Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combined Strategy of SAGE and Quantitative PCR Provides a 13-Gene Signature that Predicts Preoperative Chemoradiotherapy Response and Outcome in Rectal Cancer

Purpose: Preoperative chemoradiotherapy (CRT) is the treatment of choice for rectal cancer (RC), but half of the patients do not respond, suffer unnecessary toxicities, and surgery delays. We aimed to develop a model that could predict a clinically meaningful response to CRT by using formalin-fixed paraffin-embedded (FFPE) biopsies. Experimental Design: We first carried out an exploratory screening of candidate genes by using SAGE technology to evaluate dynamic changes in the RC transcriptome in selected refractory patients before and after CRT. Next, 53 genes (24 from SAGE and 29 from the literature) were analyzed by qPCR arrays in FFPE initial biopsies from 94 stage II/III RC patients who were preoperatively treated with CRT. Tumor response was defined by using Dworak's tumor regression grade (2–3–4 vs. 0–1). Multivariate Cox methods and stepwise algorithms were applied to generate an optimized predictor of response and outcome. Results: In the training cohort (57 patients), a 13-gene signature predicted tumor response with 86% accuracy, 87% sensitivity, and 82% specificity. In a testing cohort (37 patients), the model correctly classified 6 of 7 nonresponders, with an overall accuracy of 76%. A signature-based score identified patients with a higher risk of relapse in univariate (3-year disease-free survival 64% vs. 90%, P = 0.001) and multivariate analysis (HR = 4.35 95% CI: 1.2–15.75, P = 0.02), in which it remained the only statistically significant prognostic factor. Conclusions: A basal 13-gene signature efficiently predicted CRT response and outcome. Multicentric validation by the GEMCAD collaborative group is currently ongoing. If confirmed, the predictor could be used to improve patient selection in RC studies. Clin Cancer Res; 17(12); 4145–54. ©2011 AACR.
METABOLISM OF MELATONIN BY HUMAN CYTOCHROMES P450

In humans, the pineal hormone melatonin (MEL) is principally metabolized to 6-hydroxymelatonin (6-HMEL), which is further conjugated with sulfate and excreted in urine. MEL O-demethylation represents a minor reaction. The exact role of individual human cytochromes P450 (P450s) in these pathways has not been established. We used a panel of 11 recombinant human P450 isozymes to investigate for the first time the 6-hydroxylation and O-demethylation of MEL. CYP1A1, CYP1A2, and CYP1B1 all 6-hydroxylated MEL, with CYP2C19 playing a minor role. These reactions were NADPH-dependent. CYP2C19 and, to some extent CYP1A2, O-demethylated MEL. The Km (μM) and Vmax (kcat, pmol min-1 pmol-1 P450) for 6-hydroxylation were estimated as 19.2 ± 2.01 and 6.46 ± 0.22 (CYP1A1), 25.9 ± 2.47 and 10.6 ± 0.32 (CYP1A2), and 30.9 ± 3.76 and 5.31 ± 0.21 (CYP1B1). These findings confirm the suggestion of others that CYP1A2 is probably the foremost hepatic P450 in the 6-hydroxylation of MEL and a single report that CYP1A1 is also able to mediate this reaction. However, this is the first time that CYP1B1 has been shown to 6-hydroxylate MEL. The IC50 for the CYP1B1-selective inhibitor (E)-2,4,3′,5′-tetramethoxystilbene was estimated to be 30 nM for MEL 6-hydroxylation by recombinant human CYP1B1. Comparison of brain homogenates from wild-type and cyp1b1-null mice revealed that MEL 6-hydroxylation was clearly mediated to a significant degree by CYP1B1. CYP1B1 is not expressed in the liver but has a ubiquitous extrahepatic distribution, and is found at high levels in tissues that also accumulate either MEL or 6-HMEL, such as intestine and cerebral cortex, where it may assist in regulating levels of MEL and 6-HMEL.
Brain complexity born out of criticality

In this essay we elaborate on recent evidence demonstrating the presence of a second order phase transition in human brain dynamics and discuss its consequences for theoretical approaches to brain function. We review early evidence of criticality in brain dynamics at different spatial and temporal scales, and we stress how it was necessary to unify concepts and analysis techniques across scales to introduce the adequate order and control parameters which define the transition. A discussion on the relation between structural vs. dynamical complexity exposes future steps to understand the dynamics of the connectome (structure) from which emerges the cognitome (function).
Comparison of developmental status of 5-year-old singleton children born through assisted and natural conceptions

