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Aim: Since reliable response predictors to platinum-based chemotherapy in ovarian cancer (OC) are scarce, we characterize NCALD as a predictive biomarker. Materials & methods: NCALD mRNA (n = 100) and protein (n = 102) expression was analyzed in OC samples and associated with patient outcome. A stable OC cell line knockdown was generated and cellular response to platinum was explored. Results: High NCALD mRNA and protein expression was significantly associated with longer overall patient survival (p = 0.037/0.002). Knockdown experiments revealed a significant association between cisplatin sensitivity and NCALD expression. Conclusion: Low NCALD expression was associated with reduced sensitivity to platinum-based chemotherapy. NCALD may be a new biomarker candidate to identify patients who might benefit from platinum-based chemotherapy.

In the last few years, plastic has become an issue of current interest as tremendous ecological effects from plastic littering have become visible. Taking the role of consumers into account, activities comprising purchasing decisions and political engagement are expected to help prevent plastic pollution. The goal of this study was to examine antecedents of three potential plastic reduction activities: purchasing, activism, and policy support. Based on well-established psychological models of pro-environmental behaviour (i.e. theory of planned behaviour, norm activation model), an online survey (N = 648) was administered and analysed via structural equation modelling. Results revealed that personal norms were a relevant predictor of all three intentions. Whereas sufficiency orientation and collective efficacy predicted only activism intention and policy support intention, perceived behavioural control was the strongest predictor of purchasing intentions. Regarding behaviour, people with high activism intentions and sufficiency orientation were more likely to choose a plastic-free incentive instead of the conventional shopping voucher. This study highlights psychological antecedents of plastic reduction. An integrated model showed that rational cost–benefit considerations as well as morality serve as drivers of reducing plastic consumption. Implications for the promotion of plastic-free consumption are discussed.

Patient characteristics of the whole breast cancer cohort used for CX3CL1 expression analysis (n=250)

CX3CL1 mRNA expression is associated with improved recurrence-free, distant-metastasis free, and overall survival in human breast cancer.

A crucial mode of action of trastuzumab is the labeling of HER2-positive (HER2+) tumor cells for the eradication by natural killer (NK) cells, a process called antibody-dependent cellular cytotoxicity (ADCC). However, despite widespread HER2 expression among cancer entities, only a fraction, with robust HER2 overexpression, benefits from trastuzumab therapy. ADCC requires both sufficient lymphocytic infiltration and close binding of the immune cells to the antibody-tagged tumor cells. We hypothesized that the chemokine CX3CL1 could improve both processes, as it is synthesized as a membrane-bound, adhesive form that is eventually cleaved into a soluble, chemotactic protein. Here, we show that CX3CL1 overexpression is a positive prognostic marker in breast cancer. CX3CL1 overexpression attracted tumor-suppressive lymphocytes, including NK cells, and inhibited tumor growth and lung metastasis in the syngeneic 4T1 breast cancer mouse model. In HER2+ SKBR3, MDA-MB-453, and HT-29 tumor cells, CX3CL1 overexpression increased NK cell–mediated cytotoxicity in vitro and acted synergistically with trastuzumab. Even though CX3CL1 did not further improve trastuzumab efficacy in vivo in the trastuzumab-sensitive MDA-MB-453 model, it compensated for NK-cell depletion and prolonged survival. In the HER2 low–expressing HT-29 model, however, CX3CL1 overexpression not only prolonged survival time but also overcame trastuzumab resistance in a partly NK cell–dependent manner. Taken together, these findings identify CX3CL1 as a feasible pharmacologic target to enable trastuzumab therapy in HER2 low–expressing cancers and render it a potential predictive biomarker to determine therapy responders.

