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Background: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown. Methods: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3. Results: High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release. Conclusion: Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.

To tackle the plastic problem, the worldwide campaign &lsquo, Plastic Free July&rsquo, aims at encouraging people to reduce single-use plastics during the month of July. To get people started with new behavior patterns, so-called &lsquo, windows of opportunity&rsquo, &mdash, periods where people become open for new experiences&mdash, are expected to matter. Therefore, the current study evaluated if an arbitrary month that is framed as an opportunity for change can interrupt people in their daily routines and reduce plastic consumption. An online survey (n = 509) with repeated measures (n = 366) was conducted including one experimental and one control group. The experimental group was invited to reduce their single-use plastic consumption during July in line with the &lsquo, campaign. Results revealed that, in this action period, single-use plastic consumption was slightly but significantly lower in the experimental than in the control group, which did not receive any information about &lsquo, The campaign seemed to be more effective for participants with low pro-environmental identity. Path analysis revealed that plastic consumption (prior to the intervention) was significantly predicted by perceived difficulty, habits, and pro-environmental identity. Policy support was predicted by problem awareness, pro-environmental identity and perceived barriers. We conclude with recommendations for plastic-free purchase and policy support.

There is an active debate regarding whether the ego depletion effect is real. A recent pre-registered experiment with the Stroop task as the depleting task and the antisaccade task as the outcome task found a medium level effect size. In the current research, we pre-registered a multi-lab collaborating project to replicate that experiment. Data from twelve labs across the globe (N = 1775) revealed a small but significant ego depletion effect, g = 0.12, CI95 = [0.02, 0.21]. The data also provided some evidence in support of a moderating effect of individual differences in lay theory about willpower, such that participants with an unlimited-resource theory evinced a weaker depletion effect. Finally, a series of auxiliary analyses provided important implications for future studies investigating the robustness of ego depletion, such that strictly controlled experimental settings and outcome tasks with medium difficulty might be better for observing a stronger depletion effect.

Structural approaches to personality have brought about considerable progress in description and prediction of interindividual differences in thoughts, feelings, and behavior. However, in order to move towards personality psychology as an explanatory science, we argue that structural, process-oriented and developmental approaches to personality have to be integrated. We summarize the main propositions of a theoretical framework published in a target article in the European Journal of Personality (Baumert et al., 2017a), and highlight the resulting challenges for future personality research.

Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy.

This article proposes an optical measurement of movement applied to data from video recordings of facial expressions of emotion. The approach offers a way to capture motion adapted from the film industry in which markers placed on the skin of the face can be tracked with a pattern-matching algorithm. The method records and postprocesses raw facial movement data (coordinates per frame) of distinctly placed markers and is intended for use in facial expression research (e.g., microexpressions) in laboratory settings. Due to the explicit use of specifically placed, artificial markers, the procedure offers the simultaneous measurement of several emotionally relevant markers in a (psychometrically) objective and artifact-free way, even for facial regions without natural landmarks (e.g., the cheeks). In addition, the proposed procedure is fully based on open-source software and is transparent at every step of data processing. Two worked examples demonstrate the practicability of the proposed procedure: In Study 1(N= 39), the participants were instructed to show the emotions happiness, sadness, disgust, and anger, and in Study 2 (N= 113), they were asked to present both a neutral face and the emotions happiness, disgust, and fear. Study 2 involved the simultaneous tracking of 14 markers for approximately 12 min per participant with a time resolution of 33 ms. The measured facial movements corresponded closely to the assumptions of established measurement instruments (EMFACS, FACSAID, Friesen & Ekman, 1983; Ekman & Hager, 2002). In addition, the measurement was found to be very precise with sub-second, sub-pixel, and sub-millimeter accuracy.