Background: Approximately one percent of current live births of the world are conceived via assisted reproductive technologies (ART). Objective: The purpose of this study was to compare the developmental status of children born through assisted and natural conceptions at the age of five years. Materials and Methods: In a retrospective cohort study, developmental status of 5 years old children was evaluated via Persian version of 60-month Ages and Stages Questionnaires. Case group consisted of 61 singletons, term babies whom were born through ART in the Research and Clinical Center for Infertility, Yazd, Iran in 2005. Control group consisted of 61 term, first child, singleton and spontaneously conceived born five years old children whom were referred to Shahid Akbari primary health care center in 2010. Results: 58 girls (47.5%) and 64 boys (52.5%) were evaluated. Frequency of developmental delay in domains of fine motor (47.5% vs. 24.6%, p=0.008) and problem solving (60.6% vs. 34.4%, p=0.004) were more in ART born children. On logistic regression, fine motor development state was independently affected by maternal educational level (OR: 5.3, 95% CI: 1.67-16.30, p=0.004) and developmental status in problem solving domains was independently affected by maternal educational level (OR: 4.88, 95% CI: 1.25-19.07, p=0.02) and birth weight (OR: 7.1, 95% CI: 1.78-29.01, p=0.006) Conclusion: Maternal educational level and birth weight are important factors that influenced developmental outcome of ART born children.
Expression of Activity-Dependent Neuroprotective Protein in the Immune System: Possible Functions and Relevance to Multiple Sclerosis

Background: Activity-dependent neuroprotector (ADNP) is a neuroprotective molecule containing an 8-amino acid peptide, NAPVSIPQ (NAP), that is sufficient for its neuroprotective effects. Objective: To assess the expression of ADNP in the human immune system in normal subjects and multiple sclerosis patients. MaterialsandMethods: ADNP expression was assessed in peripheral blood mononuclear cells (PBMCs) from healthy donors and multiple sclerosis (MS) patients using staining with anti-ADNP (NAP) antibodies and markers for T cells, B cells, monocytes and natural killer cells. ADNP mRNA was determined in peripheral blood from MS patients (n = 24) and matched controls (n = 21). Expression of activation markers CD69 and CD154 and of IFN-γ was assessed by flow cytometry in stimulated PBMCs. Effects of NAP on immune cell proliferation was assessed by tritiated thymidine incorporation. Results: Monocytes, B cells and T cells, but not regulatory (CD4+CD25+) T cells expressed ADNP. NAP peptide decreased the expression of CD69, CD154 and IFN-γ in PBMC and caused suppressed anti-CD3-/anti-CD28-stimulated PBMC proliferation. ADNP mRNA was reduced in MS compared to control peripheral blood. Conclusion: ADNP is expressed in many immune system cells. ADNP mRNA is reduced in PBMCs in MS. The peptide NAP, which plays an important role in neuroprotection, has potential immunomodulatory properties.
Judging credibility: Can spaced lessons help students think more critically online?

wileyonlinelibrary.com/journal/acp 1032 Summary Despite the prevalence of the spacing effect in the psychological literature, the impact of lesson timing has not yet been fully explored in real classrooms. The current study examined whether spacing could improve long‐term retention of both factual and critical thinking curriculum‐based teaching materials for children. Students 9 to 12 years old were taught to judge the credibility of websites in either three consecutive days of lessons or one lesson per week. Thirty‐five days after the final lesson, students were tested on factual knowledge and applied their knowledge to evaluating a new website. Students in the spaced condition remembered more facts from the lessons and were better able to explain their website ratings than students in the massed group.
“My Family Are Supportive . . . But People in My Village Mock Me”: Bonding and Bridging Capital among Women Pursuing Secondary Education in Kathmandu, Nepal

Women’s secondary schools have become an option for educational attainment in Nepal. We assess bonding and bridging social capital available to women who attend the Utprerana Women Secondary School (UWSS) in Nepal’s major city of Kathmandu. Using qualitative approaches, we consider the social capital available to women that both encourages and limits women’s educational access and address the networks women build when attending school. Bonding capital both encourages women to pursue their education and demands that women conform to traditional roles. School attendance prompts a change in bonding social capital, accumulated with family prior to school attendance. Women add to their bonding social capital by strengthening relationships with classmates and teachers. Women’s school attendance improved bridging social capital by enhancing future opportunities. Bonding social capital formed within the school provides emotional support, personal space from domestic responsibilities, and a sense of freedom, while demanding women’s conformity to expectations for student conduct.
The Primordial Helium Abundance

I present a brief review on the determination of the primordial helium abundance by unit mass, Yp. I discuss the importance of the primordial helium abundance in: (a) cosmology, (b) testing the standard big bang nucleosynthesis, (c) studying the physical conditions in H II regions, (d) providing the initial conditions for stellar evolution models, and (e) testing the galactic chemical evolution models.
The comparison of flow experience in retiree’s serious and casual leisure participation

