Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor–Positive Breast Cancer

Importance Multiple molecular signatures are available for managing estrogen receptor (ER)–positive breast cancer but with little direct comparative information to guide the patient’s choice. Objective To conduct a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years. Design, Setting, and Participants This retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)–negative breast cancer. This analysis was performed as a preplanned secondary study of data from the Anastrozole or Tamoxifen Alone or Combined randomized clinical trial comparing 5-year treatment with anastrozole vs tamoxifen with 10-year follow-up data. The signatures included the Oncotype Dx recurrence score, PAM50-based Prosigna risk of recurrence (ROR), Breast Cancer Index (BCI), EndoPredict (EPclin), Clinical Treatment Score, and 4-marker immunohistochemical score. Data were collected from January 2009, through April 2015. Main Outcomes and Measures The primary objective was to compare the prognostic value of these signatures in addition to the Clinical Treatment Score (nodal status, tumor size, grade, age, and endocrine treatment) for distant recurrence for 0 to 10 years and 5 to 10 years after diagnosis. Likelihood ratio (LR) statistics were used with the &khgr;2 test and C indexes to assess the prognostic value of each signature. Results In this study of 774 postmenopausal women with ER-positive, ERBB2-negative disease (mean [SD] age, 64.1 [8.1] years), 591 (mean [SD] age, 63.4 [7.9] years) had node-negative disease. The signatures providing the most prognostic information were the ROR (hazard ratio [HR], 2.56; 95% CI, 1.96-3.35), followed by the BCI (HR, 2.46; 95% CI, 1.88-3.23) and EPclin (HR, 2.14; 95% CI, 1.71-2.68). Each provided significantly more information than the Clinical Treatment Score (HR, 1.99; 95% CI, 1.58-2.50), the recurrence score (HR, 1.69; 95% CI, 1.40-2.03), and the 4-marker immunohistochemical score (HR, 1.95; 95% CI, 1.55-2.45). Substantially less information was provided by all 6 molecular tests for the 183 patients with 1 to 3 positive nodes, but the BCI (&Dgr;LR &khgr;2 = 9.2) and EPclin (&Dgr;LR &khgr;2 = 7.4) provided more additional prognostic information than the other signatures. Conclusions and Relevance For women with node-negative disease, the ROR, BCI, and EPclin were significantly more prognostic for overall and late distant recurrence. For women with 1 to 3 positive nodes, limited independent information was available from any test. These data might help oncologists and patients to choose the most appropriate test when considering chemotherapy use and/or extended endocrine therapy. Trial Registration isrctn.com Identifier: ISRCTN18233230
Transcranial direct current stimulation for acute major depressive episodes: Meta-analysis of individual patient data

Background Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity. Aims To assess tDCS efficacy and to explore individual response predictors. Method Systematic review and individual patient data meta-analysis. Results Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38–4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22–4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12–0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS ‘doses' were, respectively, negatively and positively associated with tDCS efficacy. Conclusions The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose.
Precision measurements on trapped antihydrogen in the ALPHA experiment

Both the 1S–2S transition and the ground state hyperfine spectrum have been observed in trapped antihydrogen. The former constitutes the first observation of resonant interaction of light with an anti-atom, and the latter is the first detailed measurement of a spectral feature in antihydrogen. Owing to the narrow intrinsic linewidth of the 1S–2S transition and use of two-photon laser excitation, the transition energy can be precisely determined in both hydrogen and antihydrogen, allowing a direct comparison as a test of fundamental symmetry. The result is consistent with CPT invariance at a relative precision of around 2×10−10. This constitutes the most precise measurement of a property of antihydrogen. The hyperfine spectrum of antihydrogen is determined to a relative uncertainty of 4×10−4. The excited state and the hyperfine spectroscopy techniques currently both show sensitivity at the few 100 kHz level on the absolute scale. Here, the most recent work of the ALPHA collaboration on precision spectroscopy of antihydrogen is presented together with an outlook on improving the precision of measurements involving lasers and microwave radiation. Prospects of measuring the Lamb shift and determining the antiproton charge radius in trapped antihydrogen in the ALPHA apparatus are presented. Future perspectives of precision measurements of trapped antihydrogen in the ALPHA apparatus when the ELENA facility becomes available to experiments at CERN are discussed. This article is part of the Theo Murphy meeting issue ‘Antiproton physics in the ELENA era’.
The perceived causal structures of smoking: Smoker and non-smoker comparisons