Background Elevated levels of intratumoral uPA and PAI-1 in ELISA-based measurements are associated with a high recurrence risk and allow to identify patients who might particularly benefit from adjuvant chemotherapy. The clinical utility of ELISA-based protein analysis is, however, greatly limited by the requirement of fresh tumor tisssue. We have therefore evaluated in a large clinical trial patient cohort with long-follow-up whether immunohistochemical detection of uPA and PAI-1 in FFPE archived tumor samples is also able to identify women with poor prognosis. Patients and Methods 547 postmenopausal women with hormone receptor–positive, early breast cancer who had received at least 5 years of endocrine therapy in the prospectively designed ABCSG-06 trial, and in whom FFPE tumor tissue was available, were included in this analysis. uPA and PAI-1 protein expression was evaluated by immunohistochemistry, and correlated with distant-disease free (DDFS) and overall survival (OS). Results Stromal co-expression of uPA and PAI-1 was detected in 166 of 276 (60%) evaluable tumor samples and was weakly associated with tumor size (p=0.012, Chi Square test) but not with age, nodal status, grading, or receptor status. Women with intratumoral uPA/PAI-1 expression were more likely to have a shorter DDFS in multivariate analysis (HR for relapse p=1.870; 95% CI 1.184-2.955; p=0.007 Cox regression analysis) and and OS (adjusted HR for death p=1.291; 95% CI 0.928-1.795; p=0.129) than women without. After a median follow-up of 10 years, women with uPA/PAI-1-positive tumors experienced a significantly shorter DDFS (p Conclusions Stromal co-expression of uPA and PAI-1 in breast cancer samples predicts poor DDFS and OS in postmenopausal women with hormone-receptor positive early-stage breast cancer who receive endocrine therapy. Citation Format: Singer CF, Filipits M, Jahn S, Abete L, Jakesz R, Greil R, Bauernhofer T, Kwasny W, Seifert M, Fitzal F, Schmitt M, Moinfar F, Gnant M. Stromal co-expression of urokinase-type plasminogen activator (uPA) and plasminogen activator Inhibitor (PAI-1) protein by IHC predicts poor disease outcome in endocrine-treated postmenopausal patients with receptor-positive early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-21.

Justice-related situations are a part of studentsʼ everyday life. In order to test the antecedents, correlates, and consequences of (in)justice in school, valid measures of justice are needed. To our knowledge, this is the first study to develop an observer low inference rating instrument that can be applied to measure justice in the primary classroom. In two pre-studies, justice-relevant situations in the classroom were extracted and observable indicators for these situations were developed. In the main study, this instrument was used to observe 208 primary school students with regard to their experiences of justice or injustice. In addition to this, other measures of justice were developed to examine the convergence between observer low inference ratings of classroom justice and high inference rating instruments for teachers, students, and external observers. Factor analyses and correlations between the different indices of the observer low inference rating and the high inference rating items suggested that incidents of justice and injustice in the classroom do not tend to co-occur frequently. Teachers do not appear to have a general tendency to treat a child more or less justly across a large number of situations. The findings suggest that a comprehensive assessment of classroom justice requires a multi-method approach where the justice ratings of students, teachers and external observers are all taken into consideration.

Both school achievement goals (mastery, performance approach, performance avoidance goals) and well-being goals (work avoidance, affiliation goals) are important predictors of learning and achievement related outcomes. However, disagreement exists regarding the definition of goals as relatively stable traits versus situational states that react sensitive to contexts. This paper presents the development of an inventory for the assessment of students’ multiple state and trait goals. In Study 1, students (N = 196) answered the trait items. The results of an exploratory factor analysis indicated the construct validity of the goals. In Study 2, students completed trait and state scales in different weeks (N = 542) and repeatedly after 12 weeks each. Confirmatory factor analyses as well as correlations with state and trait reference constructs confirmed the convergent and differential validity of both the trait and the state goal factors. The instrument offers a brief, reliable, and valid measure of multiple state and trait goals. Latent state trait analyses revealed that some state goals are surprisingly robust against situational influences and equally stable across time as corresponding trait goals, whereas other goals are more dependent on the learning situation.

Applying an experimental between-subject design with varying situational demands ( N = 168) we investigated the main and interactive effects of perfectionistic strivings (PS) and perfectionistic concerns (PC) on primary threat appraisal and secondary self-confidence appraisal and if these appraisals mediate the effects of PS and PC on the affective stress-response to a given situation. Path analyses revealed differential effects of experimental condition, PS and PC on the cognitive appraisals and the affective stress response. While the positive effects of PS on cognitive appraisals did not extend to the affective stress response directly or indirectly, the negative effect of PC on the affective stress response was fully mediated by the secondary self-confidence appraisal. Additionally we found a significant three-way interaction of PS, PC and experimental condition predicting the affective stress response that was not mediated by the cognitive appraisals.

