Search

The development of platforms for distributed analytics has been driven by a growing need to comply with various governance-related or legal constraints. Among these platforms, the so-called Personal Health Train (PHT) is one representative that has emerged over the recent years. However, in projects that require data from sites featuring different PHT infrastructures, institutions are facing challenges emerging from the combination of multiple PHT ecosystems, including data governance, regulatory compliance, or the modification of existing workflows. In these scenarios, the interoperability of the platforms is preferable. In this work, we introduce a conceptual framework for the technical interoperability of the PHT covering five essential requirements: Data integration, unified station identifiers, mutual metadata, aligned security protocols, and business logic. We evaluated our concept in a feasibility study that involves two distinct PHT infrastructures: PHT-meDIC and PADME. We analyzed data on leukodystrophy from patients in the University Hospitals of Tübingen and Leipzig, and patients with differential diagnoses at the University Hospital Aachen. The results of our study demonstrate the technical interoperability between these two PHT infrastructures, allowing researchers to perform analyses across the participating institutions. Our method is more space-efficient compared to the multi-homing strategy, and it shows only a minimal time overhead., (© 2024. The Author(s).)

The transition from a humid green Sahara to today's hyperarid conditions in northern Africa ~5.5 thousand years ago shows the dramatic environmental change to which human societies were exposed and had to adapt to. In this work, we show that in the 620,000-year environmental record from the Chew Bahir basin in the southern Ethiopian Rift, with its decadal resolution, this one thousand year long transition is particularly well documented, along with 20-80 year long droughts, recurring every ~160 years, as possible early warnings. Together with events of extreme wetness at the end of the transition, these droughts form a pronounced climate "flickering", which can be simulated in climate models and is also present in earlier climate transitions in the Chew Bahir environmental record, indicating that transitions with flickering are characteristic of this region., (© 2024. The Author(s).)

Background: The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy., Methods: Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways., Results: In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins., Conclusions: Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The complete gene encoding the 53-kDa protein derived from Trichinella spiralis was cloned and expressed using a baculovirus-based system. Characterization of a purified fusion protein consisting of the 53-kDa protein and the glutathione S-transferase protein showed unspecific reactivity with swine pre-immune serum in both enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Subsequently, a purified C-terminal 6xHis-tagged 53-kDa protein was used in an ELISA. The evaluation of the test using a negative serum panel showed a high specificity for the ELISA. Serum panels of pigs infected with T. spiralis of two independent experiments showed that pigs of one experiment were tested positive by the ELISA, whereas all sera of the second experiment were negative, indicating a low sensitivity of the ELISA. Furthermore, experimental evidence was found by using mass spectroscopy and Western blot analysis that the 53-kDa protein was not part of the excretory/secretory antigen of T. spiralis as shown in this study.

Infectious laryngotracheitis virus (ILTV), a member of the Alphaherpesvirinae, possesses several unique genes. One of them, UL0, encodes an abundantly expressed protein that accumulates in the nuclei of ILTV-infected cells. This study demonstrates that this protein is dispensable for in vitro virus replication and that UL0 deletion mutants exhibit only minor growth defects in cultured cells. The UL0 gene locus of ILTV was also used for insertion of foreign DNA sequences encoding enhanced GFP or haemagglutinin (HA), subtype H7, of a highly pathogenic avian influenza virus under the control of the human cytomegalovirus immediate-early gene promoter. Expression of foreign proteins was shown by (immuno)fluorescence tests and Western blot analyses. After experimental infection of chickens, UL0 deletion mutants proved to be attenuated when compared to both parental wild-type ILTV and an UL0 rescue mutant. Nevertheless, all animals immunized with UL0-negative ILTV were protected from clinical disease after subsequent infection with virulent ILTV. Furthermore, all animals immunized with HA-expressing ILTV survived a lethal challenge with H7 subtype avian influenza virus with minimal clinical signs. Thus, an UL0-negative and HA-expressing ILTV recombinant may be used as a bivalent live virus vaccine against ILT and fowl plague. Unlike inactivated influenza virus vaccines, HA-expressing ILTV recombinants should be suitable for mass application and would also permit serological discrimination between vaccinated and virus-infected animals in the field.

Background: In contrast to the acute effects of anabolic-androgenic steroid (AAS) abuse, the long-term risk profile of former long-term abusers (ExA) is less clear., Methods: Blood parameters of 32 male bodybuilders and powerlifters were studied. Fifteen ExA had not been abusing AAS for at least 12-43 months on average (mean dosage 700 mg for 26 weeks per year over 9 years), 17 athletes (A) were still abusing AAS (750 mg for 33 weeks per 8 years)., Findings: Hemoglobin (+5%), leucocytes (+33%) and platelets (+38%) were significantly higher in A. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher, cholinesterase activity (CHE) lower in A (65+/-55, 38+/-27 and 3719+/-1528U/l) compared to ExA (24+/-10, 18+/-11 and 6345+/-975U/l; each P<0.001) with normal values for gamma-glutamyl transpeptidase (gamma-GT) and bilirubin. ALT, AST and CHE correlated significantly with the extent (duration and weekly dosage, expressed as a point score) of AAS abuse in A (r=0.68, 0.57 and -0.62; each P<0.01). Total and LDL-cholesterol were similar, HDL-cholesterol was distinctly lower in A than in ExA (17+/-11 and 43+/-11 mg/dl; P<0.001) and correlated negatively with the extent of AAS abuse (r=-0.50; P<0.05). Testosterone and estradiol were significantly higher, while LH, FSH and the sexual-hormone-binding (SHB) protein were lower in A than in ExA (each P<0.001). Two ExA had testosterone levels below the normal range., Interpretation: The alterations in cell counts, HDL-cholesterol, liver function and most hormones of the pituitary-testicular axis induced by a long-term abuse of AAS were reversible after stopping the medication for over 1 year. In some ExA, an increased ALT activity and a depressed testosterone synthesis were found.