a return sample of 1,769 citizens drawn from different places in Oman. These citizens were considered as well-informed and regular active users of social media. The reviewed literature provided a basis for the construct of the questionnaire. Findings The overall results indicated modest levels of agreement in all of the investigated factors. The neutral findings suggest that there is a level of uncertainty among the respondents regarding how the government is determining the potential of social media for participatory and interactive relationships. Findings in this study advocate the outcomes of the recent Arab Social Media Report, plus the few relevant studies included in the literature, which nearly stated that although there is a growing use of social media among citizens, governments are failing to take full advantage of social media. Governments are also failing to engage citizens to design and deliver more efficient and collaborative services, per this study’s findings. Practical/implications The findings call for the importance of strategically framing the use of participatory social media by the government. In a broader sense, the findings of this study are beneficial to all contexts that share similar political and socio-economic philosophy, especially the Arab states and most of the developing countries. The findings provide insights for governments in need of developing social media strategies to promote more collaborative and interactive governance. Originality/value The study aids in understanding the views of citizens who are the current major players in a highly technology-driven environment. This environment is found to be transforming the relationship between citizens and governments. The study adds knowledge to the currently scarce body of literature dealing with issues pertaining to citizen–government relationships in social media in the Arab states, and similar contexts in developing countries. Its findings may provide valuable insights for policy makers to leverage collaborative relationships between governments and citizens.
Role for Microphthalmia Transcription Factor in the Diagnosis of Metastatic Malignant Melanoma

Microphthalmia transcription factor (Mitf), a protein critical for the embryonic development and postnatal viability of melanocytes, is a master lineage regulator and modulates extracellular signals. Recently, an anti-Mitf antibody, D5, was shown to be both a sensitive and a specific marker of epithelioid melanoma (1). Those data suggested that Mitf expression was specific for melanocytic differentiation because it was not detected in six different carcinoma types. To broaden the spectrum of melanomatous and nonmelanomatous tumors tested with this antibody, the authors investigated the sensitivity and specificity of the D5 anti-Mitf antibody in 36 metastatic melanomas and 102 nonmelanomatous tumors. Twenty-nine of 36 (81%) melanomas examined were reactive for D5. Of these, 29 of 32 (91%) epithelioid melanomas were reactive, whereas all 4 melanomas with spindle cell morphology were nonreactive. Six of 102 (5.8%) nonmelanomatous tumors (1 breast carcinoma, 1 malignant mixed mullerian tumor, 2 renal cell carcinomas, and 2 leiomyosarcomas) were reactive for D5. All melanomas were reactive for S-100 protein (a criteria for inclusion in the study), whereas 8 of 102 (7.8%) of nonmelanomatous tumors were reactive. Twenty-five of 36 melanomas (69%) were reactive for HMB-45, whereas no nonmelanomatous tumors were reactive. Twenty-one of 28 (75%) melanomas were reactive for Melan-A. Reactivity for Melan-A was detected in 5 of 102 (4.9%) nonmelanomatous tumors. As with D5, HMB-45 and Melan-A failed to detect all spindle-cell melanomas. Results of this study confirm that D5 is a sensitive marker for epithelioid melanomas; however, the authors found D5 neither quite as sensitive nor quite as specific as in previous studies. Nevertheless, the authors believe that positive staining for D5 when taken in clinical, histologic, and immunohistochemical context may be diagnostically useful. In particular, D5 is helpful in the evaluation of epithelioid neoplasms, but not spindle-cell tumors.
An Inherited Metabolic Disorder Presenting as Ethylene Glycol Intoxication in a Young Adult

Despite the abundance of reports emerging in the literature on metabolic disorders, some disorders remain undiagnosed or misdiagnosed, not only in clinical pathology but also in forensic pathology. The authors report a patient who had recurrent episodes characterized by nausea, vomiting, and signs of dehydration necessitating admission to the hospital. At each admission, he was found to have lactic acidosis. On the first admission, glycolic acid was detected in his blood and he was diagnosed as having ethylene glycol intoxication. Only at the third admission, 2 years after the first, was the possibility of an underlying metabolic disorder considered. Laboratory investigations showed a deficiency of complex I in the mitochondrial oxidative phosphorylation. Possible medicolegal implications are discussed.
Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal  Structures