Supplementary Data from DNA Methylation Markers Predict Outcome in Node-Positive, Estrogen Receptor-Positive Breast Cancer with Adjuvant Anthracycline-Based Chemotherapy

Supplementary Table S2 from Association of DNA Methylation of Phosphoserine Aminotransferase with Response to Endocrine Therapy in Patients with Recurrent Breast Cancer

To understand the biological basis of resistance to endocrine therapy is of utmost importance in patients with steroid hormone receptor–positive breast cancer. Not only will this allow us prediction of therapy success, it may also lead to novel therapies for patients resistant to current endocrine therapy. DNA methylation in the promoter regions of genes is a prominent epigenetic gene silencing mechanism that contributes to breast cancer biology. In the current study, we investigated whether promoter DNA methylation could be associated with resistance to endocrine therapy in patients with recurrent breast cancer. Using a microarray-based technology, the promoter DNA methylation status of 117 candidate genes was studied in a cohort of 200 steroid hormone receptor–positive tumors of patients who received the antiestrogen tamoxifen as first-line treatment for recurrent breast cancer. Of the genes analyzed, the promoter DNA methylation status of 10 genes was significantly associated with clinical outcome of tamoxifen therapy. The association of the promoter hypermethylation of the strongest marker, phosphoserine aminotransferase (PSAT1) with favorable clinical outcome was confirmed by an independent quantitative DNA methylation detection method. Furthermore, the extent of DNA methylation of PSAT1 was inversely associated with its expression at the mRNA level. Finally, also at the mRNA level, PSAT1 was a predictor of tamoxifen therapy response. Concluding, our work indicates that promoter hypermethylation and mRNA expression of PSAT1 are indicators of response to tamoxifen-based endocrine therapy in steroid hormone receptor–positive patients with recurrent breast cancer.

Contains fulltext : 290914.pdf (Publisher’s version ) (Open Access) BACKGROUND: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. METHODS: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500 mg/m(2)) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m(2) (FEC-Doc). Primary endpoint was disease-free survival (DFS). RESULTS: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1-94.8) with FEC-Doc and 93.7% (91.7-95.3) with FEC. Five-year-overall survival was 97.0% (95.4-98.0) for FEC-Doc and 96.6% % (94.9-97.8) for FEC. CONCLUSIONS: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.

INTRODUCTION The current study examined whether and how severe injustice such as a school attack threatens the belief in a just world (BJW). METHOD We collected longitudinal data on the BJW from adolescents in China who witnessed random school attacks on the news (N = 227). RESULTS Change analyses provided evidence that the BJW increased after witnessing severe injustice. Furthermore, we tested for moderating effects of buffer variables, such as life satisfaction and perceived social support, on change in the BJW. Findings showed that these variables buffered the threat to the BJW after observing unfairness. DISCUSSION We discuss these results in the context of justice motive theory and suggest implications for future research and practical implications.

The use of journal impact factors and other metric indicators of research productivity, such as the h-index, has been heavily criticized for being invalid for the assessment of individual researchers and for fueling a detrimental “publish or perish” culture. Multiple initiatives call for developing alternatives to existing metrics that better reflect quality (instead of quantity) in research assessment. This report, written by a task force established by the German Psychological Society, proposes how responsible research assessment could be done in the field of psychology. We present four principles of responsible research assessment in hiring and promotion and suggest a two-phase assessment procedure that combines the objectivity and efficiency of indicators with a qualitative, discursive assessment of shortlisted candidates. The main aspects of our proposal are (a) to broaden the range of relevant research contributions to include published data sets and research software, along with research papers, and (b) to place greater emphasis on quality and rigor in research evaluation.

Based on the assumption that disclosing explicit populist radical-right (PRR) attitudes and voting intentions for PRR parties may be inhibited by a social desirability bias, this paper aims at developing a measure for implicit populist attitudes (IAT) and at assessing its explanatory power for the prediction of PRR party support. Using data from a German online survey (N = 898), the populism-IAT is tested against corresponding direct measures of populist attitudes and anti-immigrant attitudes to predict voting propensity for the German PRR party Alternative für Deutschland (AfD). Results reveal that social desirability concerns indeed restrict the likelihood of reporting a high propensity of PRR vote; however, direct measures turn out as best predictors for self-reported voting intentions. Inconsistencies between implicit and explicit attitudes may indicate sensitivity to social (un-)desirability perceptions, when attitudes are displayed on the implicit but not on the explicit level. We find such incongruencies for 9% of our respondents regarding populist attitudes, and for 21% regarding anti-immigrant attitudes, indicating that the latter are considered even more undesirable. In light of our findings, we discuss the potential explanatory power of implicit attitudes for less deliberate forms of political behavior and the assumption of populist and anti-immigrant attitudes still being regarded as socially undesirable in Germany.