miR-221/-222 and components of the urokinase-type plasminogen activator system (uPAS) are associated with metastasis and poor prognosis in breast cancer, including the triple-negative subtype (TNBC). Modification of components of uPAS and involved miRNAs may contribute to targeted therapy for breast cancer patients. miR-221-/-222-overexpressing or miR-221-depleted cells were employed for qRT-PCR and Western blots to show associations of uPAR with miR-221/-222. To substantiate direct targeting of miR-221/-222 within 3' UTR of the uPAR isoform 2, in silico analysesand in vitro assays were conducted. Significant associations between miR-221 and uPAR isoform 2 expressions were observed at the mRNA and protein levels in breast cancer cells representing TNBC. For the first time, the uPAR isoform 2 was demonstrated as direct target for miR-221/-222. Inhibition of miR-221 reduced uPAR protein expression and expression of the tumor cell invasion markers vimentin and RHOC. These results demonstrate a direct and positive regulation of the secreted uPAR isoform 2 by miR-221, increasing its protein expression, a prerequisite for malignancy, while the other uPAR isoforms (1, 3 and 4) are indirectly regulated through miR-10b and miR-221/-222. By targeting uPAR isoforms and/or miRNA-221/-222, the diagnosis and therapy of breast cancer, in particular in TNBC, could be significantly improved.

Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer subgroup with poor prognosis; survival rates are likely to be lower with TNBC compared to other breast cancer subgroups. For this disease, systemic adjuvant chemotherapy regimens often yield suboptimal clinical results. To improve treatment regimens in TNBC, identification of molecular biomarkers may help to select patients for individualized adjuvant therapy. Evidence has accumulated that determination of the methylation status of the PITX2 gene provides a predictive value in various breast cancer subgroups, either treated with endocrine-based therapy or anthracycline-containing chemotherapy. To further explore the validity of this novel predictive candidate biomarker, in the present exploratory retrospective study, determination of the PITX2 DNA-methylation status was assessed for non-metastatic TNBC patients treated with adjuvant anthracycline-based chemotherapy by molecular analysis of breast cancer tissues. The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to disease-free and overall survival, applying an optimized DNA-methylation score of 6.35%. For non-metastatic TNBC patients treated with adjuvant systemic anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (

Im Diskurs um eine nachhaltige Entwicklung ist unter anderem die Frage nach distributiver Gerechtigkeit, das heist der gerechten Verteilung von begrenzten Ressourcen, von hoher Bedeutung Dem Bildungsbereich wird hier eine bedeutende Rolle zugewiesen, Individuen soll der Kompetenzerwerb zur Gestaltung einer nachhaltigen Zukunft ermoglicht werden. Ziel dieses Beitrages ist es, aufzuzeigen, dass es in diesem Kontext auch notwendig ist, die Institutionen selbst als Orte zu gestalten, die als gerecht wahrgenommen werden, da diese wichtige Sozialisationsinstanzen darstellen. Psychologische Erkenntnisse bezuglich der Wahrnehmung und der Effekte von Gerechtigkeit konnen Hinweise dazu liefern, wie Schule gestaltet werden konnte, um zur Leitidee einer nachhaltigen Entwicklung beizutragen. Hier sind Modelle zur Gerechtigkeitswahrnehmung und relevante Personlichkeitskonstrukte wie der Gerechte-Welt-Glauben oder die Ungerechtigkeitssensibilitat von Bedeutung. Die hier vorgestellten empirischen Ergebnisse stellen nachhaltigkeitsrelevante Effekte von erfahrener (Un)gerechtigkeit im Schulalltag vor. Hieraus lassen sich Implikationen sowohl fur die Lehrerbildung als auch fur die Schulorganisation ableiten.

School can be regarded as an important factor in the development of children’s values and attitudes. Given this great importance of justice experiences for students’ development, this study aimed at examining the influence of perceived injustice in school on students’ emotions, well-being, and behavior with an experimental longitudinal design. In total, 196 students participated in this study and came to the university with their classes to receive extra teaching once a week for six consecutive weeks. To manipulate justice perceptions, a scenario of arbitrary privilege was chosen to lead students of the experimental group to experience injustice from a beneficiary perspective. We found that students in the experimental group reported higher well-being and a higher appreciation of the opportunity to learn than the control group did. Additionally, they showed an increase in justice-related negative emotions over time; that is, they expressed more of a bad conscience and stronger feelings of anger the more they became aware of their privilege. This study shows that even subtle experiences of injustice in school can have an impact on students’ outcomes. These results are discussed with regard to practical implications.

SummaryLittle is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the PITX2 (paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application of PITX2 as a predictive biomarker to personalize breast cancer management.