The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Cor-ticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the trans-membrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hex-agonal setting with translational non-crystallographic symmetry. Molecular dynamics and metadynamics simulations on this novel structure and the existing TMD structure for CRF1R provides insight as to how the small molecule ligand gains access to the induced-fit allosteric binding site with implications for the observed selectivity against CRF2R. Furthermore, molecular dynamics simulations performed using a full-length receptor model point to key interactions between the ECD and extracellular loop 3 of the TMD providing insight into the full inactive state of multidomain class B GPCRs.
Relative Movements of Domains in Large Molecules of the Immune System

Molecular dynamics was used to simulate large molecules of the immune system (major histocompatibility complex class I, presented epitope, T-cell receptor, and a CD8 coreceptor.) To characterize the relative orientation and movements of domains local coordinate systems (based on principal component analysis) were generated and directional cosines and Euler angles were computed. As a most interesting result, we found that the presence of the coreceptor seems to influence the dynamics within the protein complex, in particular the relative movements of the two α-helices, Gα 1 and Gα 2.
Differential CD4/CCR5 Utilization, gp120 Conformation, and Neutralization Sensitivity between Envelopes from a Microglia-Adapted Human Immunodeficiency Virus Type 1 and Its Parental Isolate

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infects and induces syncytium formation in microglial cells from the central nervous system (CNS). A primary isolate (HIV-1BORI) was sequentially passaged in cultured microglia, and the isolate recovered (HIV-1BORI-15) showed high levels of fusion and replicated more efficiently in microglia (J. M. Strizki, A. V. Albright, H. Sheng, M. O'Connor, L. Perrin, and F. González-Scarano, J. Virol. 70:7654–7662, 1996). The parent and adapted viruses used CCR5 as coreceptor. Recombinant viruses demonstrated that the syncytium-inducing phenotype was associated with four amino acid differences in the V1/V2 region of the viral gp120 (J. T. C. Shieh, J. Martin, G. Baltuch, M. H. Malim, and F. González-Scarano, J. Virol. 74:693–701, 2000). We produced luciferase-reporter, env-pseudotyped viruses using plasmids containing env sequences from HIV-1BORI, HIV-1BORI-15, and the V1/V2 region of HIV-1BORI-15 in the context of HIV-1BORI env (named rBORI, rB15, and rV1V2, respectively). The pseudotypes were used to infect cells expressing various amounts of CD4 and CCR5 on the surface. In contrast to the parent recombinant, the rB15 and rV1V2 pseudotypes retained their infectability in cells expressing low levels of CD4 independent of the levels of CCR5, and they infected cells expressing CD4 with a chimeric coreceptor containing the third extracellular loop of CCR2b in the context of CCR5 or a CCR5 Δ4 amino-terminal deletion mutant. The VH-rB15 and VH-rV1V2 recombinant viruses were more sensitive to neutralization by a panel of HIV-positive sera than was VH-rBORI. Interestingly, the CD4-induced 17b epitope on gp120 was more accessible in the rB15 and rV1V2 pseudotypes than in rBORI, even before CD4 binding, and concomitantly, the rB15 and rV1V2 pseudotypes were more sensitive to neutralization with the human 17b monoclonal antibody. Adaptation to growth in microglia—cells that have reduced expression of CD4 in comparison with other cell types—appears to be associated with changes in gp120 that modify its ability to utilize CD4 and CCR5. Changes in the availability of the 17b epitope indicate that these affect conformation. These results imply that the process of adaptation to certain tissue types such as the CNS directly affects the interaction of HIV-1 envelope glycoproteins with cell surface components and with humoral immune responses.
Do Islamic HRM Practices Influence Employee Outcomes: Mediating Role of Employee Engagement

Islam is a complete code of life and it motivates all Muslims to perform their duties effectively. It guides at every step of life. Similarly, it also explains teachings about managing people in an organization. The aim of this study is to explore the effects of Islamic human resource management (HRM) on employees’ outcomes under mediation by employee engagement in Islamic banks in Pakistan. This is quantitative study and data collected by using personal administered questionnaires. The 170 questionnaires were floated among employees of Islamic banks in Pakistan. The questionnaire included validated scales of Islamic HRM, employee engagement, job satisfaction, turnover intentions and organizational commitment. The results revealed that selected banks consider Islamic approach during HRM functions. The results of regression and correlation analyses indicate that Islamic HRM is significantly and highly correlated to employee outcomes. The multiple regression analysis revealed that employee engagement mediated the relationship between Islamic HRM and employee outcomes.