Studies complementing the assessment of symptoms right before (t1), right after therapy (t2), and at follow-up (t3) with an assessment of symptoms preceding the waiting period without intervention (t0) have revealed substantial t0–t1 changes. We discuss this phenomenon based on our own data and address the following questions: does it make sense to compare symptoms at the beginning of therapy (t1) with symptoms at the end of therapy (t2) or at follow-up (t3)? Or does it make more sense to use t0 instead of t1? We argue for the latter alternative based on the following reasons. (1) Symptom descriptions at t0 are realistic. (2) Expecting therapy success mitigates symptom descriptions at t1. (3) Security signals emitted from the therapy context also mitigate symptoms, especially anxiety, at t1. (4) Regression toward the mean reduces the validity of single occasion assessments. Controlling for regression requires two occasions of measurement with a short time interval at t0 (t01 and t02). It follows from this reasoning that therapy success should be evaluated using the t02–t2 and t02–t3 intervals. Single case evaluations require reliable critical differences. This will be illustrated using a concrete example. The validity of treatment evaluation can be increased via the elimination of non-pathological symptom scores. A simplified calculation of cut-off scores can facilitate applied treatment evaluation. Unspecific t0–t1 changes do not challenge therapy effects according to t1–t2 changes. Rather, they are part of the whole therapy process.

According to the congruence hypothesis, job and study satisfaction will be higher when individual interests and the respective environment (both conceptualised according to Holland’s RIASEC model) are congruent. As our target group were teacher students, all participants who did not intend to become a teacher or did not meet other inclusion criteria (e.g., no missing data on relevant variables) were removed from the sample, resulting in a final sample of N = 1171. Teacher students completed questionnaires on their vocational interests and their satisfaction with course content. To obtain an assessment of the environment (study majors), N = 166 lecturers were asked to rate their courses with respect to Holland’s RIASEC model. As previous findings have indicated that conclusions are influenced by the congruence measure that is used, we applied two different approaches. First, we computed the profile correlation between the individual interest profile and the environmental profile for each individual to measure congruence. Profile correlation scores were then correlated with satisfaction with course content scores. This correlation was significant (r = .21, p

Untersucht man Therapieverläufe nicht nur zwischen unmittelbarem Beginn und Beendigung, können Fortschritte be­reits zwischen Anmeldung und Beginn, noch ohne Intervention, aufgezeigt werden. Diese t0-t1-Veränderungen werden anhand eigener Befunde diskutiert: Ist der Vergleich Beginn (t1) – Ende der Therapie (t2) bzw. Katamnese (t3) sinnvoll, oder erfordert die angemessene Erfolgsbeurteilung nicht gerade Anmeldezeitpunkt t0? Wir plädieren für t0. (1) Anmeldung (t0) impliziert eine ausgeprägte, realistische Symptomschilde­rung, (2) positive Erwartungen zur erfolgreichen Behandlung verbessern Messwerte zu t1 (Aufnahme), (3) Aufnahmezeitpunkt t1 ist durch Sicherheitssignale der Klinik/der Behandler beeinflusst, Patientenratings – z.B. bei Angst – sind geringer (Kontextfaktoren), (4) Regression zur Mitte relativiert die Aussagekraft eines Einzelmesszeitpunkts: Hohe Messwerte dort fallen zu einem zweiten Zeitpunkt geringer aus. Um dies zu kontrollieren, müssen zu t0 (in geringem Abstand) 2 Messungen durchgeführt werden, nämlich t01 und t02. In der Praxis dient das Intervall t02–t2 zur geeigneten Erfolgsbeurteilung, aber auch t02–t3 sollte, wenn möglich, Auswertungsroutine sein. Einzelfallbeurteilungen erfordern die Berücksichtigung kritischer Differenzen, um messfehlerbereinigte Unterschiede zu sichern (Beispielerläuterung). Die Möglichkeit erweiterter Auswertung mittels Ausschluß nichtpathologischer Werte, der vereinfachten Auswertung mittels Cutoff-Bestimmung und einige Praxishinweise komplettieren die Arbeit. Unspezifische t0–t1-Veränderungen bedeuten keine Relativierung der Ergebnisse aktiver Intervention (t1–t2), sind vielmehr Bestandteil der Gesamttherapie.