The Nonlinear Interaction of Person and Situation (NIPS) Model (Schmitt et al., 2013) is a descriptive model that designates how personality traits and functionally equivalent characteristics of the situation interactively shape behavior. On the basis of the mathematical form of this model (i.e., a logistic function), we suggest the NIPS Process Model. Using previous results from item response theory and psychophysics, we determined which processes have to be considered in the person-situation interaction. The NIPS Process Model consists of four elements: activation (supplied by person’s threshold and situation’s demands), tendency (supplied by person’s bias and situation’s alternatives), inhibition (supplied by person’s avoidance and situation’s restrictions), and predictability (supplied person’s variability and situation’s selectivity). It systematically assembles the factors that influence behavior and is applicable to many psychological fields. It can be used to reflect on relations between process models in various psychological disciplines and provides guidelines for much-needed future research.

Following primary debulking surgery, the presence of a residual tumor mass is one of the most important prognostic factors in ovarian cancer. In a previous study, we established the OVSCORE, an algorithm to predict surgical outcome, based on the clinical factors of nuclear grading and ascitic fluid volume, plus the cancer biomarkers, kallikrein-related peptidases (KLKs), KLK6 and KLK13. In the present study, OVSCORE performance was tested in an independent ovarian cancer patient cohort consisting of 87 patients. The impact of KLKs, KLK5, 6, 7 and 13 and other clinical factors on patient prognosis and outcome was also evaluated. The OVSCORE proved to be a strong and statistically significant predictor of surgical success in terms of area under the receiver operating characteristic curve (ROC AUC, 0.777), as well as positive and negative predictive value in this independent study group. KLK6 and 13 individually did not show clinical relevance in this cohort, but two other KLKs, KLK5 and KLK7, were associated with advanced FIGO stage, higher nuclear grade and positive lymph node status. In the multivariate Cox regression analysis for overall survival (OS), KLK7 had a protective impact on OS. This study confirms the role of KLKs in ovarian cancer for surgical success and survival, and validates the novel OVSCORE algorithm in an independent collective. As a key clinical application, the OVSCORE could aid gynecological oncologists in identifying those ovarian cancer patients unlikely to benefit from radical surgery who could be candidates for alternative therapeutic approaches.

Although moral courage is a highly desirable behavior whose determinants need to be understood, research has largely neglected the emotions involved in moral courage. Does anger about the norm violation or (anticipated) guilt enhance such interventions even if general mood does not? As previous studies have often failed to overcome the limitations of self-reported emotions and the use of behavior intention measures, we used a multimethod emotion measurement while observing real behavior. By realizing a real theft scenario in the laboratory (N = 68), we found that anger but neither guilt nor general mood predicted intervention behavior. Our findings complement and expand previous studies by showing that people who experience and express anger more strongly are able to overcome the psychological barrier of potential negative (social) consequences in a situation in which a fast and immediate intervention is needed, whereas others stand and watch. Copyright © 2014 John Wiley & Sons, Ltd.

Other-related concerns for justice are fundamental components of morality and interpersonal behaviors. In this paper, we investigated macro/cultural and micro/individual differences in justice concerns for others. More specifically, beneficiary sensitivity (BS) and observer sensitivity (OS) were compared across China as a typical collectivist society, and Germany and Russia as two individualistic societies. Individualism-collectivism was assumed to mediate the cultural variance of BS and OS. In Study 1, Chinese participants exhibited more BS but less OS compared to German participants. In Study 2, the Chinese participants exhibited more BS but not significantly different OS compared to Russian participants. Moreover, collectivism mediated this cultural difference in BS but not OS. In Study 3, collectivist participants identified according to their proposals in social value games exhibited more BS than did individualistic participants, while the two groups revealed no significant difference in OS. Taken together, our studies consistently show that higher collectivism both on the cultural and individual levels is related to BS but not to OS, suggesting that collectivist values make people sensitive to self-advantage in comparison to the suffering of others.

