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Abstract: Little is known about pathogenesis – and especially about involvement of CD8+ T-cells – in late-onset myasthenia gravis (LOMG). Remarkably, outstanding CD8+ TCRVβ-subset expansions were found in 64% and 72% of recent onset LOMG or thymoma-associated MG (vs. 16% with early-onset MG (p <0.0002); 21% in older controls (p <0.001)). In LOMG, ~25% of the expanded cells initially showed a naïve CD62L+hi/CD45RA+ recent thymic emigrant (RTE)-like phenotype. These expansions associated significantly with IgG antibodies against cytomegalovirus (p <0.036), IL-12 and/ or IFN-α2 (p <0.03). The CD8+ TCRVβ expansions were stable over 5years, but RTE markers declined. [Copyright &y& Elsevier]

Abstract: We have investigated the structure and growth of Pd and BaO containing nanoparticles sequentially co-deposited on an ordered Al2O3/NiAl(110) by scanning tunneling microscopy (STM), and their interaction with CO and NO2 by infrared reflection absorption spectroscopy (IRAS). Ba deposition and subsequent oxidation result in Ba x Al2 y O x +3 y nanoparticles being formed which are characterized by high particle densities and nucleation both on regular terraces and at oxide defects. In contrast, Pd interaction with the model support is weaker and preferential nucleation occurs mainly at rotational domain boundaries and to a lesser extent at anti-phase domain boundaries. For subsequent co-deposition of Pd on preformed Ba x Al2 y O x +3 y /Al2O3/NiAl(110), Pd nucleates at the Ba x Al2 y O x +3 y nanoparticles and covers them. The reverse deposition sequence, i.e. subsequent Ba co-deposition and oxidation on preformed Pd/Al2O3/NiAl(110), leads to formation of small isolated Ba x Al2 y O x +3 y nanoparticles without contact to Pd, together with large Pd crystallites modified by Ba x Al2 y O x +3 y . The present results provide control over the degree of interaction between metal nanoparticles and oxide nanoparticles on a well-defined model catalyst and thus allow us to study effects related effects on the reactivity and catalytic behavior. [Copyright &y& Elsevier]

Background and Objective: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks., Materials and Methods: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets. Finally, participants rated the risks according to severity, level of evidence and prevalence., Results: Significant discrepancies between anticipated donor risks and the collected data were found. Furthermore, many participants reported that national data on adverse reactions in donors of stem cells, gametes, embryos and tissues were not routinely collected and/or available., Conclusions: These findings indicate that there is a need to further develop and standardize donor vigilance in Europe and to include long-term risks to donors, which are currently underreported, ensuring donor health and securing the future supply of SoHO., (© 2020 International Society of Blood Transfusion.)

Background and Objective: Donor selection criteria (DSC) are a vital link in the chain of supply of Substances of Human Origin (SoHO) but are also subject to controversy and differences of opinion. Traditionally, DSC have been based on application of the precautionary principle., Materials and Methods: From 2017 to 2020, TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors), a European research project, aimed to identify discrepancies between current DSC by proposing a standardized risk assessment method for all SoHO (solid organs excluded) and all levels of evidence., Results: The current DSC were assessed using a modified risk assessment method based on the Alliance of Blood Operators' Risk-based decision-making framework for blood safety. It was found that with limited or diverging scientific evidence, it was difficult to reach consensus and an international standardized method for decision-making was lacking. Furthermore, participants found it hard to disregard their local guidelines when providing expert opinion, which resulted in substantial influence on the consensus-based decision-making process., Conclusions: While the field of donation-safety research is expanding rapidly, there is an urgent need to formalize the decision-making process regarding DSC. This includes the need for standardized methods to increase transparency in the international decision-making process and to ensure that this is performed consistently. Our framework provides an easy-to-implement approach for standardizing risk assessments, especially in the context of limited scientific evidence., (© 2020 International Society of Blood Transfusion.)