ABSTRACT The study focussed on investigating how retirees reach the flow experience and also discussed how the serious and casual leisure activities influence the flow experience. The participants included twenty retirees, and data collection was completed using Experience Sampling Form (ESF). These forms were filled in by the participants at a fixed time each day for one week. The results showed that the occurrence rate of flow experience is significantly affected by engagement in serious leisure activities, rather than casual leisure activities.
The effect of ship shape and anemometer location on wind speed measurements obtained from ships

Wind speed measurements obtained from ship-mounted anemometers are biased by the distortion of the airflow around the ship's hull and superstructure. These wind speed measurements are used both in numerical weather prediction and in climate studies and need to be known as accurately as possible. This paper presents results from threedimensional CFD studies of the mean airflow over various research ships and a generic tanker/bulk. It will be shown that the bias in the wind speed measurements is highly dependent upon anemometer position and ship shape. CFD results are compared to in situ wind speed measurementsmade from a number of anemometers above the bridge of the RRS Charles Darwin.
Spatial Choice: A Matter of Utility or Regret?

This paper provides an empirical comparison between utility-maximization and regret-minimization perspectives of spatial-choice behaviour. The key difference between these two perspectives is that the regret-minimization perspective implies that the anticipated satisfaction associated with a chosen spatial alternative depends on the anticipated performance of nonchosen alternatives. In order to provide a meaningful statistical comparison, we formulate a model of regret minimization such that it reduces to utility maximization for a given parameter restriction. Estimation results, based on a binary stated travel-mode-choice experiment, show how the regret-based model outperforms its utilitarian counterpart. Furthermore it is shown how participants in the experiment attached relatively much weight to the situation where the nonchosen alternative is slightly better than the chosen one, and they tend to discount larger differences. We show how this concavity of the regret function is in line with the prospect theoretical notion of risk-seeking behaviour in the domain of losses.
XMM-Newton study of the lensing cluster of galaxies CL 0024+17

We present a detailed gravitational mass measurement based on the XMM-Newton imaging spectroscopy analysis of the lensing cluster of galaxies CL 0024+17 at z = 0.395. The emission appears approximately symmetric. However, on the scale of r ∼ 3.3 � some indication of elongation is visible in the northwest-southeast (NW-SE) direction from the hardness ratio map (HRM). Within 3 � , we measure a global gas temperature of 3.52 ± 0.17 keV, metallicity of 0.22 ± 0.07, and bolometric luminosity of 2.9 ± 0.1 × 10 44 h −2 70 erg s −1 . We derive a temperature distribution with an isothermal temperature of 3.9 keV to a radius of 1.5 � and a temperature gradient in the outskirts (1.3 � < r < 3 � ). Under the assumption of hydrostatic equilibrium, we measure gravitational mass and gas mass fraction to be M200 = 2.0 ± 0.3 × 10 14 h −1 70 Mand fgas = 0.20 ± 0.03 h −3/2 70 at r200 = 1.05 h −1 70 Mpc using the observed temperature profile. The complex structure in the core region is the key to explaining the discrepancy in gravitational mass determined from XMM-Newton X-ray observations and HST optical lensing measurements.
How Do Coworkers “Make the Place”? Examining Coworker Conflict and the Value of Harmony in China and the United States

The goal of this study was to test cross-cultural/cross-national differences in the association between coworker interpersonal justice and coworker conflict and the implications of such differences for employee effectiveness. Harmony is a central value in China but is less important in the United States, and the individual value of harmony may influence Chinese and US employees differently in their response to low levels of coworker interpersonal justice. We collected data from employees and their coworkers in China (214 dyads) and the US (301 dyads). There were three major findings. First, coworker interpersonal justice was negatively related to coworker conflict. Second, coworker conflict significantly mediated coworker interpersonal justice in relation to the employee effectiveness variables of task performance, organisational citizenship behaviours, and counterproductive work behaviours. Finally, in the Chinese sample, harmony significantly buffered the indirect effect of coworker interpersonal justice on employee effectiveness via coworker conflict, whereas in the US sample, harmony significantly intensified the indirect effect of coworker interpersonal justice on employee effectiveness via coworker conflict.
On the inevitable intertwining of analysis and design: developing systems for complex cooperations

Developing interactive software systems requires the well known tasks of analysis, design and construction. In the context of work settings with complex cooperations these tasks and their relationsship undergo drastic changes. Analysis and design have to be accomplished at different levels of complexity, the heterogeneity of users envolved needs to be handled and the presentation of anticipated changes incorporating the organizational context goes beyond proven (object-oriented) techniques like prototyping. The article claims that complex cooperations require a close intertwining of analysis and design. It is accomplishable by application-driven documents usable in different stages of the development process. Based on a document-driven evolutionaly approach examples of such document types like Cooperation Pictures and Purpose Tables - are given. They are discussed based on expericences from projects in different application domains.
Wireless Authentication Protocol Preserving User Anonymity