MALDI mass spectrometry imaging (MSI) has rapidly established itself as a powerful biomarker discovery tool. To date, no formal investigation has assessed the center-to-center comparability of MALDI MSI experiments, an essential step for it to develop into a new diagnostic method. To test such capabilities, we have performed a multicenter study focused on biomarkers of stromal activation in breast cancer. MALDI MSI experiments were performed in two centers using independent tissue banks, infrastructure, methods, and practitioners. One of the data sets was used for discovery and the other for validation. Areas of intra- and extratumoral stroma were selected, and their protein signals were compared. Four protein signals were found to be significantly associated with tumor-associated stroma in the discovery data set measured in Munich. Three of these peaks were also detected in the independent validation data set measured in Leiden, all of which were also significantly associated with intratumoral stroma. Hierarchical clustering displayed 100% accuracy in the Munich MSI data set and 80.9% accuracy in the Leiden MSI data set. The association of one of the identified mass signals (PA28) with stromal activation was confirmed with immunohistochemistry performed on 20 breast tumors. Independent and international MALDI MSI investigations could identify validated biomarkers of stromal activation.

Consensus obtained in personality judgments based on thin slices of behavior was examined by manipulating the shared meaning of the traits being judged, the accountability for the judgments, and the amount of target information. 160 judges rated a total of 60 teachers on the Big Five personality dimensions. Consensus was approached from a judge and from a target perspective. A shared meaning had a negative effect on consensus in Extraversion ratings. Accountability had a consistently negative effect across consensus perspectives. A positive effect for amount of target information was found for Neuroticism. Additionally, it was shown that, under different conditions, judgments were based more or less on shared stereotypes. Results suggest that the degree to which we agree on our judgments of others can easily be manipulated by external influences, thus involving significant practical implication for various contexts.

International guidelines recommend anthracycline-based chemotherapy for high-risk breast cancer patients as the standard-of-care, but not all patients do equally benefit from such a chemotherapy. The novel therascreen® PITX2 RGQ PCR assay is a quantitative in vitro methylation-specific real-time PCR test (qMSP), intended for the determination of the percent methylation ratio (PMR) in the pituitary homeobox 2 (PITX2) promoter 2 expressed by primary breast cancer tumor tissue (FFPE-material). After bisulfite exposure of extracted DNA to distinguish between methylated and non-methylated PITX2 DNA, the percent methylation ratio (PMR) of the PITX2 gene promoter 2 is quantified by qMSP. The PMR obtained does provide information to the treating physician about whether a patient is likely to respond to anthracycline-based chemotherapy. Data will be presented for 205 high-risk lymph node-positive, estrogen receptor-positive, HER2-negative breast cancer patients, treated with adjuvant anthracycline-based chemotherapy. The PITX2 pre-defined cut-off value of PMR = 12 demonstrated a statistically significant differentiation between low- and high-risk breast cancer patient for the primary endpoint DFS, also for patients treated with endocrine therapy in addition to anthracycline-based adjuvant therapy. High-risk lymph node-positive, estrogen-receptor-positive, HER2-negative breast cancer patients, with PITX2 methylation defined as low (PMR ≤ 12), are sufficiently treated with anthracycline-based chemotherapy, irrespective if treated with additional tamoxifen. High-risk lymph node-positive, estrogen receptor-positive, HER2-negative breast cancer patients with PITX2 methylation defined as high (PMR > 12) should avoid anthracycline-based chemotherapy. These patients are recommended to switch to other chemotherapy regimens, since with this PITX2-characteristics, the patient has a lower probability to respond to anthracycline-based chemotherapy.

The psychometric properties of behaviors in economic games as indicators of stable latent dispositions of altruism and fairness were tested in two studies. Using latent state-trait analyses, we explored the factor structure of offers in the dictator game, rejection decisions in the ultimatum game, and altruistic punishment and altruistic compensation in a three-person game. Results showed that four distinct but intercorrelated latent dispositions best described the interindividual differences in these behaviors. The reliabilities and stabilities of these behaviors across 6 weeks were generally moderate to high. Correlations with self-report measures of personality suggested that offers in the dictator game and altruistic compensation reflect a concern for fairness coupled with a reluctance to harm others. Rejection decisions in the ultimatum game were correlated with competitiveness and the need for power. In sum, our results suggest that economic games have good psychometric qualities as instruments that can be used to assess stable latent dispositions and can be employed as objective personality tests sensu Cattell to gain a more complete picture of personality beyond self-reports.