Despite the detrimental impact of smoking on health, its prevalence remains high. Empirical research has provided insight into the many causes and effects of smoking, yet lay perceptions of smoking remain relatively understudied. This study used a form of network analysis to gain insight into the causal attributions for smoking of both smoking and non-smoking college students. The analyses resulted in highly endorsed, complex network diagrams that conveyed the perceived causal structures of smoking. Differences in smoker and non-smoker networks emerged with smokers attributing less negative consequences to smoking behaviors. Implications for intervention are discussed.
The Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire Using Mobile Technology: The MASK Study.

J Bousquet, MD , O VandenPlas, MD , M Bewick, MD , S Arnavielhe, PhD , A Bedbrook, BSc , R Murray, PhD , M van Eerd, MSc , J Fonseca, MD , M Morais-Almeida, MD , A Todo Bom, MD , AA Cruz, MD , F Sarquis Serpa, MD, 12 J da Silva, MD, 13 E Menditto, PhD, , G Passalacqua, MD , C Stellato , MD, 16 , MT Ventura, MD , D Caimmi, MD , P Demoly, MD , KC Bergmann, MD , T Keil, MD , L Klimek, MD , R Mösges, MD , S Shamai, MD, 22 T Zuberbier, MD , D Larenas-Linnemann, MD , M Rodriguez Gonzalez, MD, 24 MT Burguete Cabañas, MD, 25 D Ryan, MD , A Sheikh, MD , JM Anto, MD , J Mullol, MD , A Valero, MD 29 ML Kowalski, MD , P Kuna, MD , B Samolinski, MD , PV Tomazic, MD , S Bosnic-Anticevich, PhD , RE O'Hehir MD, , G De Vries, MSc , D Laune, PhD 5
The Dark Side of Going Abroad: How Broad Foreign Experiences Increase Immoral Behavior

Because of the unprecedented pace of globalization, foreign experiences are increasingly common and valued. Past research has focused on the benefits of foreign experiences, including enhanced creativity and reduced intergroup bias. In contrast, the present work uncovers a potential dark side of foreign experiences: increased immoral behavior. We propose that broad foreign experiences (i.e., experiences in multiple foreign countries) foster not only cognitive flexibility but also moral flexibility. Using multiple methods (longitudinal, correlational, and experimental), 8 studies (N > 2,200) establish that broad foreign experiences can lead to immoral behavior by increasing moral relativism—the belief that morality is relative rather than absolute. The relationship between broad foreign experiences and immoral behavior was robust across a variety of cultural populations (anglophone, francophone), life stages (high school students, university students, MBA students, middle-aged adults), and 7 different measures of immorality. As individuals are exposed to diverse cultures, their moral compass may lose some of its precision.
Analysis of Parent-of-Origin Effects on the X Chromosome in Asian and European Orofacial Cleft Triads Identifies Associations with DMD, FGF13, EGFL6, and Additional Loci at Xp22.2