We propose an authentication and key agreement protocol while preserving the anonymity of a mobile user in wireless mobile environments. When a mobile user and his visited network mu-tually authenticate each other, the anonymity of the user should be preserved. In order to provide user anonymity, we introduce new method of computing the temporary identity (TID) during the authentication process. TID is initially computed by a user at the beginning and updated by both user and network side during the execution of the protocol. In addition to guarantee-ing user anonymity, we also consider the secure key agreement at the same time.
Individual vs General Time-Motion Analysis and Physiological Response in 4 vs 4 and 5 vs 5 Small-Sided Soccer Games

The purposes of this study were to present a new time-motion analysis approach in soccer small-sided games by incorporating the physical potential of individual players and to evaluate the physiological response applied to 4 vs. 4 and 5 vs. 5 small-sided games. Thirteen professional soccer players participated in small-sided game training sessions. The physical demands (GPS) and physiological responses (Heart Rate – HR) of the 4 vs. 4 and 5 vs. 5 small-sided games were compared. In contrast to previous studies, speed zones were divided individually for each player according to his maximal running speed (Smax) and running velocity at the lactate threshold (V/LT). The analyses confirmed that the mean V/LT of the player was 3.8 ± 0.16 m·s-1 and the Smax speed was 8.26 ± 0.65 m·s-1. The total distance covered during the 4 vs. 4 games was significantly longer than that covered during the 5 vs. 5 games. The application of obligatory limits for speed zones could result in an inappropriate assessment of the players’ commitment during training. Utilizing an individual assessment of player motion during small-sided games can improve the optimization of training load application.
Experimental platform for Wizard-of-Oz evaluations of biomimetic active vision in robots

A novel paradigm for the evaluation of humanrobot interaction is proposed, with special focus on the importance of natural eye and head movements in nonverbal human-machine communication scenarios. We present an experimental platform that will enable Wizard-of-Oz experiments in which a human experimenter (wizard) teleoperates a robotic head and eyes with his own head and eyes. Since the robot is animated based on the nonverbal behaviors of the human experimenter, the whole range of human eye movements can be presented without having to implement a complete gaze behavior model first. The experimenter watches and reacts to the video stream of the participant who directly interacts with the robot. Results are presented that focus on those technical aspects of the experimental platform that enable real-time and human-like interaction capabilities. In particular, the tracking of ocular motor dynamics, its replication in a robotic active vision system, and the involved teleoperation delays are evaluated. This setup will help to answer the question of which aspects of human gaze and head movement behavior have to be implemented to achieve humanness in active vision systems of robots.
Dementia care mapping: a review of the research literature.

PURPOSE The published literature on dementia care mapping (DCM) in improving quality of life and quality of care through practice development and research dates back to 1993. The purpose of this review of the research literature is to answer some key questions about the nature of the tool and its efficacy, to inform the ongoing revision of the tool, and to set an agenda for future research. DESIGN AND METHODS The DCM bibliographic database at the University of Bradford in the United Kingdom contains all publications known on DCM (http://www.bradford.ac.uk/acad/health/dcm). This formed the basis of the review. Texts that specifically examined the efficacy of DCM or in which DCM was used as a main measure in the evaluation or research were reviewed. RESULTS Thirty-four papers were categorized into five main types: (a) cross-sectional surveys, (b) evaluations of interventions, (c) practice development evaluations, (d) multimethod evaluations, and (e) papers investigating the psychometric properties of DCM. IMPLICATIONS These publications provide some evidence regarding the efficacy of DCM, issues of validity and reliability, and its use in practice and research. The need for further development and research in a number of key areas is highlighted.
Why Restaurants Fail

Past research on restaurant failures has focused mostly on quantitative factors and bankruptcy rates. This study explored restaurant ownership turnover rates using qualitative data, longitudinal data (1996-1999), and data from Dun and Bradstreet reports. In contrast to frequently repeated statistics, a relatively modest 26.16 percent of independent restaurants failed during the first year of operation. Results from this study indicated marginal differences in restaurant failures between franchise chains (57.2 percent) and independent operators (61.4 percent). Restaurant density and ownership turnover were strongly correlated (.9919). A qualitative analysis indicated that effective management of family life cycle and quality-of-life issues is more important than previously believed in the growth and development of a restaurant.
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.

BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%. RESULTS Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P=0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P=0.04). A total of 108 patients (17%) with nonmutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified. CONCLUSIONS Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, NCT00364013.).