This study examined pre-service teachers’ attitudes towards inclusion, posing research questions regarding the (1) relationship between attitudes and personality and (2) between attitudes and the u...

Die Arbeit des Fachkollegiums Psychologie sieht sich gegenwartig mit zwei Herausforderungen konfrontiert: 1) Die durchschnittliche Bearbeitungszeit eingereichter DFG-Antrage steigt und 2) die Forderquote von DFGAntragen ist in letzter Zeit merklich gesunken. Beide Probleme betreffen die DFG-Forderung generell (siehe z.B. „DFG-Forderquote sinkt rapide“, Forschung & Lehre, Heft 8, 2013, S. 608) und sind keineswegs spezifisch fur die Psychologie. Dies kann naturlich kein Grund sein, sich mit dem Status Quo zufriedenzugeben. Wir mochten deshalb in diesem Bericht Masnahmen darstellen, die aus unserer Sicht geeignet sind, den aktuellen Herausforderungen zu begegnen.1

Addressing the prevalent topic of plastic pollution, an intervention to break people’s consumption patterns was implemented. It was investigated if Lent could work as a ‘window of opportunity’ of h...

In Western samples, individuals differ systematically in the importance they assign to matters of justice and injustice, and dispositional Justice Sensitivity can be differentiated according to the perspectives of victim, observer, beneficiary, and perpetrator. In a cross-cultural comparison between the Philippines, Germany, and Australia ( N = 677 students), we investigated whether Justice Sensitivity can be equivalently described by these four perspectives, whether measurement instruments have invariant psychometric properties, and whether the psychological relevance of the Justice Sensitivity perspectives for cooperation behavior differs between these cultural contexts. The results of multigroup confirmatory factor analyses support weak measurement invariance and invariant associations between Justice Sensitivity perspectives and trust game decisions. Across cultures, victim sensitivity predicted reluctance to cooperate under threat of exploitation, and observer, beneficiary, and perpetrator sensitivities predicted cooperation under temptation. Our study extends insight into Justice Sensitivity to underresearched cultural contexts of urban and rural Philippines.

Zusammenfassung. In Studie 1 wurde die Validität des Fragebogens FEMOLA (Fragebogen zur Erfassung der Motivation für die Wahl des Lehramtsstudiums) durch Überprüfung der internen Struktur untersucht. Hierzu wurden anhand von Daten von N = 1467 Lehramtsstudierenden zwei in der Literatur vorgeschlagene Faktorenstrukturen verglichen, wobei sich zeigte, dass eine Lösung mit sieben Faktoren besser zu den Daten passte als die ursprünglich vorgeschlagene Lösung mit sechs Faktoren. Anschließend wurde die Messinvarianz über nach angestrebter Schulform gebildete Gruppen von Lehramtsstudierenden (Grundschule, Förderschule, Sekundarstufe I und Gymnasium) untersucht; hier konnte schwache Invarianz (gleiche Faktorladungen) festgestellt werden. In Studie 2 wurde anhand von Längsschnittdaten ( N = 442) untersucht, ob pädagogisches Wissen und selbst eingeschätzte Unterrichtskompetenz bei Lehramtsstudierenden anhand der Studienwahlmotivation und Zielorientierungen (Lernziele, Annäherungs- und Vermeidungs-Leistungsziele sowie Arbeitsvermeidung) vorhergesagt werden können. Dabei wurde mittels eines Strukturgleichungsmodells u.a. die Annahme geprüft, dass die Effekte der Studienwahlmotivation durch die Zielorientierungen vermittelt werden; der Einfluss von Intelligenz wurde kontrolliert. Erwartungskonform war die Studienwahl aus intrinsischer Motivation mit einer höheren Lernzielorientierung und einer niedrigeren Tendenz zur Arbeitsvermeidung verbunden; die Studienwahl aus extrinsischer Motivation hingegen mit höheren Ausprägungen von Annäherungs- und Vermeidungs-Leistungszielen sowie einer stärkeren Tendenz zur Arbeitsvermeidung. Die durch die Zielorientierungen vermittelten Pfade von den Studienwahlmotivations-Faktoren zu den Kriterien erwiesen sich jedoch weitgehend als nicht signifikant. Beide Kriterien waren zudem nur schwach miteinander korreliert und für Intelligenz ergab sich nur mit dem pädagogischen Wissen ein signifikanter Zusammenhang. Ursachen für diese Befunde und Abweichungen von vorliegenden Studien werden diskutiert.