Background: Although both the mother's and father's alleles are present in the offspring, they may not operate at the same level. These parent-of-origin (PoO) effects have not yet been explored on the X chromosome, which motivated us to develop new methods for detecting such effects. Orofacial clefts (OFCs) exhibit sex-specific differences in prevalence and are examples of traits where a search for various types of effects on the X chromosome might be relevant. Materials and Methods: We upgraded our R-package Haplin to enable genome-wide analyses of PoO effects, as well as power simulations for different statistical models. 14,486 X-chromosome SNPs in 1,291 Asian and 1,118 European case-parent triads of isolated OFCs were available from a previous GWAS. For each ethnicity, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) were analyzed separately using two X-inactivation models and a sliding-window approach to haplotype analysis. In addition, we performed analyses restricted to female offspring. Results: Associations were identified in “Dystrophin” (DMD, Xp21.2-p21.1), “Fibroblast growth factor 13” (FGF13, Xq26.3-q27.1) and “EGF-like domain multiple 6” (EGFL6, Xp22.2), with biologically plausible links to OFCs. Unlike EGFL6, the other associations on chromosomal region Xp22.2 had no apparent connections to OFCs. However, the Xp22.2 region itself is of potential interest because it contains genes for clefting syndromes [for example, “Oral-facial-digital syndrome 1” (OFD1) and “Midline 1” (MID1)]. Overall, the identified associations were highly specific for ethnicity, cleft subtype and X-inactivation model, except for DMD in which associations were identified in both CPO and CL/P, in the model with X-inactivation and in Europeans only. Discussion/Conclusion: The specificity of the associations for ethnicity, cleft subtype and X-inactivation model underscores the utility of conducting subanalyses, despite the ensuing need to adjust for additional multiple testing. Further investigations are needed to confirm the associations with DMD, EGF16, and FGF13. Furthermore, chromosomal region Xp22.2 appears to be a hotspot for genes implicated in clefting syndromes and thus constitutes an exciting direction to pursue in future OFCs research. More generally, the new methods presented here are readily adaptable to the study of X-linked PoO effects in other outcomes that use a family-based design.
Physical similarity or numerical representation counts in same–different, numerical comparison, physical comparison, and priming tasks?

Recent studies have highlighted the fact that some tasks used to study symbolic number representations are confounded by judgments about physical similarity. Here, we investigated whether the contribution of physical similarity and numerical representation differed in the often-used symbolic same–different, numerical comparison, physical comparison, and priming tasks. Experiment 1 showed that subjective physical similarity was the best predictor of participants’ performance in the same–different task, regardless of simultaneous or sequential presentation. Furthermore, the contribution of subjective physical similarity was larger in a simultaneous presentation than in a sequential presentation. Experiment 2 showed that only numerical representation was involved in numerical comparison. Experiment 3 showed that both subjective physical similarity and numerical representation contributed to participants’ physical comparison performance. Finally, only numerical representation contributed to participants’ performance in a priming task as revealed by Experiment 4. Taken together, the contribution of physical similarity and numerical representation depends on task demands. Performance primarily seems to rely on numerical properties in tasks that require explicit quantitative comparison judgments (physical or numerical), while physical stimulus properties exert an effect in the same–different task.
Value and usability of unpublished data sources for systematic reviews and network meta-analyses

Peer-reviewed publications and conference proceedings are the mainstay of data sources for systematic reviews and network meta-analyses (NMA), but access to informative unpublished data is now becoming commonplace. To explore the usefulness of three types of ‘grey’ literature-clinical trials registries, clinical study reports and data from regulatory authorities-we conducted four case studies. The reporting of outcome data in peer-reviewed publications, the clinical trials registries and the clinical study reports for two clinical trials—one in melanoma, one in juvenile idiopathic arthritis (JIA)—was examined. In addition, we assessed the value of including unpublished data from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) in evidence syntheses of hepatitis C virus (HCV) and chronic obstructive pulmonary disease (COPD), respectively. For the clinical trials in melanoma and JIA, we identified outcome parameters on ClinicalTrials.gov additional to those reported in the peer-reviewed publications: subgroup data and additional efficacy end points/extended follow-up, respectively. The clinical study report also provided results for several subgroups unavailable elsewhere. For HCV and COPD, additional outcome data were obtained from the EMA European Public Assessment Report (EPAR) and the FDA, respectively, including data on subgroups and mortality. We conclude that data from these grey literature sources have the potential to influence results of systematic reviews and NMAs, and may thus have implications for healthcare decisions. However, it is important to consider carefully the availability, reliability and consequent usability of these data sources in systematic reviews and NMAs.
The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia

Objectives Treatment-resistant schizophrenia (TRS) continues to be a challenge in modern psychiatry. Most of these patients have severe neurocognitive deficits. Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of TRS, but because of potential neurocognitive adverse effects, it is associated with many controversies. The aim of this prospective, open study was to evaluate the effects of ECT augmentation of antipsychotics on cognitive functions in patients with TRS. Methods Overall, 31 inpatients with TRS were included, 16 men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical symptoms and global impression, as well as verbal memory, visual memory, working memory, psychomotor speed, verbal fluency, and executive functioning, was conducted before and after the completion of ECT treatment. Results We ran a series of paired-samples t tests, and the Bonferroni adjustment for multiple comparisons reduced the significance level to P = 0.004. The neurocognitive domains that demonstrated statistically significant improvement were immediate and delayed verbal memory, and executive functioning, whereas statistical trend was observed for visual memory and psychomotor speed. None of the neurocognitive functions exhibited significant deterioration after the ECT treatment. Electroconvulsive therapy was effective in reducing general symptoms of schizophrenia, resulting in more than 30% decrease in the overall symptom severity measured by the Positive and Negative Syndrome Scale. Conclusions Notwithstanding some limitations of this study, the combination of ECT and antipsychotics has improved several neurocognitive domains, without evidence of worsening of any cognitive functions.
Designing with interactive example galleries

Designers often use examples for inspiration; examples offer contextualized instances of how form and content integrate. Can interactive example galleries bring this practice to everyday users doing design work, and does working with examples help the designs they create? This paper explores whether people can realize significant value from explicit mechanisms for designing by example modification. We present the results of three studies, finding that independent raters prefer designs created with the aid of examples, that examples may benefit novices more than experienced designers, that users prefer adaptively selected examples to random ones, and that users make use of multiple examples when creating new designs. To enable these studies and demonstrate how software tools can facilitate designing with examples, we introduce interface techniques for browsing and borrowing from a corpus of examples, manifest in the Adaptive Ideas Web design tool. Adaptive Ideas leverages a faceted metadata interface for viewing and navigating example galleries.
PTEN Loss Promotes Intratumoral Androgen Synthesis and Tumor Microenvironment Remodeling via Aberrant Activation of RUNX2 in Castration-Resistant Prostate Cancer

Purpose: Intratumoral androgen synthesis (IAS) is a key mechanism promoting androgen receptor (AR) reactivation and antiandrogen resistance in castration-resistant prostate cancer (CRPC). However, signaling pathways driving aberrant IAS remain poorly understood. Experimental Design: The effect of components of the AKT-RUNX2-osteocalcin (OCN)–GPRC6A–CREB signaling axis on expression of steroidogenesis genes CYP11A1 and CYP17A1 and testosterone level were examined in PTEN-null human prostate cancer cell lines. Pten knockout mice were used to examine the effect of Runx2 heterozygous deletion or abiraterone acetate (ABA), a prodrug of the CYP17A1 inhibitor abiraterone on Cyp11a1 and Cyp17a1 expression, testosterone level and tumor microenvironment (TME) remodeling in vivo. Results: We uncovered that activation of the AKT–RUNX2–OCN–GPRC6A–CREB signaling axis induced expression of CYP11A1 and CYP17A1 and testosterone production in PTEN-null prostate cancer cell lines in culture. Deletion of Runx2 in Pten homozygous knockout prostate tumors decreased Cyp11a1 and Cyp17a1 expression, testosterone level, and tumor growth in castrated mice. ABA treatment also inhibited testosterone synthesis and alleviated Pten loss-induced tumorigenesis in vivo. Pten deletion induced TME remodeling, but Runx2 heterozygous deletion or ABA treatment reversed the effect of Pten loss by decreasing expression of the collagenase Mmp9. Conclusions: Abnormal RUNX2 activation plays a pivotal role in PTEN loss-induced IAS and TME remodeling, suggesting that the identified signaling cascade represents a viable target for effective treatment of PTEN-null prostate cancer, including CRPC. Clin Cancer Res; 24(4); 834–46. ©2017 AACR.
Learning to Play with Intrinsically-Motivated Self-Aware Agents

