Identifying CBT non-response among OCD outpatients: A machine-learning approach

Objectives: Machine learning models predicting treatment outcomes for individual patients may yield high clinical utility. However, few studies tested the utility of easy to acquire and low-cost sociodemographic and clinical data. In previous work, we reported significant predictions still insufficient for immediate clinical use in a sample with broad diagnostic spectrum. We here examined whether predictions will improve in a diagnostically more homogeneous yet large and naturalistic obsessive-compulsive disorder (OCD) sample. Methods: We used sociodemographic and clinical data routinely acquired during CBT treatment of n = 533 OCD subjects in a specialized outpatient clinic. Results: Remission was predicted with 65% (p = 0.001) balanced accuracy on unseen data for the best model. Higher OCD symptom severity predicted non-remission, while higher age of onset of first OCD symptoms and higher socioeconomic status predicted remission. For dimensional change, prediction achieved r = 0.31 (p = 0.001) between predicted and actual values. Conclusions: The comparison with our previous work suggests that predictions within a diagnostically homogeneous sample, here OCD, are not per se superior to a more diverse sample including several diagnostic groups. Using refined psychological predictors associated with disorder etiology and maintenance or adding further data modalities as neuroimaging or ecological momentary assessments are promising in order to further increase prediction accuracy.Peer Reviewe

Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association

Bcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome.This work was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2033—Projektnummer 390677874, the DFG Priority Program SPP1601 “New Frontiers in Sensitivity in EPR Spectroscopy” (to E.B.), DFG BO 3000/5-1 (to E.B.), SFB958 – Z04 (to E.B.), DFG grant INST 130/972-1 FUGG (to E.B.). P.E.C. is supported by an Australian NHMRC fellowship (1079700

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity:PanCareLIFE dataset

Genetic association studies suggest a genetic predisposi- tion for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross- sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnos- tic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta- analyses to derive a more precise pooled estimate of the ef- fects of genes on the risk of hearing loss due to platinum treatment

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment

World ocean review: Mit den Meeren leben 6: Arktis und Antarktis – extrem, klimarelevant, gefährdet

Die sechste Ausgabe des „World Ocean Review“ (WOR) widmet sich der Arktis und Antarktis, diesen zwei extremen und ausgesprochen gegensätzlichen Regionen der Erde. Mit profunden Informationen zur Entstehungs- und Entdeckungsgeschichte bietet der WOR 6 ein tiefes Verständnis der Bedeutung der Pole für das Leben auf unserer Erde. Er zeigt zudem die zu beobachtenden Veränderungen in der Tier-und Pflanzenwelt und analysiert die zum Teil schon dramatischen Folgen, die der Klimawandel in diesen äußerst gefährdeten Regionen bewirkt

Comparing Construction and Study of Concept Maps - An Intervention Study on Learning Outcome, Self-Evaluation and Enjoyment Through Training and Learning

Concept maps are graphical tools for organizing and representing knowledge. They are recommended for biology learning to support conceptual thinking. In this study, we compare concept map construction (CM-c, i.e., creating concept maps) and concept map study (CM-s, i.e., observing concept maps). Existing theories and indirect empirical evidence suggest distinct effects of both formats on cognitive, metacognitive and emotional aspects of learning. We developed a CM-c training, a CM-s training, and a brief introduction to concept maps (control training) for junior high school students. We investigated effects on learning performance, concept map quality, cognitive load (cognitive effects), accuracy of self-evaluation (metacognitive effects) and enjoyment (emotional effects) of these trainings in a subsequent learning phase (CM-c learning vs. CM-s learning) in a quasi-experimental two-factorial study with 3 x 2 groups (N = 167), involving the factors training type and learning type. Results reveal that CM-c training increased learning performance and concept map quality. Effects of CM-c training on learning performance transferred onto learning with CM-s. Self-evaluation was slightly more accurate after CM-c training than CM-s training. Students reported moderate, and highly varying enjoyment during CM-c and CM-s learning. The superiority of CM-c over CM-s in learning performance and concept map quality probably lies in its characteristic of being an active learning strategy. We recommend practitioners to favor CM-c training over CM-s training, and foster students' active engagement and enjoyment

Brexit had no measurable effect on Irish exporters

We study the impact of the Brexit referendum on Irish exporters to the UK. The referendum triggered a sharp devaluation of the British pound vis-a-vis the euro and led to considerable uncertainty about future trade relations between the UK and the EU. Using administrative data on the universe of Irish exporters, we compare exporters with different levels of exposure to the UK market before the referendum. Our findings do not point to a significant effect of the referendum on Irish exporters. Over the period 2015-2021, the firms least exposed to the UK - but most internationalised otherwise - had considerably higher exit rates from exporting to the UK and from the market overall. They also saw greater declines in employment and sales compared to more exposed firms. We do not find significant differences for export volumes to the UK or elsewhere or for average wages. These findings are robust to controlling for a variety of firm characteristics