The use of objective behavioral indicators instead of selfreported behaviors and self-ratings has a long history in personality assessment. The basic idea of objective personality tests (OPTs) can be traced back to James McKeen Cattell’s proposal of mental tests in 1890. A few decades later, OPT procedures were employed by the German and US militaries during World War II (see Fitts, 1946). Until today, most tests designed for the objective assessment of personality have been based on Raymond Bernard Cattell’s comprehensive theoretical and empirical work and his well-known postulate that a complete investigation of personality requires heterogeneous data sources including self-report data (Q-data), life indicators of personality often obtained from observer reports (L-data), and objective performance

Background. Tumor tissue-associated KLKs (kallikrein-related peptidases) are clinically important biomarkers that may allow prognosis of the cancer disease and/or prediction of response/failure of cancer patients to cancerdirected drugs. Regarding the female/male reproductive tract, remarkably, all of the fifteen KLKs are expressed in the normal prostate, breast, cervix uteri, and the testis, whereas the uterus/endometrium and the ovary are expressing a limited number of KLKs only. Conclusions. Most of the information regarding elevated expression of KLKs in tumor-affected organs is available for ovarian cancer; depicting them as valuable biomarkers in the cancerous phenotype. In contrast, for breast cancer, a series of KLKs was found to be downregulated. However, in breast cancer, KLK4 is elevated which is also true for ovarian and prostate cancer. In such cases, selective synthetic KLK inhibitors that aim at blocking the proteolytic activities of certain KLKs may serve as future candidate therapeutic drugs to interfere with tumor progression and metastasis.

Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

On the basis of an integration of dual–process models of information processing and the lens model framework of person perception, we conducted two studies to investigate whether self–perceivers could detect their implicit disposition from video feedback of behavioural cues and whether these cues were used for explicit dispositional inferences under conditions that maximized the presumed self–perception process. Using an approach that differed from previous research, we used the following: (i) a more detailed and stepwise self–perception procedure; (ii) a specific explicit measure compared with a global explicit measure; and (iii) disgust sensitivity as a domain with clear, unambiguous cues and an assumed low self–presentation bias. The results from two studies (N = 117 and N = 130) on disgust sensitivity provide the first evidence for the assumed process with regard to bodily reaction cues but not with regard to facial expression cues. These novel findings suggest that people can get to know their unconscious selves better if supporting conditions are met and the right behavioural cues are attended to. Additional boundary conditions of this self–perception process were investigated using display rules and need for closure in Study 2. Copyright © 2013 John Wiley & Sons, Ltd.

Moral courage is characterized as a bystander intervention against the norm violations of a perpetrator despite the potential for negative consequences for oneself. We tested a comprehensive set of potential personality determinants of moral courage derived from a model of helping. In Study 1, we used a vignette to assess the self-reported willingness to intervene against a theft. In Study 2, the theft was put into effect, and behavioral reactions were observed. The results of Study 1 showed that moral disengagement, self-efficacy, and social anxiety, which are traits that are known to predict helping, were also related to moral courage intentions. Differently, in Study 2, real moral courage was predicted only by beneficiary sensitivity, a disposition that captures perceptual readiness and affective reactivity to perceived injustice. Our results provide insights into the processes involved in moral courage in a realistic situation and stress the importance of behavioral observations.

Being a teacher is known to be a particularly stressful occupation and as a consequence many teachers suffer from reduced well-being. Thus, it is important to know as soon as possible which individuals are likely to experience reduced well-being in their employment. Therefore, this study investigated whether it is possible to infer teachers’ future well-being from minimal nonverbal information, i.e., thin slices of behavior. Between 2003 and 2006, 50 teachers were filmed while holding a lesson. Naive observers were shown 60-s clips of these teachers and were asked to predict the teachers’ satisfaction with job, life, and health in 5–8 years. Five to eight years later, the teachers’ satisfaction with job, life, and health was assessed. It was shown that judges highly agree in their predictions. Additionally, these predictions were shown to be accurate for life and job satisfaction. Thus, it is possible to predict a teacher’s well-being on the basis of thin slices of the nonverbal behavior they show while performing their job. These thin slices might therefore allow for a risk assessment in the context of teacher education and such approaches might contribute to teacher professionalism.