Infants are experts at playing, with an amazing ability to generate novel structured behaviors in unstructured environments that lack clear extrinsic reward signals. We seek to mathematically formalize these abilities using a neural network that implements curiosity-driven intrinsic motivation. Using a simple but ecologically naturalistic simulated environment in which an agent can move and interact with objects it sees, we propose a "world-model" network that learns to predict the dynamic consequences of the agent's actions. Simultaneously, we train a separate explicit "self-model" that allows the agent to track the error map of its own world-model, and then uses the self-model to adversarially challenge the developing world-model. We demonstrate that this policy causes the agent to explore novel and informative interactions with its environment, leading to the generation of a spectrum of complex behaviors, including ego-motion prediction, object attention, and object gathering. Moreover, the world-model that the agent learns supports improved performance on object dynamics prediction, detection, localization and recognition tasks. Taken together, our results are initial steps toward creating flexible autonomous agents that self-supervise in complex novel physical environments.
Approach–avoidance coping conflict in a sample of burn patients at risk for posttraumatic stress disorder

Background: Following an acute burn injury, higher distress is consistently observed among individuals exhibiting a conflict between approach coping (e.g., processing) and avoidance coping (e.g., suppression) relative to those individuals who use only one of these methods. Study objectives were to determine if contradictory coping messages would lead to such approach–avoidance coping conflict and to determine if experiment‐induced coping conflict is also associated with higher distress. Methods: Participants (n=59 adults hospitalized with acute burn injuries) were assigned randomly to experimental conditions differing in the order in which training was provided in two ways of coping with posttrauma re‐experiencing symptoms (i.e., process‐then‐suppress versus suppress‐then‐process). The primary dependent variable was coping behavior during the 24‐hr posttraining period. Coping behavior was categorized as approach coping (processing), avoidance coping (suppressing), or approach–avoidance coping conflict (both) on the basis of median splits on subscales assessing these behaviors. Secondary analyses examined the relationship between this experiment‐induced coping conflict and re‐experiencing symptoms. Results: Results indicated that participants in the process‐then‐suppress condition, relative to the suppress‐then‐process condition, were significantly more likely to exhibit approach–avoidance coping conflict (i.e., above median split on both processing and suppressing) during the next 24 hr. Furthermore, approach–avoidance coping conflict was associated with greater re‐experiencing symptoms assessed via self‐report and by blinded coding of recorded speech. Conclusions: It is concluded that the order of coping skill training can influence treatment outcome, success of coping methods, and overall levels of distress. therefore, training in stabilizing and calming methods should precede training in active processing following stressful life events. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.
Differentially Private ANOVA Testing

Modern society generates an incredible amount of data about individuals, and releasing summary statistics about this data in a manner that provably protects individual privacy would offer a valuable resource for researchers in many fields. We present the first algorithm for analysis of variance (ANOVA) that preserves differential privacy, allowing this important statistical test to be conducted (and the results released) on databases of sensitive information. In addition to our private algorithm for the F test statistic, we show a rigorous way to compute p-values that accounts for the added noise needed to preserve privacy. Finally, we present experimental results quantifying the statistical power of this differentially private version of the test, finding that a sample of several thousand observations is sufficient to detect variation between groups. The differentially private ANOVA algorithm is a promising approach for releasing a common test statistic that is valuable in fields in the sciences and social sciences.