Background: Clinical observations suggest that many patients with obsessive-compulsive disorder (OCD) suffer from severe feelings of guilt. These observations, which are consistent with psychoanalytic assumptions (overly strict super-ego), have rarely been subjected to systematic empirical investigation. Even cognitive approaches broach the issue of guilt as a facet of OCD only indirectly. The purpose of our research was to investigate whether more patients with OCD report feelings of guilt as compared to healthy controls. Patients and Method: One hundred individuals (34 males, 66 females) participated in our study. Fifty participants were OCD patients according to IDCL criteria and in stationary treatment. An additional sample of 50 participants consisted of healthy controls matched for age, gender, and job status. All participants were interviewed via Structured Clinical Interview for DSM-IV. Two scales measured proneness to guilt: (a) Trait Guilt Scale (TGS) and (b) Test of Self-Conscious Affect (TOSCA). A new guilt-inducing scenario-based test (SIT) including two scales (SIT 1, SIT 2) served the same purpose. The SIT was developed by the authors and uses scenarios derived from interviews with patients and experts. Finally, we assessed depression (Beck Depression Inventory; BDI) and obsessive compulsiveness (Yale-Brown Obsessive Compulsive Scale; Y-BOCS) in the OCD sample only. Results: Our data confirm stronger feelings of guilt among OCD patients as compared to matched controls. Patients and controls differed mostly on the TGS and the 2 SIT scales. TOSCA guilt scores did not differ reliably between patients and controls. Finally, as a side result, OCD patients reported elevated depression scores. Discussion: The results of this study suggest that feelings of guilt should receive more attention than previously in the treatment of OCD. OCD patients suffer not only from their compulsive cognitions and actions but also from feelings of guilt. Exposure therapy of OCD should be complemented by treatment components that specifically address feelings of guilt.

Hintergrund: Zwangspatient(inn)en leiden, wie klinische Beobachtungen zeigen, häufig unter starker Schuld, was sich auch mit frühen psychoanalytischen Annahmen (übermäßig hohes Über-Ich) deckt, bis heute aber nicht spezifisch empirisch untersucht wurde. Auch aktuelle kognitionspsychologische Ansätze fokussieren auf diese emotionale Seite des Zwangsgeschehens nur indirekt. Unser Anliegen be­stand daher in der Untersuchung, inwieweit Zwangspatient(inn)en ausgeprägteres Schulderleben aufweisen als Personen ohne Zwang. Patient(inn)en und Methode: 100 Proband(inn)en (34 männlich, 66 weiblich) nahmen an der Studie teil, davon 50 mit einer gesicherten, IDCL-bestätigten Diagnose Zwangsstörung während eines stationären Auf­enthalts, und 50 gematchte Proband(inn)en aus der Normalbevölkerung ohne Zwang. Alle Teilnehmenden erhielten eine Untersuchung mit dem Strukturierten klinischen Interview für DSM-IV (SKID); auch wurde die Depression (Beck Depression Inventory; BDI) erhoben. Mit den Patient(inn)en wurde sodann die Yale-Brown Obsessive Compulsive Scale (Y-BOCS) durchgeführt. Zu Schuld bearbeiteten alle Teilneh­menden 2 nichtklinische Instrumente: (a) Schuldinventar, Traitvariante, und (b) Test of Self-Conscious Affect (TOSCA). Darüber hinaus wurde für diese Studie der Schuldinduzie­rende Szenarien Test (SIT), basierend auf vorangegangenen Interviews mit Patient(inn)en und Expert(inn)en, entwickelt (2 Skalen) und von allen Proband(inn)en bearbeitet. Er­gebnisse: Die Annahme höheren Schulderlebens von Zwangspatient(inn)en wird durch die Daten gestützt. Sehr deutliche Unterschiede zwischen ihnen und den Kon­trollproband(inn)en fanden sich für Schuld (Trait) und die Skalen SIT 1 und SIT 2; der Schuldwert im TOSCA war dagegen unspezifisch. Als Nebenbefund sind hohe Depressions­werte bei den Zwangspatient(inn)en zu verzeichnen. Diskussion: Durch die Befunde wird nahegelegt, dass in der Behandlung von Patient(inn)en mit einer Zwangserkrankung stärker als bisher das Schulderleben thematisiert werden sollte. Die Patient(inn)en leiden neben ihren Zwangshandlungen und -gedanken stark darunter. Leitliniengerechte Behandlung via Expositionen sollte insofern ergänzt werden um spezifische Behandlungsabschnitte zu Schuld und ­Schuldverarbeitung.