Human B cell activating factor (TNFSF13B, BAFF) is a tumor necrosis factor superfamily member. Binding its unique receptor (TNFRSF13C, BAFF-R) mediates gene expression and cell survival in B cells via activation of NFκB pathway. Furthermore, there is data indicating a role in T cell function. A functionally inhibitory isoform (ΔBAFF) resulting from the deletion of exon 3 in the TNFSF13B pre-RNA has already been reported. However, data on the complexity of post-transcriptional regulation is scarce. Here, we report molecular cloning of nine TNFSF13B transcript variants resulting from alternative splicing of the TNFSF13B pre-mRNA including BAFFX1. This variant is characterized by a partial retention of intron 3 of the TNFSF13B gene causing the appearance of a premature stop codon. We demonstrate the expression of the corresponding BAFFX1 protein in Jurkat T cells, in ex vivo human immune cells and in human tonsillar tissue. Thereby we contribute to the understanding of TNFSF13B gene regulation and reveal that BAFF is regulated through a post-transcriptional mechanism to a greater extent than reported to date., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Both theories and cutting-edge research highlight the dynamic nature of personality and personality pathology, thereby posing significant challenges for an exclusively between-person, trait-based approach to personality assessment. In a series of 3 studies, we explored the viability of integrating within-person, dynamic aspects into clinical personality assessment by means of daily dairy methods. In the 1st study, 314 students filled out a 73-item questionnaire capturing daily behaviors and situation experiences across 7-10 consecutive days. We used multilevel exploratory factor analyses to construct a shortened version, the Personality Dynamics Diary (PDD). In the 2nd study, the PDD was applied in a sample of 77 psychotherapy inpatients across 40 days, on average. In the 3rd study, 35 psychotherapy outpatients as well as their therapists judged the clinical utility of a smartphone version of the PDD. Taken together, we were able to construct a relatively brief self-report measure that assesses major dimensions of within- and between-person differences of situations and behaviors in daily life with acceptable reliability. Application in clinical samples provided further evidence for the reliability, validity, and clinical utility of the PDD but also highlighted possible obstacles in clinical practice as well as the need for further replication and refinement. We conclude that daily diary methods have the potential to integrate within- and between-person approaches to personality assessment. By applying measures like the PDD, clinicians may gain insight into the psychological mechanisms that give rise to, and maintain, a person's maladaptive dispositions and ultimately find individualized leverage points for targeted therapeutic interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly recognized as a key correlate of cognitive and memory decline in Alzheimer patients. We hypothesized that functional synaptic disconnections within cortical columnar microcircuits by pathological β-amyloid accumulation, rather than cell death, initially causes the cognitive impairments. During development of cortical β-amyloidosis with still few plaques in the transgenic 5xFAD mouse model single cell resolution mapping of neuronal thallium uptake revealed that electrical activity of pyramidal cells breaks down throughout infragranular cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of pyramidal cell activity, indicating pyroglutamate-modified forms, potentially mixed oligomers of Aβ are contributing to neuronal impairment. Laminar investigation of cortical circuit dysfunction with current source density analysis identified an early loss of excitatory synaptic input in infragranular layers, linked to pathological recurrent activations in supragranular layers. This specific disruption of normal cross-laminar cortical processing coincided with a decline of contextual fear learning., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To study the influence of a regional collaboration in epithelial ovarian cancer care on staging procedures, debulking results, and survival., Methods: In an effort to optimize epithelial ovarian cancer treatment, a regional collaboration was introduced in the Netherlands in 2000. Gynecologic oncologists from the university center conducted surgery in community hospitals when ovarian cancer was considered based on the risk of malignancy index or clinical suspicion. The National Cancer Registry registered 1,554 patients with epithelial ovarian cancer diagnosed in 11 participating Dutch hospitals between 1996 and 2010. Surgical procedures were compared during three periods (1996-1999, 2000-2004, and 2005-2009). Log-rank tests compared Kaplan-Meier survival curves of progression-free and overall survival before (1996-2000) and during the start of the collaboration (2001-2005)., Results: Staging was adequate for 139 patients (23.0%) before collaboration, and this proportion increased during the study periods to 32.1% and 62.1% (P<.01), when gynecologic oncologists more often staged cancer in patients (36.7% compared with 54.7% and 80.6%; P<.01). For 1,197 patients with advanced stage disease (stage IIb or greater), the proportion of debulking procedures with an optimal (residual volume less than1 cm) as well as a complete result (no residuals) increased during the 14-year study period from 57.4% to 76.5% (P<.01) and from 24.1% to 43.4% (P<.01), respectively. Survival rates were similar before and during the start of the collaboration. In multivariable analysis, the treatment variables completeness of debulking, chemotherapy, and gynecologic oncologist attendance were independent prognostic factors for overall survival, as were age, stage, and tumor grade., Conclusions: After regional collaboration, gynecologic oncologists attended more surgeries and surgical outcomes improved, but progress in survival could not be demonstrated. Regional collaboration improved care for ovarian cancer patients., Level of Evidence: II.

Towards a better understanding of novel catalytic materials consisting of supported noble metal catalysts modified by an ionic liquid (IL) film, we have performed a study under ultrahigh-vacuum (UHV) conditions. The model surface consists of Pd nanoparticles grown in UHV on an ordered alumina film on NiAl(110). Thin films of the room temperature IL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][Tf(2)N] are deposited onto this surface by means of physical vapor deposition (PVD). The interaction of the IL with clean and CO-covered Pd/Al(2)O(3)/NiAl(110) at 300 K and the thermal behavior of the deposited IL films on Pd/Al(2)O(3)/NiAl(110) are investigated by time-resolved infrared reflection absorption spectroscopy (TR-IRAS) and X-ray photoelectron spectroscopy (XPS). At 300 K, the IL adsorbs molecularly both onto the Pd particles and onto the alumina. The IR spectra suggest that the [Tf(2)N](-) anions interact with Pd sites preferentially via the sulfonyl groups. CO pre-adsorbed on the Pd particles is partially displaced by the IL, even at 300 K, and only the part of CO adsorbed onto hollow sites on (111) facets of the Pd particles remains in place. Upon heating to temperatures higher than the desorption temperature of the IL (>400 K), molecular desorption of the IL competes with decomposition. The decomposition products, atomic species and small fragments, remain preferentially adsorbed onto the Pd nanoparticles and strongly modify their surface properties. Most of the decomposition products originate from the [BMIM](+) cations, whereas the [Tf(2)N](-) anions desorb for the most part.