At present, it is not well understood which individual characteristics determine whether individuals will benefit or suffer from feedback about suboptimal performance. Three separate studies tested the idea that individuals‘ reactions to (neutral versus negative; positive versus negative) feedback as either improving or deteriorating performance in intelligence tests depended on their explicit and implicit self–concept of intelligence (eSCI and iSCI). In all studies (Study 1, N = 177; Study 2, N = 165; Study 3, N = 132), persons with low eSCI/high iSCI showed a boost in performance after negative feedback, whereas persons with any other combination showed a decline in performance. The studies also provide an explanation for these effects in terms of mediating mechanisms. Whereas the performance boost of individuals with low eSCI/high iSCI can be best explained by achievement–related reactance (Studies 2 and 3) and decrease in ruminative thinking (Study 3), the performance declines in the other configurations were mediated by decreased achievement motivation, increased frustration and increased outrage (Study 3). All these mediating mechanisms proved independent and incremental in a bootstrapping–based moderated meditation analysis. The results are discussed in light of the construct validity of our Implicit Association Test (IAT) and IATs in general. Copyright © 2013 John Wiley & Sons, Ltd.

Depression is one of the most clinically relevant mood disorders, and many assessment instruments have been developed to measure it. Probably the most frequently used instrument is Beck’s Depression Inventory (BDI). The simplified BDI (BDI-S) is a more efficient version of the BDI that has been shown to be no less reliable or valid. As the BDI-S has not yet been subjected to rigorous tests of Item Response Theory, it is the aim of the present paper to conduct such an analysis using the Rasch model. This study subjected a simplified version of the BDI consisting of 20 items (BDI-S20) to a Rasch analysis in a sample of N = 5,035 participants. The scale, minus one misfitting item (BDI-S19), yielded a good approximation to Rasch assumptions. Moderate differential item functioning (DIF) was present. It is concluded that the BDI-S19 is an internally valid instrument for assessing depression, although some room for improvement exists.

In this target article, we argue that personality processes, personality structure, and personality development have to be understood and investigated in integrated ways in order to provide comprehensive responses to the key questions of personality psychology. The psychological processes and mechanisms that explain concrete behaviour in concrete situations should provide explanation for patterns of variation across situations and individuals, for development over time as well as for structures observed in intra–individual and inter–individual differences. Personality structures, defined as patterns of covariation in behaviour, including thoughts and feelings, are results of those processes in transaction with situational affordances and regularities. It cannot be presupposed that processes are organized in ways that directly correspond to the observed structure. Rather, it is an empirical question whether shared sets of processes are uniquely involved in shaping correlated behaviours, but not uncorrelated behaviours (what we term ‘correspondence’ throughout this paper), or whether more complex interactions of processes give rise to population–level patterns of covariation (termed ‘emergence’). The paper is organized in three parts, with part I providing the main arguments, part II reviewing some of the past approaches at (partial) integration, and part III outlining conclusions of how future personality psychology should progress towards complete integration. Working definitions for the central terms are provided in the appendix. Copyright © 2017 European Association of Personality Psychology

High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and theHER2receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of thePITX2(paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application ofPITX2as a predictive biomarker to personalize breast cancer management.

According to self-determination theory, the satisfaction of the basic needs for autonomy, competence, and relatedness influences achievement emotions and situational interest. The present study investigated whether domain-specific explicit need strength moderated the impact of need satisfaction/dissatisfaction on the outcomes achievement emotions and situational interest. Self-report measures of domain specific need strength, perceived need satisfaction/dissatisfaction, achievement emotions (joy and boredom), and situational interest (catch-SI and hold-SI) were completed by 220 students attending 8th and 9th grade. Explicit need strength moderated the impact of perceived need satisfaction on hold-SI. Additionally, need strength moderated the impact of perceived need dissatisfaction on joy, boredom, and hold-SI. Nevertheless, need satisfaction had greater predictive power than need strength and the interaction effects appeared more consistently with the predictor perceived need dissatisfaction. Thus, need satisfaction seems to be the main explanatory variable for the outcomes. Conclusions are discussed.

SummaryKallikrein-related peptidases (KLK), which represent a major tissue-associated proteolytic system, stand for a rich source of biomarkers that may allow molecular classification, early diagnosis and prognosis of human malignancies as well as prediction of response or failure to cancer-directed drugs. International research points to an important role of certain KLKs in female and male urogenital tract malignancies, in addition to cancers of the lung, brain, skin, head and neck, and the gastrointestinal tract. Regarding the female/male urogenital tract, remarkably, all of the KLKs are expressed in the normal prostate, testis, and kidney whereas the uterus, the ovary, and the urinary bladder are expressing a limited number of KLKs only. Most of the information regarding KLK expression in tumour-affected organs is available for ovarian cancer; all of the 12 KLKs tested so far were found to be elevated in the malignant state, depicting them as valuable biomarkers to distinguish between the normal and the cancerous phenotype. In contrast, for kidney cancer, a series of KLKs was found to be downregulated, while other KLKs were not expressed. Evidently, depending on the type of cancer or cancer stage, individual KLKs may show characteristics of a Janus-faced behaviour, by either expanding or inhibiting cancer progression and metastasis.