A crucial mode of action of trastuzumab is the labeling of HER2-positive (HER2+) tumor cells for the eradication by natural killer (NK) cells, a process called antibody-dependent cellular cytotoxicity (ADCC). However, despite widespread HER2 expression among cancer entities, only a fraction, with robust HER2 overexpression, benefits from trastuzumab therapy. ADCC requires both sufficient lymphocytic infiltration and close binding of the immune cells to the antibody-tagged tumor cells. We hypothesized that the chemokine CX3CL1 could improve both processes, as it is synthesized as a membrane-bound, adhesive form that is eventually cleaved into a soluble, chemotactic protein. Here, we show that CX3CL1 overexpression is a positive prognostic marker in breast cancer. CX3CL1 overexpression attracted tumor-suppressive lymphocytes, including NK cells, and inhibited tumor growth and lung metastasis in the syngeneic 4T1 breast cancer mouse model. In HER2+ SKBR3, MDA-MB-453, and HT-29 tumor cells, CX3CL1 overexpression increased NK cell–mediated cytotoxicity in vitro and acted synergistically with trastuzumab. Even though CX3CL1 did not further improve trastuzumab efficacy in vivo in the trastuzumab-sensitive MDA-MB-453 model, it compensated for NK-cell depletion and prolonged survival. In the HER2 low–expressing HT-29 model, however, CX3CL1 overexpression not only prolonged survival time but also overcame trastuzumab resistance in a partly NK cell–dependent manner. Taken together, these findings identify CX3CL1 as a feasible pharmacologic target to enable trastuzumab therapy in HER2 low–expressing cancers and render it a potential predictive biomarker to determine therapy responders.

Stereotypes influence teachers’ perception of and behaviour towards students, thus shaping students’ learning opportunities. The present study investigated how 315 Australian pre-service teachers’ ...

A crucial mode of action of trastuzumab is the labeling of HER2-positive (HER2

Background Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4–7) strongly increase the malignancy of ovarian cancer cells. Deciphering their downstream effectors, we aimed at finding new potential prognostic biomarkers and treatment targets for ovarian cancer patients. KLK4–7-transfected (OV-KLK4–7) and vector-control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select differentially regulated factors. Methods With three independent approaches, PCR arrays, genome-wide microarray and proteome analyses, we identified 10 candidates (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine differential protein expression, we performed western blot analyses, immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19, KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues. Results We demonstrated that KLK4–7 clearly regulates expression of MSN, KRT19, KRT7 and JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein expression of the top-upregulated effectors, MSN and KRT19, was investigated by immunohistochemistry in patients afflicted with serous ovarian cancer and related to KLK4–7 immunoexpression. Significant positive associations were found for KRT19/KLK4, KRT19/KLK5 and MSN/KLK7. Conclusion These findings imply that KLK4–7 exert key modulatory effects on other cancer-related genes and proteins in ovarian cancer. These downstream effectors of KLK4–7, MSN and KRT19 may represent important therapeutic targets in serous ovarian cancer.

