Cross-cultural neuropsychological assessment in Europe: Position statement of the European Consortium on Cross-Cultural Neuropsychology (ECCroN)

Over the past decades European societies have become increasingly diverse. This diversity in culture, education, and language significantly impacts neuropsychological assessment. Although several initiatives are under way to overcome these barriers - e.g. newly developed and validated test batteries - there is a need for more collaboration in the development and implementation of neuropsychological tests, such as in the domains of social cognition and language. To address these gaps in cross-cultural neuropsychological assessment in Europe, the European Consortium on Cross-Cultural Neuropsychology (ECCroN) was established in 2019. ECCroN recommends taking a broad range of variables into account, such as linguistic factors, literacy, education, migration history, acculturation and other cultural factors. We advocate against race-based norms as a solution to the challenging interpretation of group differences on neuropsychological tests, and instead support the development, validation, and standardization of more widely applicable/cross-culturally applicable tests that take into account interindividual variability. Last, ECCroN advocates for an improvement in the clinical training of neuropsychologists in culturally sensitive neuropsychological assessment, and the development and implementation of guidelines for interpreter-mediated neuropsychological assessment in diverse populations in Europe. ECCroN may impact research and clinical practice by contributing to existing theoretical frameworks and by improving the assessment of diverse individuals across Europe through collaborations on test development, collection of normative data, cross-cultural clinical training, and interpreter-mediated assessment

Inhibition Mechanism and Model of an Angiotensin I-Converting Enzyme (ACE)-Inhibitory Hexapeptide from Yeast (Saccharomyces cerevisiae)

Angiotensin I-converting enzyme (ACE) has an important function in blood pressure regulation. ACE-inhibitory peptides can lower blood pressure by inhibiting ACE activity. Based on the sequence of an ACE-inhibitory hexapeptide (TPTQQS) purified from yeast, enzyme kinetics experiments, isothermal titration calorimetry (ITC), and a docking simulation were performed. The hexapeptide was found to inhibit ACE in a non-competitive manner, as supported by the structural model. The hexapeptide bound to ACE via interactions of the N-terminal Thr1, Thr3, and Gln4 residues with the residues on the lid structure of ACE, and the C-terminal Ser6 attracted the zinc ion, which is vital for ACE catalysis. The displacement of the zinc ion from the active site resulted in the inhibition of ACE activity. The structural model based on the docking simulation was supported by experiments in which the peptide was modified. This study provides a new inhibitory mechanism of ACE by a peptide which broads our knowledge for drug designing against enzyme targets

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 x 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the H LA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk

<em>HLA-DQA1-HLA-DRB1</em> variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

Functional dependencies (FDs) specify the intended data semantics while violations of FDs indicate deviation from these semantics. In this paper, we study a data cleaning problem in which the FDs may not be completely correct, e.g., due to data evolution or incomplete knowledge of the data semantics. We argue that the notion of relative trust is a crucial aspect of this problem: if the FDs are outdated, we should modify them to fit the data, but if we suspect that there are problems with the data, we should modify the data to fit the FDs. In practice, it is usually unclear how much to trust the data versus the FDs. To address this problem, we propose an algorithm for generating non-redundant solutions (i.e., simultaneous modifications of the data and the FDs) corresponding to various levels of relative trust. This can help users determine the best way to modify their data and/or FDs to achieve consistency