Replicability of findings is at the heart of any empirical science. The aim of this article is to move the current replicability debate in psychology towards concrete recommendations for improvement. We focus on research practices but also offer guidelines for reviewers, editors, journal management, teachers, granting institutions, and university promotion committees, highlighting some of the emerging and existing practical solutions that can facilitate implementation of these recommendations. The challenges for improving replicability in psychological science are systemic. Improvement can occur only if changes are made at many levels of practice, evaluation, and reward. Copyright © 2013 John Wiley & Sons, Ltd.

In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.

Background Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets. Methods Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n = 174). Results Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p = 0.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p = 0.0019) as well as with cathepsin B and D (p ≤ 0.0001) that are implicated in cell invasion and metastasis. Conclusions Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2663-9) contains supplementary material, which is available to authorized users.

Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-02.

The present research reports the results of three studies showing that individuals with a fragile self–concept in the domain of performance are particularly vulnerable to stereotype threat effects. Specifically, women who explicitly described themselves as rather mathematical but whose implicit self–concepts contradicted these claims were vulnerable to stereotype threat effects on mathematical performance. This effect was robust across three studies, independent of the subtleness or content of the stereotype threat manipulation. Additionally, it was shown that the effect was mediated by anxious worrying (Study 3). Copyright © 2012 John Wiley & Sons, Ltd.

Three studies investigated the correspondence between implicit and explicit self–concepts of intelligence and how that correspondence is related to performance on different intelligence tests. Configurations of these two self–concepts were found to be consistently related to performance on intelligence tests in all three studies. For individuals who self–reported high intelligence (high explicit self–concept), a negative implicit self–concept (measured with the Implicit Association Test) led to a decrease in performance on intelligence tests. For participants whose self–report indicated a low self–concept of intelligence, positive automatic associations between the self and intelligence had a similar effect. In line with a stress hypothesis, the results indicate that any discrepant configuration of self–concepts will impair performance. Importantly, the prediction of performance on intelligence tests by the self–concept of intelligence was shown to be independent of self–esteem (Study 3). Copyright © 2011 John Wiley & Sons, Ltd.

The resilience concept has often been criticized as simply reflecting the absence of neuroticism (i.e. vulnerability to stress and negative affectivity). Challenging this point of view, the aim of this study was to show that resilience could predict well-being in teachers above and beyond neuroticism. By contrast, we expected that resilience would not play the same role for non-teaching employees. Here, neuroticism should outperform resilience in predicting well-being, as resilience is supposed to be a special prerequisite for teachers, but not for non-teaching employees. One hundred seventy teachers and 183 non-teaching employees provided measures of resilience, neuroticism, and well-being. The aspects of well-being studied were general health perception, job satisfaction, exhaustion, and physical illness. Results revealed that among teachers, resilience contributed more to the prediction of general health perception than did neuroticism. Variance in job satisfaction was explained equally well by resilience and neuroticism. Physical illness and exhaustion were better predicted by neuroticism. In non-teachers, neuroticism predicted all outcomes better than did resilience. The results emphasize that resilience might be particularly important for the well-being of teachers, whereas for non-teachers, low neuroticism can be enough to maintain well-being. Specific occupational stress patterns experienced by teachers may explain these findings.

With two studies, we tested whether dispositional victim sensitivity involves one of two kinds of biased processing style: either a processing style in which unjust—but not just—information is processed more readily and accurately than neutral information or a processing style in which unjust and just information is processed preferentially over neutral information. In Study 1, victim sensitivity increased the speed with which participants resolved ambiguous sentence fragments in cases in which the resolution yielded an unjust connotation, as well as in cases in which the resolution yielded a just connotation, but not when the resolution was neutral with respect to justice. In Study 2, persons high in victim sensitivity displayed enhanced memory performance for both unjust and just information relative to neutral information over a 1–week retention interval. The results are consistent with the assumption that victim sensitivity is characterized by the activation potential and elaboration of both injustice and justice concepts. Our findings are important for the understanding of how the fear of being exploited among victim–sensitive persons shapes antisocial behaviour. Copyright © 2012 John Wiley & Sons, Ltd.