Despite the broad consensus in psychology that human behaviour is influenced by the interaction between characteristics of the person and characteristics of the situation, not much is known about the precise shape of this person–situation (P × S) interaction. To address this issue, we introduce and test the nonlinear interaction of person and situation (NIPS) model. The NIPS model can be applied to explain contradictory research results, offers a more accurate prediction of behaviour, and can be applied to any trait. In three studies and with three different analytical approaches, we test the NIPS model and its implications. In the pre–study, we test whether variability in participants’ behaviour is smaller in extreme aggression–provoking and jealousy–inducing situations than in moderate situations, suggesting the effect of ‘strong’ situations at the extremes of the situation continuum. In Studies 1 and 2, we test the nonlinear relation between person and situation variables in predicting behaviour in within–subject designs and provide support for the predictions of the NIPS model. Future lines of research with the NIPS model are discussed. Copyright © 2018 European Association of Personality Psychology

Gene expression of a variety of the 15 members of the KLK serine protease family is dysregulated in ovarian cancer. We aimed at determining the clinical relevance of KLK13 and KLK14 mRNA expression in tumor tissues of a homogeneous patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO stage III/IV). mRNA expression levels of KLK13 and KLK14 were assessed by quantitative PCR in tumor tissue of 91 patients and related with clinical factors and patients’ outcome. There was no significant association of KLK13 and KLK14 mRNA expression with the clinical factors ascitic fluid volume or residual tumor mass. In univariate Cox regression analysis, elevated KLK13 mRNA levels were significantly linked with shorter progression-free (PFS; hazard ratio [HR] = 1.97, P = 0.020) and overall survival (OS; HR = 1.81, P = 0.041). High KLK14 mRNA levels were significantly associated with prolonged PFS (HR = 0.44, P = 0.017) and showed a trend towards significance for OS (HR = 0.55, P = 0.070). In multivariable analysis, including the factors age, residual tumor mass, ascitic fluid volume, KLK13, and KLK14, both KLKs, apart from residual tumor mass, remained statistically independent predictive markers: patients with high KLK13 mRNA expression levels displayed a more than twofold increase risk for shorter PFS (HR = 2.14, P = 0.020) as well as OS (HR = 2.05, P = 0.028), whereas elevated KLK14 mRNA values were found to be significant for both, prolonged PFS (HR = 0.36, P = 0.007) and OS (HR = 0.46, P = 0.037). These results indicate that in advanced high-grade serous ovarian cancer KLK13 may become proficient for tumor-supporting functions, whereas KLK14 may have adopted tumor-suppressing activity.

Background: Breast cancer patients at high risk for recurrence are treated with anthracycline-based chemotherapy, but not all patients do equally benefit from such a regimen. To further improve therapy decision-making, biomarkers predicting outcome are of high unmet medical need. Methods: The percent DNA methylation ratio (PMR) of the promoter gene coding for the Paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time polymerase chain reaction (PCR) test. The multicenter study was conducted in routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue from 205 lymph node-positive breast cancer patients treated with adjuvant anthracycline-based chemotherapy. Results: The cut-off for the PITX2 methylation status (PMR = 12) was confirmed in a randomly selected cohort (n = 60) and validated (n = 145) prospectively with disease-free survival (DFS) at the 10-year follow-up. DFS was significantly different between the PMR ≤ 12 versus the PMR > 12 group with a hazard ratio (HR) of 2.74 (p < 0.001) in the validation cohort and also for the patient subgroup treated additionally with endocrine therapy (HR 2.47; p = 0.001). Conclusions: Early-stage lymph node-positive breast cancer patients with low PITX2 methylation do benefit from adjuvant anthracycline-based chemotherapy. Patients with a high PITX2 DNA methylation ratio, approximately 30%, show poor outcome and should thus be considered for alternative chemotherapy regimens.

What are the long-term effects of justice and injustice in school? This longitudinal study examined the bidirectional relationships of classroom justice with students’ behavioral problems, well-being, and joy of learning. Using systematic observation on the singlechild level, teachers and external observers made high and low inference justice ratings of 245 primary school students. The justice ratings measured two aspects of classroom justice: pedagogical practices and teacher–child interactions. Results indicate that there is a bidirectional relationship between behavioral problems and classroom justice. On the one hand, behavioral problems led to a decrease in the respectfulness of teacher–child interactions as rated by the teachers. On the other hand, just pedagogical practices as rated by external observers led to decreases in the children’s behavioral problems but also in their joy of learning. There was a negative effect of justice sensitivity on joy of learning. These results might be due to teachers’ adaptiveness. Teachers might especially focus their attention and efforts on the children who seem to need them the most, for instance, children with a low joy of learning or behavioral problems. These results might be used to sensitize teachers and school developers to the importance of classroom justice.

Although many motivational theories have emphasized that person- and situation-based aspects should be recognized simultaneously when explaining actual learning behavior, not much is known about the occurrence of state goals. The model of adaptive learning (Boekaerts & Niemivierta, 2000) proposes that state goals are influenced by trait goals, perceptions of the situation (i.e., appraisals), and interactions between trait goals and appraisals. Nevertheless, empirical evidence for this model is scarce. The present study aimed to overcome this research deficit by integrating trait goals and appraisals as well as their interactions in explaining state goals in authentic learning episodes. As suggested by Boekaerts and Niemivierta (2000), we adopted a multiple-goal approach and included achievement goals (i.e., mastery, performance-approach, and performance-avoidance goals) as well as well-being goals (i.e., affiliation and work-avoidance goals). They outlined the meaning of perceived relevance and autonomy for learning behavior. Therefore, we included both appraisals in our study. Using longitudinal data with one trait and two state measurements (N = 542), we applied structural equation modeling to test three different effect models with latent variables: an additive effect model, a reactive effect model, and an interaction effect model. Our data did not fit the reactive effect model: Trait goals did not impact appraisals. The joint influence of trait goals and appraisals on state goals was not unitary but multiform: Additive and multiplicative relations between trait goals and appraisals explained the occurrence of state goals. State goals are important predictors of proximal learning behavior. Thus, these results are important for theory development and for practitioners.

This study investigated the relationship between teachers’ beliefs about gifted students’ characteristics compared to students with average-ability and the teachers’ motivation (i.e., enthusiasm, s...

There has been a limited focus on the construal of justice judgments in contexts where norms are potentially conflicting, despite the relevance of norms in justice research. The present study aimed to close this gap by looking at the case of favoritism in Jordan where such conflicting norms are highly salient. A qualitative approach was chosen to facilitate ample exploration of the contextual complexities of the study’s setting. The main data basis were 22 problem-centered interviews conducted with managers and employees in Jordanian non-profit organizations. Data collection and analysis were guided by grounded theory methodology. The resulting theoretical framework of motivated moralization demonstrated that people flexibly construed favoritism as either unjust or justifiable to pursue a number of goals. Instead of relying on a single norm or standard, people strategically adopted the norms that were best suited to substantiate or legitimize a desired position. The norm conflict surrounding favoritism in Jordan facilitated this process by providing a selection of fitting norms for appropriation.

Cathepsin B (CTSB) is a lysosomal cysteine protease that has been linked to the progression of breast cancer, for example by activation of other proteases and tumor-promoting cytokines, thereby supporting tumor invasion and metastasis. Previously, it was shown that CTSB cleaves and inactivates C-X-C motif chemokine receptor 3 (CXCR3) chemokines. As CXCR3 ligands have been demonstrated to induce proteases in cancer cells, the present study hypothesized that they may also affect CTSB in breast cancer cells. The results demonstrated that the human breast cancer tumor cell lines MCF-7 and MDA-MB-231 express the CXCR3 splice variants A and B and CTSB. Upon binding to CXCR3, the two chemokine ligands C-X-C motif chemokine ligand (CXCL) 9 and CXCL10 trigger upregulation of CTSB in these breast cancer cells, whereas the CXCR3-B-specific ligand CXCL4 has no such effect, suggesting the involvement of CXCR3-A in the regulation of CTSB. In early-stage human breast cancer specimens (n=81), overexpression of CXCR3 is associated with statistically significant poorer overall survival, independent of lymph node status, tumor size and nuclear grading (hazard ratio=1.99; 95% confidence interval=1.00–3.97; P=0.050). In conclusion, the data from the current study propose a so far unknown mechanism by which breast cancer cells may exploit tumor-suppressive chemokines to enhance their invasiveness and reduce immune cell infiltration by the degradation of these chemokines. This mechanism may support the established unfavorable prognostic feature of CXCR3 expression in breast cancer.

Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor and stroma cells. In this patient cohort, elevated stroma cell KLK4 expression, but not tumor cell KLK4 expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26,p=0.001) and multivariable analysis (hazard ratio: 2.12,p